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CN111701032A - 兼具药物控释及成像功能的介孔氧化硅复合体的制备方法 - Google Patents

兼具药物控释及成像功能的介孔氧化硅复合体的制备方法 Download PDF

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CN111701032A
CN111701032A CN202010584377.1A CN202010584377A CN111701032A CN 111701032 A CN111701032 A CN 111701032A CN 202010584377 A CN202010584377 A CN 202010584377A CN 111701032 A CN111701032 A CN 111701032A
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nanoparticles
msio
solution
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peg
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房慧颖
蒋伟
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Chongqing University Cancer Hospital
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Chongqing University Cancer Hospital
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Abstract

本发明公开了一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，如下步骤：(1)Au/Fe3O4@mSiO2‑SH分子探针的制备；首先，制备Au纳米颗粒；其次，制备Au/Fe3O4壳核结构纳米颗粒；然后，应用反相微乳液法制备Au/Fe3O4@mSiO2‑SH纳米颗粒；(2)Au/Fe3O4@mSiO2/DOX‑SS‑PEG‑HA的制备；DOX乙醇溶液中加入Au/Fe3O4@mSiO2‑SH纳米颗粒，所得纳米颗粒分散于DMSO水溶液，加入SH‑PEG‑NH2，获得纳米粒子Au/Fe3O4@mSiO2/DOX‑SS‑PEG‑NH2；然后采用碳二亚胺法将HA溶于MES溶液，加入EDC和NHS作为偶联剂，加入的Au/Fe3O4@mSiO2/DOX‑SS‑PEG‑NH2。本发明的纳米探针具有MRI、MPI及PAI三种成像功能和化疗及光热治疗功能，可实现对肿瘤的全面、灵敏、靶向性成像，并能进行药物疗效的实时定量在体监测，在分子水平为肿瘤的精准诊疗开辟了全新领域。

Description

兼具药物控释及成像功能的介孔氧化硅复合体的制备方法
技术领域
本发明属于纳米材料与分子医学技术领域，具体涉及一种复合介孔二氧化硅纳米药物载体及其制备方法。
背景技术
随着肿瘤诊断和治疗技术的提高，精准治疗及监测治疗反应对于提高疗效越来越重要。目前临床常用的肿瘤诊断和评估方法主要有CT、磁共振(MRI)、超声等，但存在敏感性及特异性低、不能实时监测等缺点。多模态影像技术可以克服现有手段的局限性，实现无创、实时、定量、特异性检测，提供更加全面精确的信息并指导治疗。化疗是抗肿瘤治疗的重要手段，但传统化疗存在副反应大，缺乏靶向性，易产生多药耐药以及治疗方式单一等缺点。近年来，光热治疗、靶向治疗、纳米药物控释等研究领域的发展，为解决以上问题提供了新的思路。
目前，吴春英等人发明的药物载体及其制备方法和药物组合物及其应用(CN103893764A)，该发明将金纳米棒包裹介孔二氧化硅装载药物，利用近红外激光激发后实现药物释放和热疗。但由于金纳米粒子不具有磁性，不能进行无创的磁粒子实时药物监测，难以进行疗效实时监控；且药物控释需借助激光激发，实施复杂，实际应用中存在难度。
