Utilizing nanomaterials for cancer treatment and diagnosis: an overview

Cancer refers to the condition characterized by abnormal, uncontrolled, and unregulated cell division and growth within the body. As the second leading cause of mortality globally, cancer remains a significant public health concern. The World Health Organization reported 9.6 million fatalities and approximately 18.1 million new cases of cancer in 2018 [1]. Projections suggest that by 2040, there will be 29.5 million new cancer cases annually, with 16.4 million deaths attributed to cancer-related causes [2]. These statistics highlight cancer’s high mortality rate and its profound impact on individuals and families, burdening them with economic challenges and the long-term effects of treatment. Consequently, efforts in cancer detection, treatment, and prevention are essential.

Diagnosis commonly relies on tumour markers, biopsy and histological examination, endoscopy, blood tests, and radiographic techniques such as X-rays, CT scans, and MRIs. Traditional treatments include surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, and hormone therapy. While these methods are effective in cancer detection and treatment, they come with significant drawbacks, including hair loss, fatigue, skin disorders, gastrointestinal issues, bone marrow suppression, and a high risk of recurrence. Immunotherapeutic agents have shown promise in treating primary cancers, preventing distant metastasis, and reducing cancer recurrence rates [3]. However, challenges such as autoimmune disorders and multi-drug resistance remain [4], and immunotherapy is less effective against solid tumours compared to lymphomas [5], partly due to the atypical extracellular matrix (ECM) produced by these tumours, which hinders immune cell penetration [6].

Given these challenges, there is a growing demand for novel strategies and the development of alternative, precise, and effective cancer treatments. Research has shown that nanoparticles (NPs) can address many limitations of conventional therapies. Their exceptional physical, chemical, and biological properties make NPs ideal for cancer diagnosis and treatment [7, 8].

To realize why nanoparticles are favourable to be used as therapeutic agents to address cancer treatment, there is a need to look into the mechanisms of action of the nanoparticles in brief. The fundamental mechanism involves initiation of programmed cell death otherwise known as the ‘cell apoptosis’, and there are several ways in such actions are initiated. The method that has received the most research attention is reactive oxygen species (ROS)-mediated apoptosis. Other mechanisms that cause regulated death of malignant cells include immunological interventions, site-specific cytotoxicity, transcription inhibition, and up- and down-regulation of proteins.

2.1 Generation of ROS

One of the fundamental modes of action that has been researched in relation to nanoparticle-induced cytotoxicity is ROS-induced apoptosis. In general, ROS has both pro- and anti-apoptotic actions. Processes like obstruction to cell cycle, apoptosis, and necrosis are the results of the pro-apoptotic effect of ROS, whereas the anti-apoptotic effect of ROS occurs when apoptosis is inhibited and cell invasion, proliferation, and metastasis are encouraged [9]. Thus, it acts as a double-edged sword. ROS-mediated apoptosis can be induced by proteins. Most cancer types lose fragile histidine triad (FHIT) proteins, but when they are recovered, they can trigger apoptosis. Since nanoparticles have a larger surface area and hence are more reactive, they are more effective at inducing apoptosis. This leads to an excessive production of ROS. Several nanoparticles have already been studied to observe the ROS effect. Silver nanoparticles encapsulated in polysaccharides were discovered to produce high levels of ROS, leading to cell death mainly through autophagy and prolonged apoptosis [10] as shown in Fig. 1. Increased oxidative stress in cells leads to the release of inflammatory intermediates, causing DNA and protein damage, ultimately resulting in cytotoxicity with substantial apoptotic effects. [11].

Diagram illustrating the extracellular and intracellular origins of reactive oxygen species (ROS) production. [12]

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2.2 Regulation of proteins

A state in which, in either normal or oxidative stress conditions, the cells mimic a cellular response to any external or internal stimulus is represented by the up- and down-regulation of proteins. Proteins are controlled during stressful situations in order to reconfigure metabolic and signalling pathways. This causes changes in the membrane turnover, which in turn affect the cell cycle progression and proliferation and cause apoptosis and hence tumour suppression [13]. In the research cell line HT-29, copper oxide nanoparticles (CuO-NPs) have the ability to cause programmed cell death by down-regulating the apoptotic regulatory proteins (Bcl2 and BclxL) [14]. Potentially, gold nanoparticles could impair pancreatic cancer cells’ ability to migrate and form colonies by reducing the phosphorylation of important components which would then restore the cancer cells’ chemoresistance. Role of nanoparticles in protein regulation is shown in Fig. 2.

Role of nanoparticles in protein regulation [15]

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2.3 Radiation therapy

Radioisotopes for their elimination via use of extracellular proteins called opsonin reduces the therapeutic impact of these radioisotopes as these particles are allowed to leave the circulation quickly. Here nanoparticles can play miraculous role as it is possible to encapsulate the radioactive molecules in the nano-crystalline matrices which will not only reduce the risk of radiation posed to neighbouring cells, but also enable the effective retention of the radioisotopes in the matrices such that it can reach the target and extend the period of efficient exposure to the malignant cells thereby causing their apoptosis. By leveraging the enhanced permeability and retention (EPR) effect, the use of nanoparticles containing a radioactive core can reduce opsonization and enhance the longevity of the therapeutic nanoparticle [16]. Utilising nanoparticles as radiosensitizers to selectively target tumour cells during radiation therapy will enhance the efficacy of X-ray radiation therapy against cancer cell lines. A study observed that radioactive palladium gold nanoparticles were effectively trapped in prostate cancer tumours for an extended period, resulting in a dose-dependent suppression of tumour growth. In addition, studies have demonstrated that lipophilic nanoparticles containing bismuth can significantly improve the effectiveness of X-ray radiation therapy in breast cancer cells [17]. These nanoparticles achieve this by causing a dose-dependent suppression of cell proliferation in breast cancer cell lines [18]. Mechanism of action of nanoparticles in radiation therapy is shown in Fig. 3.

Mechanism of action of nanoparticles in radiation therapy [19]

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2.4 Phototherapy

In phototherapy, heat produced by electromagnetic radiation or light is employed to trigger apoptotic cell death in cancer cells. Additionally, radio-sensitized tumours are likely to respond to radiotherapy much more in the context of thermal stress, improving cancer survival rates [20]. Because they function as photosensitizers, nanoparticles can efficiently transfer light energy from the source to the cancer location. This ultimately results in the production of immunogenic molecules, reactive oxygen species, or antigens that the immune system of the cell recognises and processes to induce the cancer cell to undergo apoptosis [21]. The iron oxide nanoparticle magnetite (Fe3O4) is one of several that may be used as agents to give heat to cancer cells because it may release thermal energy when it comes into contact with a fast-alternating magnetic field. However, gold nanoparticles (AuNPs) can be effectively used for in-vivo phototherapy since they have a substantial absorption around infrared portions of the electromagnetic spectrum and can provide localised heat to kill the region of interest [22]. Process of brain tumour treatment using nanoparticles shown in Fig. 4.

Mechanism of action of nanoparticles in phototherapy in treatment of brain tumor [23]

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2.5 Triggering immunological reactions

The simplest reactions, known as immunological responses, are frequently those that expose the tumour cells to the host immune system so that tumour antigens can kill them [24]. By using biocompatible nanoparticles, the immune system of the patients can be boosted which will result is an effective way to slow the spread of cancer cells. Another approach is to use dual therapeutic compounds (such nucleic acid) packed in nanoparticles to alter the tumour’s immunosuppressive microenvironment and subsequently kill the cancer cells.

2.6 Site-specific cytotoxicity

One reason for utilising drug-loaded nanoparticles aimed for site-specific release is the tailored drug release profile. Nanoparticles can aid in transporting DNA, mRNA, siRNA, and protein within cells. Nano-conjugated biomolecules can deliver targeted cytotoxicity with less side effects compared to systemic drug formulations. Less side effects, superior pharmacokinetics, and a larger EPR impact accompany this increased therapeutic efficacy [25]. Additionally, the high target ligand binding efficiency on the nanoparticle surface influences cancer cell drug disposition and tumour selection.

2.7 Gene therapy for cancer cell growth inhibition

Regulating genes that are actively involved in cellular processes can eliminate cancer cells. Nanoparticles can be engineered to function as agents that trigger specific genes to eliminate cancerous cells. Multiple genes such as STAT3, FGFRL1, HNRNPL, BCL2L1, ATF3, RAB5C, ANG, and others, that have been found to play key role in cellular activities that can influence the growth of tumours and if directed properly may serve to induce antitumor effect. Fe3O4 nano-powder in A549 cell lines can be made to influence cell apoptosis by activating such genes [26].

There are a variety of nanoparticles that have been discovered and have been extensively used in the field of cancer therapy. However, for the sake of this paper, the four broad classes of nanoparticles have been discussed, they are lipid-based, carbon, metallic and polymeric nanoparticles. The utilization of lipid, carbon, metallic, and polymeric nanoparticles in cancer diagnosis and treatment represents a burgeoning area of research, driven by the unique properties and potential advantages these materials offer. This selection is grounded in their biocompatibility, versatility in functionalization, and distinctive physical and chemical properties, which collectively enhance the efficacy and specificity of cancer diagnostics and therapeutics.

3.1 Lipid nanoparticles

Biocompatibility and safety: Lipid nanoparticles (LNPs) are inherently biocompatible due to their composition, which often mimics natural biological membranes. This biocompatibility minimizes the risk of adverse immune reactions and toxicity, making them ideal for clinical applications.

Versatility in drug delivery: LNPs can encapsulate a wide range of therapeutic agents, including chemotherapeutics, nucleic acids (such as siRNA and mRNA), and proteins. This versatility allows for the targeted delivery of these agents to cancer cells, improving therapeutic outcomes while reducing systemic side effects.

