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利用荧光显微镜追踪脂质体和胶束对细胞的靶向作用及其细胞内命运。

Fluorescence microscopy to follow the targeting of liposomes and micelles to cells and their intracellular fate.

作者信息

Torchilin Vladimir P

机构信息

Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.

出版信息

Adv Drug Deliv Rev. 2005 Jan 2;57(1):95-109. doi: 10.1016/j.addr.2004.06.002.

Abstract

Fluorescence microscopy may provide important information regarding interactions between nanoparticulate drugs carriers, such as liposomes and micelles, with target cells as well as their intracellular fate. Current paper describes various applications of fluorescence microscopy to investigate specific targeting of antibody-modified drug carriers to cancer cells. The enhanced antibody-mediated targeting of drug-loaded immunomicelles confirmed by fluorescence microscopy resulted in enhanced cancer cell killing compared to free drug or drug-loaded nontargeted micelles. Fluorescence microscopy was also used to prove the endosomal escape of properly assembled polymeric micelles (based on polyethylene glycol-phosphatidylethanolamine conjugate, PEG-PE) containing various additives destabilizing the endosomal membrane. When loaded with the anticancer drug (paclitaxel or vitamin K3), such micelles demonstrate increased cytotoxicity. Fluorescence microscopy was also applied to investigate the capture of cell-penetrating TAT peptide-modified liposomes by various cells and stability and intracellular trafficking of captured TAT-liposomes inside cells. It was also used to confirm the successful transfection of cells with TAT-liposomes bearing the plasmid encoding for the Green Fluorescent Protein (GFP).

摘要

荧光显微镜可以提供有关纳米颗粒药物载体(如脂质体和胶束)与靶细胞之间相互作用及其细胞内命运的重要信息。本文描述了荧光显微镜在研究抗体修饰的药物载体对癌细胞的特异性靶向方面的各种应用。荧光显微镜证实,与游离药物或载药非靶向胶束相比,抗体介导的载药免疫胶束靶向增强,导致癌细胞杀伤增强。荧光显微镜还用于证明含有各种破坏内体膜稳定性添加剂的适当组装的聚合物胶束(基于聚乙二醇 - 磷脂酰乙醇胺共轭物,PEG - PE)的内体逃逸。当载有抗癌药物(紫杉醇或维生素K3)时,此类胶束表现出增强的细胞毒性。荧光显微镜还用于研究各种细胞对穿膜TAT肽修饰的脂质体的摄取以及捕获的TAT - 脂质体在细胞内的稳定性和细胞内运输。它还用于确认携带编码绿色荧光蛋白(GFP)质粒的TAT - 脂质体成功转染细胞。

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