发明内容
针对现有技术中存在的上述不足，本发明提供了一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法。
为了解决上述技术问题，本发明采用了如下技术方案：
兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，该方法包括如下步骤：
(1)Au/Fe3O4@mSiO2-SH分子探针的制备
首先，Au纳米颗粒的制备：将1ml HAuCl4·4H2O(1wt％)溶液和2ml柠檬酸三钠(38.8mM)溶液溶于超纯水(90ml)中，磁力搅拌1分钟；然后缓慢加入1～2mL NaBH4溶液(0.075wt％)，继续搅拌，直到溶液变成酒红色，不再变化；经超纯水三次洗涤后获得Au纳米颗粒；
其次，制备Au/Fe3O4壳核结构纳米颗粒：将100mg的氨基修饰的四氧化三铁(Fe3O4-NH2)纳米颗粒分散于100mL纯水中，加入1～1.5ml Au纳米粒子溶液(10mg/ml)，室温下搅拌2小时后经磁性分离，用去离子水洗涤三次，加入1～2ml 0.1M的HAuCl4·4H2O和10ml 0.2M羟胺水溶液，反应2小时后，将所得纳米粒子经磁性分离，用去离子水洗涤三次，即成功制备Au/Fe3O4壳核结构纳米颗粒；
然后，应用反相微乳液法制备Au/Fe3O4@mSiO2-SH纳米颗粒：取0.1g上述制备粒子分散到30mL超纯水中，超声30min，分散均匀后倒入三口烧瓶中，加入50mL水，40mL乙醇，1.5mL氨水，0.2～0.3mL正硅酸四乙酯(TEOS)，搅拌反应10～12h后，然后加入75mg十六烷基三甲基溴化铵(CTAB)，搅拌1h，加入1mL氨水，搅拌10min，混合均匀后，缓慢加入TEOS乙醇溶液，再加入0.01～0.02mL 3-巯丙基三乙氧基硅烷(MPTES)，搅拌反应12h后将产物磁分离，用乙醇洗涤三次以除去多余的TEOS和少量的CTAB；然后在80℃的盐酸乙醇溶液回流搅拌12h，萃取3次，除去粒子中的模板剂CTAB，即可制备得到Au/Fe3O4@mSiO2-SH纳米颗粒；
(2)Au/Fe3O4@mSiO2/DOX-SS-PEG-HA的制备
将30～40mg/mL DOX乙醇溶液或紫杉醇(TAX)乙醇溶液中加入30mgAu/Fe3O4@mSiO2-SH纳米颗粒，搅拌2h，同时防止乙醇挥发，搅拌后，离心分离，将所得纳米颗粒分散于20％DMSO水溶液，超声分散30min后，加入25mgSH-PEG-NH2，反应5h后，离心分离，即可获得纳米粒子Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2；然后采用碳二亚胺法将50mg的HA溶于PH＝5的2mL MES溶液，加入30mg的EDC和20mg的NHS作为偶联剂在室温下活化激活1h，随后缓慢加入50mg的Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2，调节PH至8，反应4h后离心，去离子水洗涤三次，即得多功能靶向药物控释分子探针Au/Fe3O4@mSiO2/DOX-SS-PEG-HA。
进一步，含荧光(FITC)Au/Fe3O4@mSiO2-SH纳米颗粒，在加入MPTES时，同时加入0.1-0.2mL 3-氨丙基三乙氧基硅烷(APTES)-异硫氰酸荧光素(FITC)反应前体。
进一步，在步骤(1)中，氨水的质量分数28％。
进一步，在步骤(1)中，TEOS乙醇溶液为0.2～0.3ml TEOS分散于20mL乙醇所形成的溶液。
与现有技术相比，本发明具有如下优点：
1、本发明通过整合多种成像方式实现肿瘤诊断及体内药物监控，并减少多药耐药获得高效精准治疗，达到肿瘤多模态诊断、监测疗效及多种治疗方式协同治疗的目的。
2、本发明将结合传统磁共振技术与新兴磁粒子成像、光声成像手段，实现多模态成像及疗效实时定量检测；并实现光热及化学协同治疗；并利用细胞内部氧化还原反应实现药物控释。