Enhanced permeability and retention (EPR) effect: LNPs benefit from the EPR effect, which facilitates their accumulation in tumor tissues due to the leaky vasculature and poor lymphatic drainage of tumours. This property enhances the concentration of therapeutic agents at the tumor site, improving treatment efficacy.

3.2 Carbon nanoparticles

Unique structural and chemical properties: Carbon nanoparticles, including graphene oxide and carbon nanotubes, exhibit unique structural, electrical, and thermal properties that can be exploited for cancer diagnostics and treatment. Their high surface area allows for efficient loading of therapeutic agents and imaging markers.

Photothermal and photodynamic therapy: Carbon nanoparticles can be utilized in photothermal and photodynamic therapy, where they generate heat or reactive oxygen species upon light irradiation. This can selectively destroy cancer cells with minimal damage to surrounding healthy tissues.

Functionalization potential: The surface of carbon nanoparticles can be easily functionalized with targeting ligands, drugs, and imaging agents, enhancing their specificity and multifunctionality in cancer therapy and diagnosis.

3.3 Metallic nanoparticles

Enhanced imaging capabilities: Metallic nanoparticles, such as gold and silver nanoparticles, exhibit strong surface plasmon resonance, which can be harnessed for enhanced imaging techniques like computed tomography (CT), magnetic resonance imaging (MRI), and surface-enhanced Raman scattering (SERS). These properties make them invaluable in the early detection and monitoring of cancer.

Therapeutic applications: Gold nanoparticles, in particular, are used in hyperthermia therapy, where they are heated by external energy sources to selectively destroy cancer cells. Additionally, metallic nanoparticles can serve as carriers for chemotherapeutic drugs, improving their delivery and reducing toxicity.

Multifunctionality: The ease of surface modification of metallic nanoparticles allows for the attachment of various functional groups, targeting ligands, and therapeutic agents, making them highly versatile platforms for simultaneous diagnosis and therapy (theranostics).

3.4 Polymeric nanoparticles

Controlled drug release: Polymeric nanoparticles offer the ability to precisely control the release profiles of encapsulated drugs, enhancing the therapeutic index by maintaining drug concentrations within the therapeutic window for extended periods.

Biodegradability: Many polymers used in nanoparticle synthesis, such as PLGA (poly(lactic-co-glycolic acid)), are biodegradable and approved by regulatory agencies for medical use. This biodegradability ensures that the nanoparticles are safely metabolized and eliminated from the body.

Tailorable properties: The physical and chemical properties of polymeric nanoparticles can be tailored by varying the polymer composition and molecular weight. This flexibility allows for the customization of nanoparticles for specific applications, including targeted drug delivery and responsive drug release in the tumor microenvironment.

This review paper explores these four categories of nanoparticles in depth, ranging from structural properties, characteristic features, advantages and the drawbacks as well that justifies the role of these agents in cancer diagnosis and treatment.

Lipid-based nanoparticles are highly promising and have transformed cancer treatment by enhancing the effectiveness of many medicines against tumours. LBNPs are characterised by their great thermal stability and loading capacity, making them well-suited for use in chemotherapeutic treatments. LBNPs can be derived from natural sources. Hence, they are prepared in large-scale in comparatively easy methods and under low costs. Lipid nanoparticles are associated with chemotherapeutic agents which reduces the dosage and hence toxicity, decreases drug resistance in tumour regions and increases drug levels in tumour tissue by decreasing them in healthy tissue [27, 28]. LBNPs can be classified into 3 groups, namely Liposomes, Solid lipid nanoparticles (SLNs) and Nano Structured Lipid Carriers (NLCs) as shown in Fig. 5.

Traditional versus 3 generations of Lipid NPs [29]

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4.1 Techniques for the preparation of lipid nanoparticles

Lipid nanoparticles can be synthesised using many techniques, including hot and cold high-pressure homogenization, solvent emulsification/evaporation, microemulsion creation technique, and ultrasonic solvent emulsification. The primary method used to produce lipid nanoparticles on a large scale is using the high-pressure homogenization technique.

High-pressure homogenization

SLNs were initially generated using high-pressure homogenization (HPH) as the method. This technique involves the passage of liquid through a thin gap, typically a few micrometres wide, under high pressure ranging from 100 to 2000 bar. This process leads to the dispersion of particles in small and uniform sizes [30]. The HPH approaches have been widely utilised by most industries for diverse purposes [31]. The primary benefit is in the efficient reduction of particle size and minimal contamination, making it suitable for industrial applications, including cost-effective and large-scale production. HPH has two primary temperature classifications, hot and cold, which are determined by the prevailing conditions [32]. SLNs are formed by incorporating the desired material into a lipid mixture through dissolution or dispersion in a melting lipid mixture.

Intense high-pressure homogenization: This method entails elevating the temperature of the lipid phase to 90 °C, and subsequently blending the heated lipid phase with an aqueous phase that contains surfactants at the identical temperature. The pre-emulsion is subjected to homogenization at a temperature of 90 °C using a high-pressure homogenizer for 3 cycles at a pressure of 5 × 107 Pa. Finally, the oil in water emulsion is cooled down to the temperature of the surrounding room in order to transform SLNs or NLCs into a solid state [33].

Cryogenic high-pressure homogenization: This method entails lowering the temperature of the melted lipid phase to trigger the process of solidification, which is then followed by the act of grinding to generate lipid microparticles. The lipid microparticles are evenly distributed in a cold-water phase that contains surfactants, resulting in the formation of a pre-suspension. Subsequently, the pre-suspension undergoes 5 cycles of high-pressure homogenization at room temperature and a pressure of 1.5 × 108 Pa [29].

Technique for the generation of microemulsions: In this process, lipids are heated to the appropriate temperature till they reach their melting point, while the aqueous phase containing surfactants is also heated to the same temperature. Subsequently, the warmed aqueous solution will be added to the melted fats while being stirred constantly at the same temperature. The hot oil in water microemulsion is dispersed in cold water at a ratio of 1 part oil to 50 parts water in order to solidify lipid nanoparticles [35].

The ultrasonic solvent emulsification technique is a process that use ultrasonic waves to generate emulsions. During this process, the lipid phase is dissolved in an organic solvent, such as dichloromethane, and subsequently heated to a temperature of 50 °C. Subsequently, the aqueous phase, comprising surfactants and emulsifiers, is subjected to heating at the identical temperature. Once a part of the dichloromethane has evaporated, the aqueous phase is added to the organic phase while stirring at a temperature of 50 °C. The emulsion undergoes sonication for an appropriate period of time and is subsequently cooled in an ice bath to solidify the lipid nanoparticles.

The solvent evaporation method is used to synthesise lipid nanoparticles. This involves the process of emulsification, followed by the evaporation of the solvent [36]. At first, the liquid is dissolved in an organic solvent that is immiscible with water. Subsequently, the mixture is mixed with water and then undergoes evaporation of the organic solvent under reduced pressure. This process results in the lipid dissolving in the aqueous phase, ultimately leading to the formation of a suspension of lipid nanoparticles in the aqueous phase [37]. The size of lipid particles is contingent upon their concentration. This technique offers multiple benefits, such as its uninterrupted nature, ability to be scaled up, and suitability for use in industrial settings [38]. The disadvantages of this method involve the use of an organic solvent, high temperature, and the difficult control of parameters, all of which affect the dispersion of particles [39].

The membrane contractor is an advanced approach suitable for efficient production of lipid nanoparticles on a large scale. Lipid droplets are created by applying pressure to the lipid phase inside the membrane pore at a temperature higher than the lipid’s melting point, and subsequently isolating the lipid droplets from the aqueous phase. Lipid nanoparticles are formed by the controlled cooling process till they reach the temperature of the surrounding environment. This method provides accurate manipulation of the physicochemical characteristics of the lipid nanoparticles by utilising specified parameters [40, 41].

The supercritical fluid method is a technique that uses a supercritical fluid, often carbon dioxide (CO2), as the solvent for extraction. Under specific circumstances, ethanol or methanol can function as a cosurfactant. Lipid nanoparticles are generated through the extraction process employing carbon dioxide (CO2) at temperatures and pressures that above the critical values of 31 °C and 74 bar, respectively. This method produces lipid nanoparticles in the form of a solid powder or dry particles [42, 43].

Spray-drying is a method employed in various sectors to transform liquid material into a dry powder form. It is a feasible alternative to lyophilization for the manufacturing of solid lipid nanoparticles (SLNs). Lipids with a melting point above 70 °C are suitable. The investigation found that there was a 1% concentration of SLN in a solution that contained either trehalose in water or a mixture of 20% trehalose in ethanol and water [44].

Double-emulsion method: This procedure involves formulating the medicine with a stabiliser to prevent the drug from separating when the solvent evaporates in the outer aqueous phase of water/oil/water emulsion [45].

Film ultrasound dispersion: It involves the rotation and evaporation of the organic solvent in an organic solution that contains lipid and medicine. This process results in the formation of a lipid film [46].

Precipitation method: It is a technique used to separate substances from a solution by causing them to form a solid precipitate. When an organic solvent is combined with an aqueous phase to create a lipid solution, the evaporation of the organic solvent causes the formation of lipid nanoparticles. Subsequent to diffusion and the application of probe sonication, tiny and homogenous solid lipid nanoparticles (SLNs) are formed [47].

4.2 Analysis of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs)

Accurate characterisation of nanocarriers is crucial for their clinical use. Characterising SLNs and NLCs is difficult due to their extremely small size and the dynamic nature of the system, in contrast to other colloidal carriers. The stability and in vivo performance of nanoparticles are directly influenced by the characterization criteria. The SLN and NLC are primarily distinguished by their particle size, shape, polydispersity index (PI), zeta potential, percentage drug entrapment efficiency, drug crystallinity, and stability [48].

