多功能近红外荧光给药复合纳米胶囊的制备与应用

Recently, malignant tumour threatens people's health seriously. As we know, the chemical anti-cancer drugs have played an important role on the therapy of cancers. However, high-dose chemotherapy drugs also have strong side effects on normal tissues. The increasing need for drug delivery systems that improve specificity and activity and at the same time reduce toxicity to ensure maximum treatment safety has led to the development of a great variety of drug vectors. The development of a multifunctional nanocomposite capsule which is capable of targeted and controlled chemotherapy drug release, photothermal therapy, and in-situ monitoring the efficacy of the cancer therapy, is highly desirable. Herein, via a facile strategy, chemotherapy drugs, nanoparticles with NIR photothermal therapy ability, and the nanocrystals with near-infrared (NIR) fluorescence will be encapsulated in the thermoresponsive polymer nanosphere to form the multifunctional nanocapsule. With the guidance of functional peptides bioconjugated onto the surface of the nanospheres, these multifunctional nanocapsules can be targeted to the tumour. Under the NIR (808nm) light irradiation, the photothermal nanoparticles (NPs) will convert light energy into heat, which on the one hand will kill the tumor via the increased temperature, and on the other hand will induce the thermosensitive polymer shell to shrink and the encapsulated drugs will be released. The tumor will be killed by means of both photothermal therapy and chemotherapy. Meanwhile, the fluorescent NPs will emit strong NIR fluorescence with the 808 nm irradiation, which can be utilized for the tumor fluorescence imaging to indicate the tumor size and thus used for the in-situ evaluation of the tumor therapy. It is notable that the NIR has many advantages including low autofluorescence background and high penetration depth, which is highly desirable for the in-vivo imaging. In summary, we hope these researches will find potential applications in the multimodality treatment of tumors and other serious diseases.

恶性肿瘤严重威胁人类健康，大剂量化疗药物对正常组织产生极强毒副作用。探索既能实现抗癌药物的靶向缓释、集化疗与热疗于一体、又能实时观察肿瘤药物疗效的多功能复合纳米抗癌胶囊，意义重大。本项目拟以热敏高分子将抗癌药物（用于肿瘤化疗）、近红外光热转换纳米颗粒（用于近红外光热转换热疗）及近红外荧光纳米晶（用于近红外荧光成像）包覆成多功能复合胶囊，并以功能多肽对胶囊表面进行修饰（用于定向纳米胶囊到达肿瘤部位）。在近红外光（808纳米）照射下，光热转换纳米颗粒可吸收近红外光转变成热，使肿瘤因受热而被杀死；同时，温敏高分子层在受热作用下会收缩，进而将抗癌药物挤出胶囊而产生化疗作用；此外，荧光纳米颗粒则在光照下发射红外荧光，利用红外荧光(无背景荧光干扰、组织穿透深、适合活体成像)可对肿瘤进行荧光成像、实时监控肿瘤大小和抗癌治疗效果。以期为癌症等重大疾病的靶向缓释治疗提供新材料、新技术和新方法。

恶性肿瘤严重威胁人类健康，大剂量化疗药物对正常组织产生极强毒副作用。探索既能实现抗癌药物的靶向缓释、集化疗与热疗于一体、又能实时观察肿瘤药物疗效的多功能复合纳米抗癌胶囊，意义重大。本项目经过4年研究，取得了如下几方面研究成果，（1）构建了19F-MRI成像-光热治疗的多功能纳米探针，成功用于活体肿瘤的19F核磁共振成像及光热治疗，实现“诊断+治疗”一体化。（2）发展了抗癌药物负载型近红外II区荧光多功能纳米探针，提高了药物靶向性，显著降低生物背景荧光干扰，成功用于抗癌药物活体输运的实时荧光成像示踪，实现“诊断+治疗”一体化。（3）发展了用于抗癌的光热控制释放与热成像示踪的多功能纳米胶囊，成功用于抗癌药物的远程光控释放与热成像示踪，实现“诊断+治疗”一体化。（4）发展了高效小分子及团簇荧光纳米探针，成功用于荧光传感与成像分析。在包括J. Am. Chem. Soc.（2篇） Angew. Chem. Int. Ed.（1篇） Nat. Commun.（1篇），Nano Lett.（1篇），Anal. Chem.（6篇）, Chem. Comm.，Nanoscale，Nano Res.等期刊共发表SCI收录论文46篇，获授权发明专利15项。共培养硕士毕业生9人，博士毕业生4人，其中5人次获国家奖学金。

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