3、构建高效、特性强、灵敏度高、无创的多功能靶向药物控释分子探针；以Au/Fe3O4为核，以介孔二氧化硅为载体，制备壳核结构纳米颗粒，以CD44受体为靶点，合成多功能靶向分子探针，对其靶向能力、成像效果及脏器分布进行深入研究，实现肿瘤早期精确诊断多模态成像(磁共振成像、磁粒子成像、光声成像)及体内各脏器药物定量分布监测。
4、壳核结构介孔二氧化硅孔道内封装化疗药物，其表面以二硫键连接PEG-透明质酸实现体内长循环及可控性释放。联合激光照射Au纳米粒子实现光热治疗与化疗的协同治疗。
5、本发明提出了一种新的集靶向诊疗为一体的多模态纳米探针的概念，该纳米探针具有MRI、MPI及PAI三种成像功能，可实现对肿瘤的全面、灵敏、靶向性成像，并能进行药物疗效的实时定量在体监测，在分子水平为肿瘤的精准诊疗开辟了全新领域。
6、本发明构建了多种功能相结合的且具有临床转化前景的创新型靶向诊疗分子探针。采用的Au粒子可以进行光热治疗；Fe3O4可实现多种成像及实时疗效监控；介孔二氧化硅可以封装药物并增强Fe3O4的MRI成像信号；二氧化硅表面修饰的SS-PEG-HA，实现了靶向化疗药物控释及延长体内循环。
7、药物靶向控释系统为解决化疗药物限制性毒性问题提供了新的解决思路。光热治疗与化疗相结合，起到协同增效作用，促进肿瘤多学科治疗的发展。
具体实施方式
下面结合具体实施方式对本发明作进一步详细地描述。
实施例1
本实施例1提供了一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，该方法包括以下步骤：
(1)Au/Fe3O4核的制备
Fe3O4纳米颗粒的制备。将1g FeCl3·6H2O和0.37g FeCl2·4H2O用20mL通氮除氧去离子水混合；取130mL去离子水在250mL的圆底烧瓶中通氮除氧，加入12.5mL的浓度为25-28％的浓氨水，在剧烈搅拌下迅速向其中倒入上述的铁盐混合溶液，在氮气条件下反应l h(80℃)；反应完毕后，用永磁铁从反应溶液分离Fe3O4磁性纳米粒子，用甲醇洗涤三次，分散在50mL甲苯中。然后，将(3-氨基丙基)三甲氧基硅烷(APTES)(25μL)加入到12.5mL上述Fe3O4溶液中，超声分散30min，在60℃下反应4h后，用磁场分离，甲醇洗涤三次，除去多余的APTMS和甲苯，分散在甲醇中。
Au纳米颗粒的制备。将1ml HAuCl4·4H2O(1wt％)溶液和2ml柠檬酸三钠(38.8mM)溶液溶于超纯水(90ml)中，磁力搅拌1分钟；然后缓慢加入1mL NaBH4溶液(0.075wt％)，继续搅拌，直到溶液变成酒红色，不再变化；经超纯水三次洗涤后获得Au纳米颗粒。
Au/Fe3O4壳核结构纳米颗粒的制备。将100mg的氨基修饰的四氧化三铁(Fe3O4-NH2)纳米颗粒分散于100mL纯水中，加入1ml Au纳米粒子溶液(10mg/ml)，室温下搅拌2小时后经磁性分离，用去离子水洗涤三次，加入1ml0.1M的HAuCl4·4H2O和10ml 0.2M羟胺水溶液，反应2小时后，将所得纳米粒子经磁性分离，用去离子水洗涤三次，即成功制备Au/Fe3O4壳核结构纳米颗粒。
(2)Au/Fe3O4@mSiO2-SH纳米颗粒的制备
取0.1g上述制备粒子分散到30mL超纯水中，超声30min，分散均匀后倒入三口烧瓶中，加入50mL水，40mL乙醇，1.5mL氨水(质量分数28％)，0.2mL正硅酸四乙酯(TEOS)，搅拌反应10h后，然后加入75mg十六烷基三甲基溴化铵(CTAB)，搅拌1h，加入1mL氨水，搅拌10min，混合均匀后，缓慢加入TEOS乙醇溶液(0.2ml TEOS分散于20mL乙醇)，再加入0.01mL 3-巯丙基三乙氧基硅烷(MPTES)，搅拌反应12h后将产物磁分离，用乙醇洗涤三次以除去多余的TEOS和少量的CTAB；然后在盐酸乙醇溶液(80℃)回流搅拌12h，萃取3次，除去粒子中的模板剂CTAB，即可制备得到Au/Fe3O4@mSiO2-SH纳米颗粒。
(3)Au/Fe3O4@mSiO2/DOX-SS-PEG-HA的制备