Dimensions and form

The accumulation of lipid nanocarriers in the target tissue depends on their physical characteristics, namely their particle size distribution. To ensure the safety, stability, and efficiency of nanocarriers, it is essential to generate homogeneous populations of nanocarriers with a precise size [49]. Laser diffraction (LD) and photon correlation spectroscopy, also known as dynamic light scattering (DLS), are commonly used to determine the size of lipid particles. Both approaches are utilised to assess the distribution of sizes, as represented by the polydispersity index (PI). DLS offers extensive information regarding the homogeneity of a solution and the dimensions of its particles. The ideal particle size for NLCs is below 400 µm. The numerical value of PI ranges from 0.00, which represents a sample with particles of the same size, to 1.00, which represents a sample with particles of different sizes and a high level of polydispersity. PI values below 0.05 are mainly observed when employing highly uniform standards. PI values exceeding 0.7 indicate a significant variation in particle size. Advanced microscopy techniques, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM), may accurately measure particle sizes at scales less than a millimetre and in the nanometer range [50, 51].

Zeta potential

The term “zeta potential” refers to the electric potential difference between a particle’s surface and the surrounding fluid. The term “surface charge” pertains to the magnitude of electrical charge existing on the particles within a water-based dispersion. This parameter is essential in establishing the long-term physical stability of the formulations. The zeta potential of lipid nanoparticles is commonly determined through the assessment of electrophoretic mobility and quantified using photon correlation spectroscopy and LD techniques [50, 51]. In order to achieve excellent physical stability in SLNs and NLCs, it is essential to have a minimum zeta potential of -60.0 mV or higher. For good physical stability, a zeta potential of -30.0 mV or higher is required. Kovacevic et al. [52] discovered that the zeta potential of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) rises in proportion to the amount of oil present. The addition of a surface coating to solid lipid nanoparticles (SLNs) reduces the mobility of the particles when subjected to an electric field, leading to a drop in the zeta potential [53].

Efficiency of entrapment

Drug entrapment efficiency is the ratio of the amount of drug trapped within the carrier to the total amount of drug in the dispersion. The entrapment efficiency is assessed through the utilisation of analytical methods such as UV spectrophotometry or high-performance liquid chromatography (HPLC), together with separation processes like ultrafiltration, centrifugation, and dialysis. These procedures facilitate the quantification of the active component. The assessment of entrapment efficiency is conducted by two main ways, namely direct and indirect methods. The direct approach is directly measuring the quantity of the medicine that is encapsulated, whereas the indirect method requires measuring the amount of medication that is not encapsulated in the supernatant [54]. Usually, the ability of active chemicals to be trapped in lipid nanoparticles is greater than 70%. The entrapment efficiency of an active molecule in lipid carriers is affected by the velocity and duration of agitation, the emulsifier concentration, and the surfactant [54]. The entrapment efficiency is mainly determined by the lipid’s type, concentration, and crystal structure.

Crystallinity of drugs

Differential scanning calorimetry (DSC) is a technique that can be employed to quantify the level of crystallinity in lipid particles. Differential scanning calorimetry (DSC) is an analytical method that uses heat to determine the properties of lipid particles. This approach is characterised by its high speed and accuracy in quantifying the degree of crystallinity in lipids, based on the enthalpy of the lipid. A notable disadvantage of DSC is its inherently destructive character. Powder X-ray diffractometry (PXRD) is a non-destructive method used to evaluate the crystallinity of lipids and examine the crystal structure of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) [55].

In vitro drug release

The drug release profile from solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) is mainly controlled by biodegradation and diffusion processes. The assessment of drug release from these nanocarriers is commonly performed utilising many techniques including side-by-side diffusion cells with a reverse dialysis sac that mimics a biological or artificial membrane, ultra-centrifugation, dialysis bag, centrifugal ultra-filtration, and ultra-filtration. The drug release profile is evaluated using either a UV spectrophotometer or HPLC [56].

Stability

In order to evaluate the stability of SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers), it is possible to analyse the average particle size, size distribution, entrapment efficiency, and drug release profile across different storage periods and temperatures. These analyses should adhere to the guidelines established by the International Council for Harmonisation (ICH). The samples are gathered at precise time intervals and examined for these exact requirements. The drug’s entrapment efficiency and release patterns are evaluated using either a UV spectrophotometer or HPLC [52, 53].

4.3 Liposomes

Liposomes were initially identified and approved for use in 1965, making them the earliest known tiny phospholipid bilayer nanosystems. Spherical vesicles are primarily composed of unilamellar or multilamellar phospholipids [57]. Liposomes often vary in size from 20 nm to over 1 µm. A liposome is usually composed of a hydrophilic center encased by a hydrophobic phospholipid bilayer. This design enables the containment of both water-soluble and water-insoluble medications according on the drug’s pharmacokinetic characteristics.

Hydrophilic medications are contained in the aqueous core, while hydrophobic drugs are enclosed within the lipid bilayer of liposomes. Liposomes can be categorised into two categories based on their size and the number of bilayers they include [58]:1) Unilamellar vesicles and multilamellar vesicles (MLV) are two types. 2) Unilamellar vesicles are categorised into small unilamellar vesicles (SUV) and large unilamellar vesicles (LUV). There are numerous advantages possessed by liposomes which makes them excellent candidate in therapeutic purposes [59]. Liposomes have low toxicity and are biocompatible and biodegradable in nature, which makes them excellent to be used inside living organisms. Structurally liposomes are bilayer which helps protect loaded drugs from enzyme degradation and this also provides for greater degree of flexibility. Moreover, they are non-immunogenous hence avoid unnecessary immunogenous activities inside the organism. However, liposomes have low encapsulation efficacy and short shelf-life which posses as major hindrance to be used as a drug carrier. Liposomes are often adsorped by cells in body and hence fail to reach the targeted tumour region because of intermembrane transfer issues. Also, structurally they are not very stable which has led to search for the next generations of lipid-based nanomaterials as presented in Fig. 6.

Different types of liposomes [60]

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Liposomes are mostly used for co-delivery and controlled release. Combinations of chemical medications, metallic particles, genetic agents, and other chemotherapeutic agents have been developed to treat cancer. A newly devised nanocarrier with liposome encapsulation, entrapping two drugs (irinotecan and floxuridine) demonstrated enhanced effectiveness in treating complex tumours [61]. Cancerous areas typically exhibit an extracellular pH value ranging from 6.8 to 7.0, slightly more acidic than healthy tissue [62]. In such cases the normal release of drug Sorafenib is reduced. However, when cationic liposome (CL) preloaded with sorafenib (Sf) is coated with Carboxymethyl chitosan (CMCS) (a pH-sensitive material), sorafenib release was enhanced. This is called the pH-sensitive property [63]. Liposomes can possess enzyme-responsive, redox-responsive, or light-responsive qualities in addition to their pH-responsive property, based on the tumour microenvironment (TME) and pharmacological attributes [64].

4.4 Solid lipid nanoparticles

Solid lipid nanoparticles were discovered in 1991 by Gasco and Muller. These are spherical in shape and their size range from 50 to 1000 nm. These are first generation of lipid-based nanoparticles and are less expensive. Because of improved structural properties these have long term stability and the drug is released for prolonged time at the correct site and thus SLNs serve as excellent carriers for poorly water-soluble drugs. Moreover, these have gained popularity for therapeutic purposes as they do not cause bio-toxicity of the drug carried and have increased drug-loading efficiency [32,33,34,35, 66,67,68,69]. SLNs can be categorized into 3 classes based on drug loading characteristics: SLN Type I follows a homogenous matrix model, SLN Type II follows a drug-enriched shell model, and SLN Type III follows a drug-enriched core model. However, these particles also come with their own downsides as SLNs have unpredictable gelation formation and have at times reported to cause unnecessary particular growth in cells/ tissues as well as cases of drug expulsion during drug storage. Because of their crystal line structure, they have inherently low incorporation rates into the targeted sites [69]. This may also cause the drug to leak out and get degraded in the body without reaching target site at the capillaries where there is high pressure due to blood flow. Structure of SLNs is shown in Fig. 7.

Structure of SLNs and the way it can be functionalized depending on the selection of drugs, lipids, surfactants and protecting molecules [70]

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SLN can be used to overcome barriers associated with traditional chemotherapy and multidrug resistance in breast cancer treatment like inadequate drug concentrations reaching the tumour, rapid elimination, systemic toxicity and adverse effects. Campos et al., investigated that chitosan-hyaluronic-coated SLNs facilitates the targeting, cellular uptake and the time-/dose-controlled delivery and release of paclitaxel (PAX). These modified systems were stable and also reproducible. Wang et al., formulated resveratrol-loaded SLNs to treat MDA-MB-231 cells. This showed better capabilities to inhibit the proliferation of these cells, than free resveratrol. SLN helps in the development of proteins (transferrin) in (DDS) drug delivery system. Also, commercial antibody conjugated SLN formulations is used for active targeting in breast cancer treatment. Type of SLNs are presented in Fig. 8.

Type of SLNs [71]

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4.5 Nano structured lipid carriers

NLCs are the second iteration of SLN as presented in Fig. 9. These consist of a binary mixture of solid lipid and liquid lipid, forming a hybrid carrier. NLCs consist of mixture of specially blended long chain of solid lipid and short chain of liquid lipid in a ratio 70:30. They have average size between 10 and 500 nm. These were developed to overcome disadvantages of SLNs. NLCs have a greatly improved structure and improved stability because these are the second generation of lipid-based NPs. These have improved loading capacity of drugs and are bio-compatible, non- toxic and non-immunogenous. NLCs can excellently maintain internal structure of proteins and the drugs and other substances they carry. NLCs are of three types: Low Oil, High Oil and Amorphous. However, it is reported that NLC has low loading capacity [72] and it was revealed that drug expulsion occurred during the storage period due to polymorphic transition of the lipid from the nanocarrier matrix.

