Department of Bio-Nano Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
Biomaterials. 2010 Mar;31(8):2302-12. doi: 10.1016/j.biomaterials.2009.11.067. Epub 2009 Dec 11.
Targeted uptake of nanoscale controlled release polymer micelles encapsulated with drugs represents a potential powerful therapeutic technology. Herein we reported the development of anti-HIF-1alpha antibody-conjugated unimolecular polymer nano micelles filled with Paclitaxel for cancer targeting therapy. Pluronic triblock copolymers(Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), PEO-block-PPO-block-PEO) P123 were functionalized with terminal carboxylic groups, and were characterized by infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and differential scanning calorimetric (DSC). The amphiphilic copolymer nano micelles encapsulated with Paclitaxel were fabricated by self-assembly means, and then were conjugated with anti-HIF-1alpha antibody, the resultant anti-HIF-1alpha conjugated nano micelles filled with PTX (anti-HIF-1alpha-NMs-PTX nanocomposites) were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells, these treated cells were analyzed by MTT and cell-ELISA. The nanocomposites composed of anti-HIF-1alpha conjugated nano micelles filled with CdTe quantum dots were also prepared, and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells for 24 h, then were observed by fluorescent microscope. Results showed that the anti-HIF-1alpha-NMs-PTX nanocomposites were successfully prepared, bound with stomach cancer MGC-803 cells specifically, were internalized, and released PTX inside cancer cells, and selectively killed cancer cells. In conclusion, unique anti-HIF-1alpha antibody-conjugated nano micelles filled with Paclitaxel can target and selectively kill cancer cells with over-expression of HIF-1alpha, and has great potential in clinical tumor targeting imaging and therapy.
靶向摄取纳米级控释聚合物胶束包裹的药物代表了一种有潜力的强大治疗技术。本文报道了载紫杉醇的抗 HIF-1α 抗体偶联单分子聚合物纳米胶束的制备及其用于癌症靶向治疗的研究。首先将两亲性嵌段共聚物聚(乙二醇)-嵌段-聚(丙二醇)-嵌段-聚(乙二醇)(Pluronic triblock copolymers,P123)末端羧基化,通过红外(IR)光谱、核磁共振(NMR)、热重分析(TGA)和差示扫描量热法(DSC)对其进行了表征。通过自组装的方法制备载紫杉醇的两亲性嵌段共聚物纳米胶束,然后与抗 HIF-1α 抗体偶联,得到载紫杉醇的抗 HIF-1α 抗体偶联纳米胶束(anti-HIF-1α-NMs-PTX nanocomposites),通过动态光散射(DLS)和透射电子显微镜(TEM)对其进行了表征,并与胃癌 MGC-803 细胞和人正常成纤维细胞(HDF)共孵育,通过 MTT 和细胞酶联免疫吸附实验(cell-ELISA)分析了这些处理后的细胞。还制备了载 CdTe 量子点的抗 HIF-1α 抗体偶联纳米胶束的纳米复合材料,并与胃癌 MGC-803 细胞和 HDF 共孵育 24 h,然后通过荧光显微镜观察。结果表明,成功制备了载紫杉醇的抗 HIF-1α 抗体偶联纳米胶束,该纳米胶束可以特异性地与胃癌 MGC-803 细胞结合,被细胞内化,并在癌细胞内释放紫杉醇,从而选择性地杀伤癌细胞。总之,载紫杉醇的独特的抗 HIF-1α 抗体偶联纳米胶束可以靶向并选择性杀伤过表达 HIF-1α 的癌细胞,在临床肿瘤靶向成像和治疗方面具有巨大的应用潜力。
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