将30mg/mL阿霉素(DOX)乙醇溶液中加入30mg Au/Fe3O4@mSiO2-SH纳米颗粒，搅拌2h(同时防止乙醇挥发)后，离心分离，将所得纳米颗粒分散于20％DMSO水溶液，超声分散30min后，加入25mg SH-PEG-NH2，反应5h后，离心分离，即可获得纳米粒子Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2。然后采用碳二亚胺法将HA(50mg)溶于2mL MES溶液(PH＝5)，加入EDC(30mg)和NHS(20mg)作为偶联剂在室温下活化激活1h，随后缓慢加入50mg的Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2，调节PH至8，反应4h后离心，去离子水洗涤三次，即得多功能靶向药物控释分子探针Au/Fe3O4@mSiO2/DOX-SS-PEG-HA。
该兼具药物控释及成像功能的介孔二氧化硅复合体，具体是指：Au/Fe3O4纳米颗粒作为内核实现磁共振成像、磁粒子成像及光声成像，同时Au纳米颗粒在激光照射下实现光热治疗；壳层介孔二氧化硅纳米孔道内封装多柔比星(DOX)，其表面修饰二硫键-PEG，PEG可用于在运输过程中密封药物及延长体内循环时间，在靶向肿瘤细胞后，利用二硫桥骨架结构在肿瘤细胞内的谷胱甘肽作用下进行氧化还原反应实现药物胞内控释。
实施例2
本实施例2提供了一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，该方法包括以下步骤：
(1)Au/Fe3O4核的制备
Fe3O4纳米颗粒的制备。将1g FeCl3·6H2O和0.37g FeCl2·4H2O用30mL通氮除氧去离子水混合；取160mL去离子水在250mL的圆底烧瓶中通氮除氧，加入15mL的浓度为25-28％的浓氨水，在剧烈搅拌下迅速向其中倒入上述的铁盐混合溶液，在氮气条件下反应2h(80℃)；反应完毕后，用永磁铁从反应溶液分离Fe3O4磁性纳米粒子，用甲醇洗涤三次，分散在60mL甲苯中。然后，将(3-氨基丙基)三甲氧基硅烷(APTES)(20μL)加入到12.5mL上述Fe3O4溶液中，超声分散30min，在60℃下反应4h后，用磁场分离，甲醇洗涤三次，除去多余的APTMS和甲苯，分散在甲醇中。
Au纳米颗粒的制备。将1ml HAuCl4·4H2O(1wt％)溶液和2ml柠檬酸三钠(38.8mM)溶液溶于超纯水(90ml)中，磁力搅拌1分钟；然后缓慢加入2mL NaBH4溶液(0.075wt％)，继续搅拌，直到溶液变成酒红色，不再变化；经超纯水三次洗涤后获得Au纳米颗粒。
Au/Fe3O4壳核结构纳米颗粒的制备。将100mg的氨基修饰的四氧化三铁(Fe3O4-NH2)纳米颗粒分散于100mL纯水中，加入1.5ml Au纳米粒子溶液(10mg/ml)，室温下搅拌2小时后经磁性分离，用去离子水洗涤三次，加入2ml0.1M的HAuCl4·4H2O和10ml 0.2M羟胺水溶液，反应2小时后，将所得纳米粒子经磁性分离，用去离子水洗涤三次，即成功制备Au/Fe3O4壳核结构纳米颗粒。
(2)Au/Fe3O4@mSiO2-SH纳米颗粒的制备
取0.1g上述制备粒子分散到30mL超纯水中，超声30min，分散均匀后倒入三口烧瓶中，加入50mL水，40mL乙醇，1.5mL氨水(质量分数28％)，0.3mL正硅酸四乙酯(TEOS)，搅拌反应12h后，然后加入75mg十六烷基三甲基溴化铵(CTAB)，搅拌1h，加入1mL氨水，搅拌10min，混合均匀后，缓慢加入TEOS乙醇溶液(0.3ml TEOS分散于20mL乙醇)，再加入0.02mL 3-巯丙基三乙氧基硅烷(MPTES)，搅拌反应12h后将产物磁分离，用乙醇洗涤三次以除去多余的TEOS和少量的CTAB；然后在盐酸乙醇溶液(80℃)回流搅拌12h，萃取3次，除去粒子中的模板剂CTAB，即可制备得到Au/Fe3O4@mSiO2-SH纳米颗粒。
(3)Au/Fe3O4@mSiO2/DOX-SS-PEG-HA的制备