Structural organisation of different types of NLC: illustrating the different components present in each of the three types of NLC [73]

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Doxorubicin (Dox) a drug used in breast cancer treatment, was found to be more effective in causing cell apoptosis when incorporated with Vitamin D3 loaded Nano structured Lipid Carriers (NLCs) as sown in Fig. 10. In fact, the percentage of apoptosis increase over twofold as compared to using free Dox drug. Given its effects on cell death in comparison to free medicines, fluvastatin may be a viable candidate for prostate cancer therapy when combined with lipoic acid and ellagic acid in a non-lipid combination (NLC) [74].

Structural modifications those can be induced on surface of NLC to use them in different diagnostic and therapeutic purposes for cancer [75]

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A type of nanoscale material having multiple categories based on the element carbon is called a carbon nanomaterial (CNM). Because of their special electrical, thermal, optical, and mechanical qualities, they have found extensive application in a variety of industrial and medical domains. CNMs are thought to be safer and more biocompatible than metal-based nanoparticles in cancer theragnostic applications. Because CNMs are naturally hydrophobic, they combine with chemical medicines through π bonding or hydrophobic bonding. Because of this, CNMs are effective medication delivery systems [76, 77]. Carbon Nano Materials can be classified into 4 categories: graphene, fullerene, carbon nanotube (CNTs) and carbon nano horn (CNHs).

5.1 Graphenes

In 1947, single-layer graphene was theoretically explored by P. R. Wallace. In 1962, Hanns-Peter Boehm and his co-workers experimentally discovered graphene. The term graphene was introduced in 1986 by Boehm et al. Graphene comprises a hybridised carbon sheet with a surface polarity of sp2. It can be divided into single-layer, multi-layer, reduced graphene oxide (rGO), graphene oxide (GO), and multi-layer graphene based on composition, structure, and other characteristics [78]. Graphenes are unusual in their mechanical and electrochemical characteristics as shown in Fig. 11. It is chemically inert, has high density and possess abilities to obstruct molecular entry. It also has higher optical transmittance and high planar surface that allows to load greater amount of drug. Graphene has high hydrophobicity and thermal conductivity of about 5000 W/mK [79,80,81,82]. However, there are certain drawbacks to these nanoparticles as well. Graphene suffers from poor solubility and agglomeration in solution as there exists Van der Waals forces and π bonding which binds the sheets of graphene. This in turn significantly affects toxicity and fabrication of the nanomaterial [83, 84].

Schematic diagram of structure of graphene: showing the typical covalent bonding and sheet like stacking between each layer of graphene [85]

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5.1.1 Synthesis of graphene

a) Top-down methods

Chemical exfoliation

Oxidation–reduction (Hummer’s method): This method involves the oxidation of graphite to graphite-oxide, which is subsequently exfoliated in water to yield graphene oxide (GO). The GO is then reduced to graphene using chemical agents such as hydrazine, sodium borohydride, or through thermal annealing processes [86].

Liquid-phase exfoliation: In this technique, graphite is dispersed in solvents like N-methyl-2-pyrrolidone or dimethylformamide and subjected to sonication, resulting in the formation of graphene nanosheets. Centrifugation is employed to separate the exfoliated layers [87].

Mechanical exfoliation

Micromechanical cleavage: This physical method involves the use of adhesive tape to peel off graphene layers from graphite. Although this method produces high-quality graphene, it lacks scalability [88].

Ball milling: In this approach, graphite is ground in a ball mill with chemical agents, facilitating the production of graphene nanoparticles through shear forces and chemical interactions [89]

Electrochemical Exfoliation

Graphite electrodes undergo electrochemical reactions in an electrolyte solution, leading to the exfoliation of graphene layers. This technique offers control over the thickness and size of the resulting graphene [90].

Laser Ablation

A high-energy laser ablates graphite targets in a solvent, producing graphene nanoparticles. This method is effective for generating small, high-quality graphene sheets [91].

b) Bottom-up methods

1. 1.

   Chemical Vapor Deposition (CVD): Hydrocarbon gases such as methane are decomposed on metal substrates (e.g., copper, nickel) at elevated temperatures, resulting in the deposition of graphene layers. This technique is widely adopted for producing high-quality, large-area graphene [92].

2. 2.

   Pyrolysis: Organic precursors, including glucose and citric acid, undergo thermal decomposition in an inert atmosphere, leading to the formation of graphene nanoparticles. This method allows for precise control over particle size and morphology [93].

3. 3.

   Sol–Gel Process: In this method, graphene oxide is mixed with a gel-forming solution and subsequently reduced to graphene nanoparticles. This technique enables the synthesis of graphene nanoparticles with tailored properties [94].

4. 4.

   Molecular Assembly: Chemical reactions are utilized to assemble small molecular precursors into graphene structures, offering precise control over the chemical composition and structure of the graphene [95].

Additional considerations for synthesise

The efficiency and quality of graphene production in liquid-phase exfoliation are significantly influenced by the choice of solvent. Solvents with surface energies comparable to graphene are optimal [87]. For methods involving graphene oxide, the reduction process is critical. Different reducing agents and conditions—thermal, chemical, or electrochemical—yield graphene with varying degrees of restored conjugated structures [96]. Post-synthesis functionalization, such as with polymers or metals, can tailor the properties of graphene nanoparticles for specific applications, enhancing their utility [97].

5.1.2 Graphenes in Cancer treatment

Graphene has the potential to be used as a medication carrier, however it can be hazardous to human organs by aggregating in tissues and causing oxidative stress. Surface modification of graphene is crucial to address this issue. The Deep Eutectic Solvent (DES) technique is suitable for bonding different functional groups to the surface of graphene. Functionalizing graphene expands its potential uses in sophisticated drug delivery systems. Moreover, the high surface-area-to-volume ratio of graphene is advantageous for drug delivery purposes. Zainal-Abidin et al. detailed the modification of graphene with choline chloride and the combination of DOX. This material exhibited excellent dispersibility and capability for trapping DOX. The functionalized graphene demonstrates enhanced anticancer action by capturing DOX more effectively than virgin graphene [98, 99]. Lucherelli et al. conjugated folic acid to graphene using a PEG chain to achieve targeted administration of DOX. They utilised indocyanine green to monitor the distribution of the compound and anticancer effects within cancer cells. Both in vitro and in vivo research demonstrated decreased toxicity of the multifunctionalized graphene [100]. Research investigated a new technique using an ionic liquid to fluorinate graphene for delivering curcumin. The modified material exhibited increased drug loading efficiency and more potent anticancer properties [101].

5.2 Fullerenes

The C60 structure was developed and modelled in 1970 by R. W. Henson, who was working for the UK Atomic Energy Research Establishment at the time. Sadly, there was not much data to support that new kind of carbon at the time, so the concept was viewed with scepticism and never published. When Sumio Iijima examined an electron microscope image of carbon black in the early 1980s, he was able to identify the C60 molecule because it was forming the core of a particle that had a “bucky onion” structure. Working with James R. Heath, Sean O’Brien, Robert Curl, and Richard Smalley from Rice University, Harold Kroto of the University of Sussex discovered fullerenes in the sooty residue left behind after vaporising carbon in a helium environment in 1985. Discrete peaks, identified as C60 and C70, in the product’s mass spectrum were found to correspond to molecules that contained precisely sixty or seventy carbon atoms or more. The group recognised their organisation as the well-known “buckyballs”. Fullerenes have the shape of a hollow sphere, ellipsoid, or tube. C60, C70, C82, and other typical fullerenes are examples as shown in Fig. 12. Metallofullerenes can be created by incorporating metal atoms such as lanthanides or group III transition elements inside [102]. There are several advantages of Fullerenes as to be used as therapeutic agents. Fullerenes have antimicrobial properties can be improved with the help of inorganic salts. Also, these particles have free radical scavenging ability and can act as antioxidants [103, 104]. Fullerenes also exhibits superior properties in PDT and PTT as they can undergo Type 1, 2, and 3 photochemistry [105]. Importantly, fullerenes can also be utilized as essential components of theragnostic nanoparticles. However, fullerenes have relatively high molecular weight and are quite prone to aggregation due to their hydrophobic nature.

Different types of Fullerene structures ranging from carbon numbers from 24 to 180 [106]

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5.2.1 Synthesis of fullerenes

a) High-temperature methods

Arc discharge method

The arc discharge method, a pioneering technique for synthesising fullerenes, entails creating a strong electric current arc between two graphite electrodes in a non-reactive environment, usually helium or argon. The high temperature generated (about 4000 K) causes the graphite to transform into vapour, resulting in the creation of fullerenes and other carbon nanostructures. The resulting soot, which contains fullerenes such as C60 and C70, is gathered and isolated using organic solvents such as toluene or benzene [107].

Laser ablation

Laser ablation is the process of using a powerful laser to irradiate a graphite target in the presence of an inert gas atmosphere. The laser causes the graphite to turn into vapour, and the subsequent cooling of the carbon vapour results in the creation of fullerenes. This technique facilitates meticulous manipulation of the experimental parameters, hence facilitating the production of diverse fullerene architectures. Nevertheless, it necessitates intricate and costly apparatus [108].

