血小板膜伪装介孔聚多巴胺纳米药物传递系统的制备及应用

Preparation and Application of mesoporous Polydopamine Nano-drug delivery system camouflaged by platelet membrane

摘要:

三甲基苯为模板剂，以三嵌段共聚物Pluronic F127（EO 106 PO 70 EO 106）为乳液液滴稳定剂，以乙醇为助溶剂和催化剂，通过一锅法制备具有介孔结构的聚以三甲基苯为模板剂，以三嵌段共聚物Pluronic F127（EO 106 PO 70 EO 106）为乳液液滴稳定剂，以乙醇为助溶剂和催化剂，通过一锅法制备具有介孔结构的聚多巴胺纳米粒子（MPDA NPs）。通过静电吸附负载盐酸阿霉素（DOX），通过血小板膜（PLTM）仿生伪装得到PLTM-DOX@MPDA纳米颗粒。采用TEM、纳米粒度分析仪、BET和UV-Vis对纳米粒子的性质、形貌和粒径进行表征。TEM结果表明，MPDA表面具有清晰的介孔结构，经血小板膜包裹后PLTM-DOX@MPDA粒径约为184 nm。BET结果表明，MPDA 孔径主要分布于45 nm左右，孔容为0.6232 m3/g，比表面积高达61.181 m2/g，这样的介孔结构支持MPDA作为高效的药物传递系统。体外释药结果表明，PLTM-DOX@MPDA具有pH响应性控制药物释放，可以实现药物缓释；体外细胞摄取实验结果表明，PLTM-DOX@MPDA可以避免巨噬细胞吞噬并且主动靶向癌细胞；体外细胞毒性实验结果表明，PLTM-DOX@MPDA可显著提高DOX对MDA-MB-231细胞的杀伤作用。

Abstract:

Polydopamine nanoparticles with mesoporous structure (MPDA NPs) were prepared by one-pot method using 1,3,5-trimethylbenzene as template, triblock copolymer PluronicF127 (EO106PO70EO106) as emulsion droplet stabilizer, ethanol as cosolvent and catalyst. Doxorubicin hydrochloride (DOX) was loaded by electrostatic adsorption and the nano drug delivery system was obtained by biomimetic camouflage of platelet membrane. The properties, morphology and particle size of the nanoparticles were characterized by transmission electron microscope, nano particle size analyzer, BET and UV spectrophotometer. The TEM results show that the surface of MPDA had a clear mesoporous structure, and the particle size of PLTM-DOX@MPDA nanoparticles coated by platelet membrane was about 184 nm. The BET results show that the pore size of MPDA was about 45 nm, the pore volume was 0.6232 m3/g, and the specific surface area was as high as 61.181 m2/g. The mesoporous structure supported MPDA as an efficient drug delivery system. The results of drug release in vitro showed that the nano drug delivery system had pH response to control drug release and could achieve sustained drug release. The results of cell uptake assay in vitro show that the nano drug delivery system could avoid phagocytosis of macrophages and actively target cancer cells. The results of cytotoxicity test in vitro showed that the nano-drug delivery system could enhance killing effect of DOX on MDA-MB-231 cells significantly.