将40mg/mL阿霉素(DOX)乙醇溶液中加入30mg Au/Fe3O4@mSiO2-SH纳米颗粒，搅拌2h(同时防止乙醇挥发)后，离心分离，将所得纳米颗粒分散于20％DMSO水溶液，超声分散30min后，加入25mg SH-PEG-NH2，反应5h后，离心分离，即可获得纳米粒子Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2。然后采用碳二亚胺法将HA(50mg)溶于2mL MES溶液(PH＝5)，加入EDC(30mg)和NHS(20mg)作为偶联剂在室温下活化激活1h，随后缓慢加入50mg的Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2，调节PH至8，反应4h后离心，去离子水洗涤三次，即得多功能靶向药物控释分子探针Au/Fe3O4@mSiO2/DOX-SS-PEG-HA。
实施例3
本实施例3提供了一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，该方法包括以下步骤：
(1)Au/Fe3O4核的制备
Fe3O4纳米颗粒的制备。将1g FeCl3·6H2O和0.37g FeCl2·4H2O用20mL通氮除氧去离子水混合；取130mL去离子水在250mL的圆底烧瓶中通氮除氧，加入12.5mL的浓度为25-28％的浓氨水，在剧烈搅拌下迅速向其中倒入上述的铁盐混合溶液，在氮气条件下反应l h(80℃)；反应完毕后，用永磁铁从反应溶液分离Fe3O4磁性纳米粒子，用甲醇洗涤三次，分散在50mL甲苯中。然后，将(3-氨基丙基)三甲氧基硅烷(APTES)(25μL)加入到12.5mL上述Fe3O4溶液中，超声分散30min，在60℃下反应4h后，用磁场分离，甲醇洗涤三次，除去多余的APTMS和甲苯，分散在甲醇中。
Au纳米颗粒的制备。将1ml HAuCl4·4H2O(1wt％)溶液和2ml柠檬酸三钠(38.8mM)溶液溶于超纯水(90ml)中，磁力搅拌1分钟；然后缓慢加入1mL NaBH4溶液(0.075wt％)，继续搅拌，直到溶液变成酒红色，不再变化；经超纯水三次洗涤后获得Au纳米颗粒。
Au/Fe3O4壳核结构纳米颗粒的制备。将100mg的氨基修饰的四氧化三铁(Fe3O4-NH2)纳米颗粒分散于100mL纯水中，加入1ml Au纳米粒子溶液(10mg/ml)，室温下搅拌2小时后经磁性分离，用去离子水洗涤三次，加入1ml0.1M的HAuCl4·4H2O和10ml 0.2M羟胺水溶液，反应2小时后，将所得纳米粒子经磁性分离，用去离子水洗涤三次，即成功制备Au/Fe3O4壳核结构纳米颗粒。
(2)Au/Fe3O4@mSiO2-SH纳米颗粒的制备
取0.1g上述制备粒子分散到30mL超纯水中，超声30min，分散均匀后倒入三口烧瓶中，加入50mL水，40mL乙醇，1.5mL氨水(质量分数28％)，0.2mL正硅酸四乙酯(TEOS)，搅拌反应10h后，然后加入75mg十六烷基三甲基溴化铵(CTAB)，搅拌1h，加入1mL氨水，搅拌10min，混合均匀后，缓慢加入TEOS乙醇溶液(0.2ml TEOS分散于20mL乙醇)，再加入0.01mL 3-巯丙基三乙氧基硅烷(MPTES)，搅拌反应12h后将产物磁分离，用乙醇洗涤三次以除去多余的TEOS和少量的CTAB；然后在盐酸乙醇溶液(80℃)回流搅拌12h，萃取3次，除去粒子中的模板剂CTAB，即可制备得到Au/Fe3O4@mSiO2-SH纳米颗粒。
(3)Au/Fe3O4@mSiO2/TAX-SS-PEG-HA的制备
将30mg/mL紫杉醇(TAX)乙醇溶液中加入30mg Au/Fe3O4@mSiO2-SH纳米颗粒，搅拌2h(同时防止乙醇挥发)后，离心分离，将所得纳米颗粒分散于20％DMSO水溶液，超声分散30min后，加入25mg SH-PEG-NH2，反应5h后，离心分离，即可获得纳米粒子Au/Fe3O4@mSiO2/TAX-SS-PEG-NH2。然后采用碳二亚胺法将HA(50mg)溶于2mL MES溶液(PH＝5)，加入EDC(30mg)和NHS(20mg)作为偶联剂在室温下活化激活1h，随后缓慢加入50mg的Au/Fe3O4@mSiO2/TAX-SS-PEG-NH2，调节PH至8，反应4h后离心，去离子水洗涤三次，即得多功能靶向药物控释分子探针Au/Fe3O4@mSiO2/TAX-SS-PEG-HA。