Combustion method

The combustion approach involves the controlled burning of hydrocarbons to generate a soot that contains fullerenes. Usually, an oxygen-rich flame is employed to burn aromatic hydrocarbons, leading to the production of fullerenes along with other secondary substances. The approach described is regarded as being more scalable and cost-effective compared to arc discharge and laser ablation techniques. However, it typically results in inferior purity and a broader distribution of fullerene sizes [109].

b) Low-temperature and chemical methods

Chemical synthesis

The process of synthesising fullerenes comprises the use of carbon-based precursors of smaller size, which undergo a sequence of chemical processes to produce fullerene structures. Despite its intricacy and lower yield, this process is currently impractical for large-scale manufacturing. However, it does enable the synthesis of unique fullerene derivatives with specified functional groups [110].

Template-assisted synthesis

It refers to a method of creating materials or structures by using a template or mould to guide the formation of the desired product. This approach utilises pre-existing templates, such as metal–organic frameworks or zeolites, to direct the production of fullerene structures. Carbon supply undergoes decomposition on the template, leading to the self-assembly of carbon atoms into fullerene molecules. This method has the potential to precisely create fullerene molecules of certain sizes and shapes. However, it is currently at the developmental stage and not commonly employed for large-scale production [111].

c) Plasma-assisted methods

Radio-frequency plasma

RF plasma techniques employ RF energy to induce a plasma state in a gas containing carbon, resulting in the production of fullerenes. This method enables uninterrupted manufacturing and can be adjusted to maximise the output of fullerenes. Nevertheless, it necessitates advanced machinery and meticulous regulation of process variables [112].

Microwave plasma

Microwave plasma refers to a state of matter created by subjecting a gas to microwave radiation, resulting in the ionisation of the gas particles and the formation of a plasma.

Microwave plasma methods utilise microwave radiation to create a plasma in a gas containing carbon precursor. The intense atmosphere in this setting promotes the creation of fullerenes and other carbon nanostructures. This technology has the benefits of scalability and the ability to maintain continuous production. However, it requires the use of intricate equipment and careful control [113].

Extraction and purification

Irrespective of the process used to create it, the final product usually consists of a combination of fullerenes, amorphous carbon, and other secondary substances. Extraction and purification are essential stages, typically requiring the use of organic solvents and chromatographic methods. High-performance liquid chromatography (HPLC) is commonly used to separate and purify different types of fullerene molecules by taking advantage of their varying sizes and solubilities [114].

5.2.2 Fullerenes in cancer treatment

For use in sophisticated drug delivery systems, a variety of fullerene derivatives with enhanced water solubility have been created. Because of their size and amphiphilicity, fullerenes can pass through nearly all biological barriers and entities. It is possible to provide drugs locally with conjugated fullerenes without endangering other body organs. For example, when taken orally, ibuprofen, a commonly prescribed medication for pain and inflammation during cancer therapy, can cause adverse effects such as vomiting, ulcers, gastrointestinal bleeding, and aggravated digestive system. Ibuprofen can be carried by C60 fullerenes with a porphyrin-like transition metal (N4), according to recent density functional theory (DFT) calculations. The drug’s release in the acidic environment of sick cells was verified by quantum investigations [115].

Gemcitabine is an efficacious medication for pancreatic cancer. On the contrary, it does exhibit modest chemoresistivity and insufficient dispersion inside the tumour. Thus, research is currently focused on an alternate route to administer gemcitabine. Gemcitabine and fullerene conjugation is one possible remedy for increased water solubility [116]. The compound’s cytotoxicity can be increased by the oxygen species that blue LED radiation produces in C60 [116]. Seretilamide conjugated with C60 has the ability to penetrate liver cancer cells. When C60-serinol and paclitaxel are combined, the tumour shrinks without causing weight loss as a side effect. Based on computational results, C60 can be successfully loaded with the anticancer agent boronic chalcone and the chemotherapy medication doxorubicin (DOX). Research of the in vivo function of C60-serinol demonstrates that its distribution in the body and excretion from kidney in mice is quick and efficient [117, 118].

5.3 Carbon nano tubes (CNTs)

There are certain controversies in respect to the discovery of CNTs as shown in Fig. 13. However, looking at some obvious information we have come to realize that although Sumio Iijima is cited as the inventor of CNTs (1991), they are believed to be found much earlier. In 1952, L. V. Radushkevich and V. M. Lukyanovich published clear images of 50 nm diameter tubes made of carbon in the ‘Journal of Physical Chemistry Of Russia’. This discovery was largely unnoticed, as the article was published in Russian, and Western scientists’ access to Soviet press was limited during the Cold War period. CNTs are cylindrical tubes formed by sp2 –hybridized carbon atoms and have size ranging from 1 nm to several micrometres. These can be classified into: Single Walled Carbon Nanotubes and Multi Walled Carbon Nanotubes. CNTs can be exploited as therapeutic agents for cancer treatment as these particles can interact with immune cells inside the body and trigger immunological responses [119]. Moreover, CNTs can also boost immunity and suppress tumour growth [120]. CNTs are highly efficient to use as PDT and PTT vehicle. However, there are certain drawbacks that limits the utility of CNT as these are poorly soluble in water and have reported to be toxic at certain cases eliciting persistent inflammation, the development of granulomas, fibrosis, and pathology similar to mesothelioma.

Illustrating the different types of Carbon Nanotubes: SWCNT size varies from 0.5 to 2.5 nm while MWCNT varies in size from 7 to 100 nm [121]

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5.3.1 Synthesis of carbon nanotubes (CNTs) [122]

Chemical vapor deposition method

Chemical Vapour Deposition (CVD) is a method in which gaseous reactants perform a chemical reaction and generate a nanomaterial product that is then placed onto a substrate.

Hydrocarbon gases, including acetylene, ethylene, methane, and others, are used as the precursors for carbon nanotubes [123]. Zeolite, silica, and silicon plates coated with iron particles are often used substrates in the chemical vapour deposition (CVD) process for synthesising carbon nanotubes (CNTs). Iron, cobalt, nickel, molybdenum, and iron-molybdenum alloys are used as metal catalyst nanoparticles in the manufacturing of single-walled carbon nanotubes.

Synthesis of CNTs by thermal CVD method

Carbon nanotubes (CNTs) are synthesised using the thermal chemical vapour deposition (CVD) method, where hydrocarbon gas is used as the carbon source. This method entails the insertion of a quartz tube into a furnace that is maintained at a high temperature (500–900 °C) and heated using an RF heater. The catalyst-coated substrate is inserted into a crucible and subsequently placed within a quartz tube that is filled with an inert gas, such as argon. The hydrocarbon gas, serving as a carbon source, is introduced into the quartz tube and undergoes a pyrolysis reaction, leading to the creation of gaseous carbon atoms. The carbon atoms on the substrate create multi-walled carbon nanotubes (MWCNTs) by adhering to the substrate and connecting with each other through Vanderwaal forces of attraction [124]. Fe, Co, and Ni catalyst nanoparticles are used to produce single-walled carbon nanotubes.

Synthesis of CNTs by electric arc discharge method

This method entails the application of a voltage ranging from 20 to 25 V across the electrodes made of pure graphite, which are positioned 1 mm apart. The electrodes are positioned within a quartz enclosure that is filled with helium gas at a pressure of 500 torr. When the electrodes come into contact with each other in these conditions, it produces an electric arc. The energy produced in the arc is transferred to the anode, leading to the ionisation of the carbon atoms in the pure graphite anode. This process leads to the generation of C + ions and the production of plasma, which denotes atoms or molecules in a gaseous state at elevated temperatures. The positively charged carbon ions travel towards the cathode, where they undergo reduction, get deposited, and subsequently grow into carbon nanotubes (CNTs) on the cathode. As the size of carbon nanotubes (CNTs) increases, the length of the anode decreases. Nevertheless, the electrodes are consistently modified to provide a constant 1 mm gap between them. Proper cooling of the electrodes helps ensure the uniform deposition of carbon nanotubes (CNTs) on the cathode [125]. This can be achieved by ensuring that an inert gas is kept at the suitable pressure. This method entails the production of multi-walled carbon nanotubes by incorporating catalyst nanoparticles of Fe, Co, and Ni into the central section of the positive electrode to create single-walled carbon nanotubes.

Physical vapor deposition (PVD) method

Physical Vapour Deposition (PVD) is a technique that involves converting a chemical into a gaseous state and then depositing it onto the surface of a substrate. The main carbon source used is solid graphite, which is exposed to laser irradiation, causing the carbon atoms to evaporate and become gaseous. The laser source utilised for transforming the target material into vapour atoms can be either a continuous laser source, like a CO2 laser, or a pulsed laser source, such as a Nd:YAG laser (Neodymium doped Yttrium Aluminium Garnet, Nd:Y3Al5O12). The substrate used in this method is a copper collector that is cooled by water. The carbon atoms in vapour form are placed onto the substrate and then grow into carbon nanotubes (CNTs). Argon gas is commonly used as an inert gas that flows continuously towards the water-cooled copper collector at a steady rate.

Synthesis of CNTs by laser ablation method

Laser ablation is a type of physical vapour deposition (PVD) technique in which a laser is employed to vaporise a graphite target. The procedure entails positioning the graphite target at the centre of a quartz chamber, which is then filled with argon gas and maintained at a temperature of 1200 °C. The graphite target is vaporised using either a continuous laser source or a pulsed laser source. The argon gas flow directs the gaseous carbon atoms generated from the target towards a copper collector that is kept at a low temperature. The carbon atoms are deposited and grown as carbon nanotubes (CNTs) on a chilled copper collector. When a laser beam is continuous, it causes the carbon atoms to undergo uninterrupted vaporisation. Using a pulsed laser beam allows for the precise measurement of carbon nanotube (CNT) formation, as each pulse of the laser beam precisely corresponds to the quantity of carbon atoms that are vaporised [126]. This method entails the production of multi-walled carbon nanotubes by the use of catalyst nanoparticles composed of iron (Fe), cobalt (Co), and nickel (Ni) for the synthesis of single-walled carbon nanotubes. The acquired CNTs undergo purification to obtain them in their most refined state.

Pulsed laser deposition method

Pulsed Laser Deposition (PLD) is a method for depositing thin films. It involves using a pulsed laser beam to vaporise the target material, causing the vaporised atoms to deposit onto substrates. The furnace is equipped with a target located at the bottom and a substrate fixed on the top. The Nd:YAG laser emits a pulsed beam that is directed towards the target, causing the target atoms to vaporise and form a high-temperature plume [127]. The plume migrates towards the substrate where it is deposited and undergoes growth as carbon nanotubes (CNTs). The quantity of material ablated is exactly proportional to each laser beam, allowing for precise control and calibration of the deposition rate.

5.3.2 CNTs in cancer treatment

In biological settings, CNTs, which are hydrophobic materials, show nonuniform dispersity. The CNT surface can be functionalized to get around this restriction. CNTs produce carboxylated surfaces when they come into contact with oxidative substances. Drugs can be put into the evenly dispersed, biocompatible carboxylated carbon nanotube (CNT) materials. [128]. A functionalized MWCNT that targets cancer and penetrates cells has been reported [129]. The results using the substance suggested increased permeability of the blood–brain barrier, enhanced antitumor efficacy against glioma tumours, and increased ROS levels supporting anticancer activity. The compound’s selectivity for glioma cells and its ability to penetrate the blood–brain barrier were linked to its anticancer properties [129]. In addition to being more harmful to healthy tissues, the accumulation of carbon nanotubes (CNTs) makes it difficult to estimate the cytotoxicity of an anticancer delivery system. Pennetta et al. functionalized SWCNTs and MWCNTs with pyrrole polypropylene glycol (PPGP) both covalently (CNT/PPGPc) and noncovalently (CNT/PPGPs) then conjugated these materials with DOX to aid in the uniform dispersibility and biocompatibility of CNTs. At a lower dose of DOX, the novel CNT/PPGP/DOX systems were linked to cell death in lung cancer and melanoma. Additionally, the homogenous distribution of CNT, PPGP, and DOX made it simpler to assess cytotoxicity [130].

5.4 Carbon nano horns (CNHs)

Single-walled carbon nano horns (SWNH or SWCNH) is the name given by Sumio Iijima and colleagues in 1999 to horn-shaped sheath aggregate of graphene sheets. Very similar structures had been observed in 1994 by Peter J.F. Harris, Edman Tsang, John Claridge and Malcolm Green. CNHs have conical structure and the diameter ranges between 2 and 5 nm, and total size is around 100 nm. CNHs have complex structure comprising of larger spherical superstructures forming with sp2 hybridized carbon atoms [131]. CNHs have excellent drug-loading capacity and photothermal abilities which makes it a suitable candidate for therapeutic purposes. However, solubility of CNHs is low which may cause hindrance to its use as drug carrier agent and hence it requires surface modification to serve as justified nanocarriers in human tissue. Representation of Carbon Nanohorn as drug delivering agent for cancer treatment is shown in Fig. 14.

Carbon nanohorn as drug delivering agent for cancer treatment [132]

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5.4.1 CNHs in cancer treatment

CNHs can be utilised in therapeutic applications where CNHs can be functionalized with targeting ligands such as antibodies, peptides, or small molecules to achieve targeted delivery to cancer cells. This approach minimizes off-target effects and enhances the therapeutic index of anticancer agents. CNHs can be used as carriers for gene therapy, delivering therapeutic genes or small interfering RNA (siRNA) to cancer cells. This approach can silence oncogenes or restore the function of tumor suppressor genes, providing a genetic basis for cancer treatment. CNHs can also be engineered for multimodal therapy, combining drug delivery, photothermal therapy, and photodynamic therapy. This synergistic approach can improve treatment efficacy and overcome the limitations of single-modality therapies. For imaging purposes, CNHs can be functionalized with imaging agents for diagnostic purposes. Their strong NIR absorbance and fluorescence properties make them suitable for use in techniques such as NIR fluorescence imaging and photoacoustic imaging, facilitating early tumor detection and real-time monitoring of therapeutic responses. Nanohorns possess drug-loading and photothermal capabilities, rendering them appropriate for fabricating Drug Delivery Systems (DDS) with these dual attributes. Yang et al. created a device utilising single-walled carbon nanohorns that are loaded with two chemotherapeutic medicines. Single-walled carbon nano horns (SWNHs) underwent modification by the utilisation of poly and mPEG-PLA, employing hydrophobic-hydrophobic and π–π stacking interactions. Cisplatin and DOX were individually placed onto modified nanohorns. The nanocarrier exhibited high loading efficiency and demonstrated both photothermal characteristics and pH-responsive release capability. According to the article [133], both the original breast cancers and the later lung tumours were completely eliminated. Carbon nanohorns (CNHs) can be functionalized with specific ligands to enable their application in targeted chemical therapy. A carbon nanohorn (CNH) loaded with cisplatin and conjugated with a monoclonal antibody (mAb) D2B, which specifically targets prostate-specific membrane antigen (PSMA) on prostate cancer cells, showed enhanced effectiveness and selectivity in eliminating PSMA-positive prostate cancer cells compared to hybrid antibody-CNHs and cisplatin-CNHs [134].

Metallic nanoparticles are metal nanoparticles with at least one dimension between 1 and 100 nm. Metallic nanoparticles (0D), metallic nanowires and rods (1D), metallic sheets and platelets (2D), and metallic nanostructures (3D) are the four primary categories into which we can divide metallic nanomaterials. There are other ways to manufacture and stabilise metallic nanoparticles; however, the chemical procedure, steric stabilisation, and static stabilisation are the three most often used and well-liked approaches. Using the proper reduction agents, metallic ions are reduced in a solution through a chemical process. The most popular technique for creating nanoparticles is this one. When there is static stabilisation, the metallic nanoparticles are stabilised by an electrical double layer that forms from the absorption of negatively charged ions. By repelling individual nanoparticles from one another, this charged layer can stop further agglomeration. “Zeta potential” is a parameter used to quantify the strength of this electrical double layer. Only polar liquids that can dissolve electrolytes, such as water and ethanol, can be used with this technique. In the third technique, known as steric stabilisation, the metallic nanoparticles are capped with a substance such as a polymer, surfactant, or ligand, usually one that has long alkyl chains attached to the particle surface. These organic molecules’ long, extended chains prevent the individual particles from aggregating by pushing aside any that are getting too close to one another.

Scientists have developed metal nanoparticles with almost all stable metals in the periodic table. However, the most extensively explored metallic nanoparticles are gold and silver. There have been several preclinical and clinical trials exploiting these nanoparticles. Besides the silver and gold nanoparticle, some other metallic nanoparticles include iron-based nanoparticles and copper nanoparticles. In general, metallic NPs can be used for following purposes such as in early detection of tumour/ cancerous cells, in drug delivery system (both Active & Passive), in enhancing the efficiency of drug functioning and in post-surgery patient care and management. Shapes based classification of Metallic NPs shown in Fig. 15.

Classification of metallic NPs based on shapes [135]

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6.1 Gold nanoparticle (AuNPs)

Gold nanoparticles are tiny particles of gold with dimensions typically ranging from 10 to 20 nm. Gold nanoparticles exhibit significant light absorption with a peak at approximately 520 nm in water-based systems. They are commonly produced and stored as a suspension in a watery solution called a colloidal suspension. A gold colloidal suspension containing spherical particles in water has a vibrant red hue. The color is a result of localized surface plasmonic resonance (SPR). The reason that AuNPs find such extensive application in therapeutical approaches for cancer treatment is that it has several remarkable properties such as tunability which allows us to modify it into any desirable shape as per the need of drug delivery or detection purpose. It is highly biocompatible in nature and compatible with body cells, organelles and tissues. It also allows for surface functionalization and thus enable attach with several bio-agents like antibodies, genes, ligand to be used for therapeutic purposes. Being metallic in nature, it also has excellent optical properties and tend to show fluorescence. However, gold nanoparticles are more expensive than most other nanomaterial which limits its utility at many cases. And it has been reported at few cases that properties of gold nanoparticles such as shape, size, surface chemistry, targeting ligand, elasticity, and composition has caused certain toxic effect on the internal cells due to which reticuloendothelial cells get affected in their presence of AuNPs.

6.1.1 Synthesis of gold nanoparticles [136,137,138,139]

I. Physical methods

Physical methods utilize physical processes to produce gold nanoparticles.

a) Evaporation–Condensation: This method involves heating a gold source until it evaporates, followed by condensation of the vapor to form nanoparticles. The primary advantage is the production of pure nanoparticles, but it requires high energy input and specialized equipment.

b) Laser Ablation: A high-power laser ablates a gold target submerged in a liquid to produce nanoparticles. This method allows for precise control over particle size and shape but is expensive and requires sophisticated equipment.