最后说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的宗旨和范围，其均应涵盖在本发明的权利要求范围当中。

Claims (4)

1.兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，其特征在于，该方法包括如下步骤：
(1)Au/Fe3O4@mSiO2-SH分子探针的制备
首先，Au纳米颗粒的制备：将1ml HAuCl4·4H2O(1wt％)溶液和2ml柠檬酸三钠(38.8mM)溶液溶于超纯水(90ml)中，磁力搅拌1分钟；然后缓慢加入1～2mL NaBH4溶液(0.075wt％)，继续搅拌，直到溶液变成酒红色，不再变化；经超纯水三次洗涤后获得Au纳米颗粒；
其次，制备Au/Fe3O4壳核结构纳米颗粒：将100mg的氨基修饰的四氧化三铁(Fe3O4-NH2)纳米颗粒分散于100mL纯水中，加入1～1.5ml Au纳米粒子溶液(10mg/ml)，室温下搅拌2小时后经磁性分离，用去离子水洗涤三次，加入1～2ml 0.1M的HAuCl4·4H2O和10ml 0.2M羟胺水溶液，反应2小时后，将所得纳米粒子经磁性分离，用去离子水洗涤三次，即成功制备Au/Fe3O4壳核结构纳米颗粒；
然后，应用反相微乳液法制备Au/Fe3O4@mSiO2-SH纳米颗粒：取0.1g上述制备粒子分散到30mL超纯水中，超声30min，分散均匀后倒入三口烧瓶中，加入50mL水，40mL乙醇，1.5mL氨水，0.2～0.3mL正硅酸四乙酯(TEOS)，搅拌反应10～12h后，然后加入75mg十六烷基三甲基溴化铵(CTAB)，搅拌1h，加入1mL氨水，搅拌10min，混合均匀后，缓慢加入TEOS乙醇溶液，再加入0.01～0.02mL 3-巯丙基三乙氧基硅烷(MPTES)，搅拌反应12h后将产物磁分离，用乙醇洗涤三次以除去多余的TEOS和少量的CTAB；然后在80℃的盐酸乙醇溶液回流搅拌12h，萃取3次，除去粒子中的模板剂CTAB，即可制备得到Au/Fe3O4@mSiO2-SH纳米颗粒；
(2)Au/Fe3O4@mSiO2/DOX-SS-PEG-HA的制备
将30～40mg/mL DOX乙醇溶液或紫杉醇(TAX)乙醇溶液中加入30mgAu/Fe3O4@mSiO2-SH纳米颗粒，搅拌2h，同时防止乙醇挥发，搅拌后，离心分离，将所得纳米颗粒分散于20％DMSO水溶液，超声分散30min后，加入25mg SH-PEG-NH2，反应5h后，离心分离，即可获得纳米粒子Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2；然后采用碳二亚胺法将50mg的HA溶于PH＝5的2mL MES溶液，加入30mg的EDC和20mg的NHS作为偶联剂在室温下活化激活1h，随后缓慢加入50mg的Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2，调节PH至8，反应4h后离心，去离子水洗涤三次，即得多功能靶向药物控释分子探针Au/Fe3O4@mSiO2/DOX-SS-PEG-HA。
2.如权利要求1所述的一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，其特征在于，含荧光(FITC)Au/Fe3O4@mSiO2-SH纳米颗粒，在加入MPTES时，同时加入0.1-0.2mL3-氨丙基三乙氧基硅烷(APTES)-异硫氰酸荧光素(FITC)反应前体。
3.如权利要求1所述的一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，其特征在于，在步骤(1)中，氨水的质量分数28％。
4.如权利要求1所述的一种兼具药物控释及成像功能的介孔氧化硅复合体的制备方法，其特征在于，在步骤(1)中，TEOS乙醇溶液为0.2～0.3ml TEOS分散于20mL乙醇所形成的溶液。
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