II. Chemical methods

Chemical methods are the most common techniques for synthesizing gold nanoparticles due to their versatility and efficiency.

a) Chemical Reduction: Gold ions are reduced to gold nanoparticles using reducing agents such as sodium citrate, ascorbic acid, or sodium borohydride. This method is simple, cost-effective, and allows control over particle size. However, potential contaminants from reducing agents can be a drawback.

b) Turkevich Method: A well-known chemical reduction method where sodium citrate is used to reduce gold (III) chloride in boiling water, producing spherical nanoparticles. This method is straightforward and widely used, but primarily yields spherical particles.

c) Brust-Schiffrin Method: Involves the reduction of gold ions in a two-phase liquid system using thiol compounds, allowing for the synthesis of small, monodisperse nanoparticles. This method provides good control over particle size but involves the use of organic solvents and thiol ligands.

d) Seed-Mediated Growth: Small gold seed nanoparticles are first synthesized and then grown to larger sizes using additional gold precursor and reducing agent. This method allows precise control over particle size and shape but can be complex and time-consuming.

e) Microemulsion: Nanoparticles are synthesized within microemulsions, which are mixtures of oil, water, and surfactant. This technique offers control over particle size and shape but may involve surfactants that are difficult to remove, affecting purity.

III. Biological methods

Biological synthesis methods leverage biological organisms or biomolecules for the eco-friendly production of gold nanoparticles.

a) Plant Extracts: Plant extracts containing natural reducing agents can convert gold ions into nanoparticles. This method is eco-friendly, cost-effective, and simple, though variability in plant extract composition can affect reproducibility.

b) Microbial Synthesis: Bacteria, fungi, or algae are used to reduce gold ions to nanoparticles. This approach is sustainable and environmentally friendly, but it is generally slower than chemical methods and can introduce biological contaminants.

IV. Hybrid methods

Hybrid methods combine different techniques to enhance the synthesis process and nanoparticle quality.

a) Sonochemical Method: Ultrasonic waves are used to enhance chemical reactions during nanoparticle synthesis, producing nanoparticles quickly and uniformly. However, it requires specialized ultrasonic equipment.

b) Photochemical Method: Light, often UV, is used to drive the reduction of gold ions to nanoparticles. This method can be conducted at room temperature and offers control over nanoparticle properties but necessitates a light source and photoreactive agents.

c) Electrochemical Methods: These methods employ electrochemical cells to synthesize gold nanoparticles. Gold ions are reduced at the cathode of an electrochemical cell to form nanoparticles. This method allows for precise control over synthesis conditions but requires an electrochemical setup and often involves solvents and electrolytes that need careful handling.

6.1.2 Application of gold nano particles

Drug carrier

Gold nanoparticles are utilised as drug carriers due to their surface plasmon resonance (SPR), optical characteristics, and adjustable features. They can be manufactured in a wide variety of core diameters, from 1 to 150 nm, which facilitates controlling their dispersion. Gold nanoparticles are easily changeable because to the negative charge on their surface, allowing for easy functionalization with biomolecules such as medicines, targeting ligands, and genes. AuNPs are biocompatible and non-toxic, making them ideal for use as medication carriers. Scenario: Methotrexate (MTX) has been utilised in cancer treatment for many years. Conjugating MTX with gold nanoparticles resulted in faster and higher accumulation of MTX in tumour cells, leading to increased cytotoxicity against several tumour cell lines compared to free MTX [140,141,142].

Photothermal therapy

Gold nanoparticles are utilised in Photothermal Therapy (PTT) and Photodynamic Therapy (PDT) for cancer treatment. Example: For PTT/PDT dual therapy, Seo et al. used gold nanorods coated with mesoporous silica and loaded with methylene blue. The silica shell’s pores physically absorbed the photosensitizer. For cells transfected with gold nanorods, the viability of CT-26 cells (murine colon cancer) dropped by 31% when exposed to near infrared (NIR) light at 780 nm and dropped by 11% for cells loaded with methylene blue (MB) nanocomposites, demonstrating a synergistic effect of dual therapy [143].

Photoimaging

An innovative technology that aids in the early detection of tumours and assists surgeons in providing precise therapy. Surgeons had a significant barrier in accurately distinguishing between the boundaries of the tumour and the surrounding healthy tissue. Magnetic Resonance Imaging (MRIs) and Computed Tomography (CT) scans may only detect cancers once they exceed a particular size threshold of several millimetres or around 10 million cells. Nevertheless, AuNPs simplify the process. Millions of modified gold nanoparticles are injected directly into the tumour, where they attach precisely to the cancer cells and emit light, aiding surgeons in distinguishing between the tumour and healthy cells. Gold nanoparticles, such as nanorods, nanocages, and nano shells, are biologically harmless and offer enhanced spatial and temporal resolution for imaging cancer cells, making them the top choice for cancer therapy optical imaging. [141, 143]. Role of gold nanoparticle in various fields of cancer detection and treatment is shown in Fig. 16.

Role of gold nanoparticle in various fields of cancer detection and treatment [144]

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6.2 Silver nanoparticle (AgNPs)

One of the most widely used nanomaterials worldwide is silver nanoparticles. Colloidal solutions containing spherical silver nanoparticles exhibit a vivid yellow colour and generally peak at 420 nm in terms of absorbance. The most popular method for making these is to use a reducing agent to reduce silver salt to a zerovalent state. Due to their distinct optical, electrical, and thermal characteristics, they are widely used in many different fields. Silver nanoparticles are superior to other therapeutic agents when utilised as cancer therapy agents because of a number of significant features. AgNPs have extraordinary optical features; the oscillating electromagnetic field leads the free electrons in silver to collectively oscillate coherently at a certain wavelength of light. As a result, there is a charge separation with regard to the ionic lattice, which causes a dipole oscillation to occur parallel to the direction of the light’s electric field. The oscillation’s maximum amplitude occurs at a particular frequency known as surface plasmon resonance (SPR). By adjusting the particle size, shape, and refractive index close to the particle surface, one can modify the absorption and scattering characteristics. AgNPs are also anti-inflammatory in nature causing apoptosis of inflammatory cells and altering cytokinesis process involved in healing of wounds. Other than these, the antibacterial and fungicidal effects of silver are already known which has enabled them to be used in so many other therapeutical approaches. Silver particles are highly toxic to microorganisms because Ag + ions cause a greater degree of structural and morphological changes leading to cell death, and are also effective and fast-acting fungicide killing a broad range of fungus. There are still some limitations on the extensive utility of the silver nanoparticles as there are certain manufacturing issues associated with AgNPs and they exhibit limited carrying capacity. It has also been seen that AgNPs are removed by physiological barriers and are often barred from reaching the targeted tumour because of Enhanced Permeation and Retention effect (EPR).

6.2.1 Synthesise of silver nanoparticles [137, 145, 146]

I. Physical methods

A) Evaporation–Condensation: This method involves heating a silver source until it evaporates, followed by the condensation of the vapor to form nanoparticles. The primary advantage of this method is the production of pure nanoparticles. However, it requires high energy input and specialized equipment, making it less accessible for routine applications.

b) Laser Ablation: In this technique, a high-power laser ablates a silver target submerged in a liquid, producing nanoparticles. This method allows for precise control over particle size and shape. Nonetheless, it is expensive and necessitates sophisticated equipment, limiting its widespread use.

II. Chemical methods

Chemical reduction is the most common method, involving the reduction of silver salts (e.g., silver nitrate) in the presence of reducing agents like sodium borohydride or hydrazine. This method allows for precise control over nanoparticle size and shape but may involve toxic chemicals. Silver ions are reduced to silver nanoparticles using reducing agents such as sodium borohydride, citrate, or ascorbate. This method is simple, cost-effective, and allows for control over particle size. However, the presence of residual contaminants from the reducing agents can be a disadvantage.

III. Biological methods

These green synthesis methods use biological entities such as plant extracts, bacteria, fungi, and algae as reducing and stabilizing agents. Biological methods are environmentally friendly and can produce biocompatible AgNPs with potential therapeutic applications.

6.2.2 Application of silver nano particle

Wound dressing and antimicrobial actions

AgNPs’ properties have been studied for use in wound dressing applications in TERM (tissue engineering and regenerative medicine). Burns and other types of chronic wounds are particularly vulnerable to microbial infection. Furthermore, the rising prevalence of infections linked to bacteria resistant to drugs is a difficult health issue that necessitates the inclusion of antimicrobial elements in scaffold designs in order to promote wound healing. Scaffolds composed of poly (vinyl alcohol) (PVA), poly (vinyl chloride) (PCL), gelatin, chitosan-alginate, and cellulose acetate have all included these particles. Every scaffold that was produced had potent antibacterial action.

Therapeutical treatment

Photothermal Therapy: AgNPs can be used in photothermal therapy, where they convert light energy into heat upon irradiation with near-infrared light. The localized heating effect can induce tumor cell death with minimal damage to surrounding healthy tissue.

Radiotherapy Enhancement: AgNPs induce cytotoxic effects in cancer cells by generating reactive oxygen species (ROS), leading to oxidative stress, mitochondrial damage, and apoptosis. This selective cytotoxicity towards cancer cells spares normal cells to a greater extent. AgNPs can also interact with cellular DNA, causing strand breaks and inhibiting replication. This leads to cell cycle arrest and apoptosis in cancer cells. Hence, AgNPs can act as radiosensitizers, enhancing the effects of radiotherapy by increasing the generation of ROS and DNA damage in cancer cells when exposed to ionizing radiation.

Colloidal macromolecules with sizes ranging from 10 to 1000 nm are known as polymeric nanoparticles. In the early stages, nanoparticles were created using polymers such polymethyl methacrylate (PMMA), poly-acrylamide, polystyrene, and polyacrylates [147, 148]. Nevertheless, the drawback of these materials was their non-biodegradable polymer, which led to reports of persistent inflammation, biotoxicity, and the accumulation of these polymeric nanoparticles. Consequently, natural polymers such as polylactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA), poly (amino acids) [9], and poly(ε-caprolactone) (PCL) were gradually incorporated. These natural polymers include chitosan, alginate, gelatin, and albumin. These polymers are excellent in addition to being biocompatible and biodegradable. First off, PNPs have a high surface-to-volume ratio, which facilitates surface binding of a variety of agents. PNPs have the ability to transport many substances, including radionuclides, small interfering RNAs (siRNA), and anti-cancer medications, to specific locations. Studies have also shown that the surface coating of PNPs facilitates their interaction with the membranes of the blood–brain barrier (BBB) endothelial cells, which in turn allows for endocytosis. This ultimately allows the drugs that the PNPs enclose to reach their target without being impeded by the body’s natural barriers. PNPs are important components that have been utilised in the theragnostic for cancer, which combines diagnostic and treatment simultaneously. In recent years, fluorescent polymeric nanoparticles (FNPs) have been recognised as innovative theragnostic materials. Additionally, ultrasound-sensitive PNPs have become a useful tool for the detection and management of cancer. But like every other group of nanoparticles, polymeric nanoparticles come with their own sets of drawbacks and limitations such as these particles undergo toxic degradation and toxic monomers aggregation, and in terms of future perspective we do need to study their chemical properties vigorously such that we can design and fabricate the particles in way we can address these downturns [149].

7.1 Synthesis methods of polymeric nanomaterials [150,151,152,153,154]

a) Emulsion polymerization: Emulsion polymerization is a widely used method for synthesizing polymer nanoparticles. An emulsion consisting of monomer, water, and surfactant is prepared, followed by the addition of a water-soluble initiator to start the polymerization. The reaction occurs in the micelles formed by the surfactant, resulting in the formation of polymer nanoparticles. The advantage of this method is that it produces high molecular weight polymers exhibiting high reaction rates and yields, also allows control over particle size by adjusting surfactant concentration. However, some of the drawbacks of the method include: it tquires surfactants, which may need to be removed post-synthesis and can cause potential residual monomer and surfactant contamination.

b) Miniemulsion polymerization: Miniemulsion polymerization involves forming stable nanodroplets through high-energy input, which then undergo polymerization. A mixture of monomer, water, surfactant, and high-energy input (ultrasonication or high-shear mixing) forms stable nanodroplets. An initiator is added to these nanodroplets to induce polymerization, resulting in polymer nanoparticles. This process produces smaller particle sizes and narrower size distribution compared to emulsion polymerization. It allows better control over particle morphology. Limitations of this process includes requirement for high-energy input and stabilization of miniemulsions can be challenging.

c) Dispersion polymerization: Dispersion polymerization enables the formation of polymer nanoparticles in a single step. A monomer is dissolved in a solvent along with a stabilizer and an initiator. Polymerization starts in the continuous phase, and the growing polymer chains precipitate out to form nanoparticles. The stabilizer prevents agglomeration and controls particle size. It is a simple, one-step process with easy recovery of polymer nanoparticles, providing good control over particle size. However, it is limited to monomers that are soluble in the reaction medium and requires careful selection of stabilizers.

d) Nanoprecipitation: Nanoprecipitation is a straightforward method for producing polymer nanoparticles without the need for surfactants or stabilizers. A polymer or monomer solution in a good solvent is rapidly mixed with a nonsolvent (e.g., water). Rapid diffusion of the solvent into the nonsolvent leads to the formation of polymer nanoparticles. It is a simple and rapid process. and does not need for surfactants or stabilizers. The downside of this process is that it is limited to hydrophobic polymers and can cause potential broad particle size distribution.

e) Self-assembly: Self-assembly is a versatile method for creating various nanostructures from amphiphilic block copolymers. Amphiphilic block copolymers self-assemble in a selective solvent to form micelles, vesicles, or other nanostructures. The self-assembled structures are stabilized by the selective solvent and intrinsic interactions between polymer blocks. It is a versatile method for creating a variety of nanostructures. Also, it can encapsulate both hydrophilic and hydrophobic drugs. Some of the limitations are: it requires precise control over polymer block composition and conditions and can cause structural instability in different environments. There are three broadly classified areas under the polymeric nanoparticles which is important to look into with respect to cancer diagnosis and treatment. They are micelles and dendrimers.

7.2 Micelles

These are a group of polymeric nanoparticles extensively studied and researched in areas concentrating in the field of delivery of anticancer drugs the recent time. Varying from the size range of 10–100 of nanometres, polymeric micelles structurally have two significant parts: hydrophobic core and hydrophilic shell. While the hydrophobic core is efficient in binding to various hydrophobic drugs, such as cisplatin, doxorubicin, camptothecin, paclitaxel, and so on [155, 156], the hydrophilic shell made of polyethylene glycol (PEG) help stabilizing the structure, also the advantage of using PEG is that these particles are not recognized and eliminated by the reticuloendothelial system. Hence structurally considered, micelles are potentially effective in enhancing the time for the drugs to stay in bloodstream and thus reach the target without getting absorbed or eliminated at any other sites. Micelles are utilised for medication delivery to enhance the bioavailability and anti-cancer efficacy of chemotherapeutic chemicals, DNA, and siRNA and simultaneously, reduce toxicity and side effects otherwise caused when carried without the aid of the nanoparticles [157]. It also possible to chemically alter the surface structure of the micelles by introducing peptides, protein, sugar, nucleic acid ligands (e.g., aptamer), antibodies, small organic molecules as well as other tumour-targeting agents to target tumour proactively [158,159,160].

7.3 Dendrimers

The Greek words “Dendron” and “meros,” which are translated as “tree” and “parts,” are combined to form the word “dendrimer,” which explains their branched nature [161]. Flory first proposed the concept of branching molecules in 1941, but there was not yet sufficient experimental evidence to justify it. Vögtle and colleagues released the first study on dendritic structure in 1978. They used divergent synthesis to produce a dendritic structure. Later, in 1981, 1983, and 1985 Denkewalter et al., Tomalia et al., and Newkome et al. confirmed this finding. Hawker and Frechet pioneered the convergent approach in 1990. Dendrimers are artificial polymers that possess a variety of unique traits, unlike traditional polymers. The particles typically range in size from 1 to 10 nm, with particularly designed big dendrimers reaching sizes of 14–15 nm. Dendrimers are characterised by their highly branching structure and easily adjustable surfaces. Dendrimers consist of three main structural components: a central core that encapsulates theragnostic agents through noncovalent bonding, branches that provide the internal dendritic structure, and an outer surface attached with functional surface groups [162]. All branching monomers stem from a single core and can be categorised into two categories based on their growth directions: divergent growth and convergent growth. Dendrimers possess several exposed anionic, neutral, or cationic terminal groups on their surface, influencing the interaction with hydrophilic or hydrophobic substances [163]. The objects are radially symmetric, spherical, uniform in size, and consistent in composition [164]. Studies have revealed that dendrimers are used in extensively in nanomedicine [165, 166] because of their size as well as that some dendrimers have their own therapeutic benefits, owing to their antifungal, antibacterial, and cytotoxic qualities [167, 168]. And when looked as cancer therapeutic agent, dendrimers are potential agent for carrying the anticancer drugsDendrimers also possess characteristics such as low viscosity, high solubility, mixability, and strong reactivity. Various dendrimers have been created for cancer treatment, including polyamidoamine (PAMAM), PPI (polypropylenimine), PEG (poly (ethylene glycol)), Bis-MPA (2,2-bis(hydroxymethyl) propionic acid), 5-ALA (5-aminolevulinic acid), and TEA (triethanolamine) [169]. Dendrimers can deliver the medicine in two ways in cancer therapy. Drug molecules can be trapped within the dendritic structure or chemically linked to the surface or other components of dendrimers to create polymer-drug conjugates.

Nanotechnology holds the key to revolutionize the cancer detection, diagnosis and therapy with the use of nanoparticles. In comparison to the normal particles, NPs posses better structural stability and composition, unique properties like biocompatibility, non-toxicity, immunogenicity and so on to be exploited as agents in oncogenic treatment. The ease of their application, the precision of their reaching the targeted tumour area, their effectiveness of prolonging the drug disposal in the right area, in spite of being super microscopic and not harming or affecting the surrounding healthy cells are actually the activities nanoparticles are doing if told in a simple way. In achieving effective and precise DD in combination with general therapeutics and overcoming MDR by the justified use of surface functionalizing agents, nanoparticles are achieving miracle and constantly easing out from the difficulties of the traditional and conventional methods of treatment and therapeutics. Several research has already been done to highlight and do justice to the fact that nanoparticles are potential enough to guide us to finding permanent solution to this deadly disease but the need of the hour is that we bring the NPs for clinical trials. Every year the number of studies and experiments to revolutionize the application of nanoparticles in cancer treatment is praiseworthy but still in the area of trials there hasn’t been a lot effort given. We are still far from actually putting NPs into practice, and till date not many NP based drugs are released for clinical use and trial. Moreover, there are several important factors we need to work upon like enhancing targeting specificity, drug capacity, efficacy, bio-availability and reducing the toxicity of nanomaterials loaded drugs toward normal cells. It is essential to test nanomaterials in models that resemble more in vivo environment and therefore we can slowly achieve the dream of producing NP based drugs to be used on population more often.

In this article we mainly focus on the 4 broad group of NPs namely lipid-based NPs, carbon NPs metallic NPs and Polymeric NPs as well as their characteristics and the different work that has been done exploiting these nanoparticles for cancer treatment and diagnosis. The reason for choosing these four groups is that these are the broad groups of NPs with wide range of properties and characteristics those are actually advantageous to be used in practical application for cancer treatment. Under the subcategories of the nanoparticles, we can find range of application from diagnosis, treatment to therapeutics; some with their unique properties of influencing the immunogenous response of the body while some directly interacting with the tumour region.

We anticipate that the progress in nanobiotechnology and cancer therapy will lead to a significant advancement in clinical translation for cancer treatment. This will result in the introduction of additional nanomaterial-based medications to benefit cancer patients globally.