Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
J Drug Target. 2011 Aug;19(7):552-61. doi: 10.3109/1061186X.2010.536983. Epub 2011 Feb 25.
A novel mitochondrial-targeted liposomal drug-delivery system was prepared by modification of the liposomal surface with a newly synthesized polymer, rhodamine-123 (Rh123)-PEG-DOPE inserted into the liposomal lipid bilayer. This novel polymer was synthesized by conjugating the mitochondriotropic dye Rh123, with the amphiphilic polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugate. The modified liposomes showed better uptake by cells (HeLa, B16F10) estimated by fluorescence microscopy and FACS analysis. The co-localization study with stained mitochondria as well as with the isolation of mitochondria of the cultured cells after their treatment with Rh123 liposomes showed a high degree of accumulation of the modified liposomes in the mitochondria. We also prepared mitochondrial-targeted and nontargeted paclitaxel (PCL)-loaded liposomes. Mitochondrial-targeted PCL-loaded liposomes demonstrated enhanced cytotoxicity toward cancer cells compared with nontargeted drug-loaded liposomes or free PCL. Thus, Rh123-modified liposomes target mitochondria efficiently and can facilitate the delivery of a therapeutic payload to mitochondria.
一种新型的线粒体靶向脂质体药物传递系统是通过用新合成的聚合物修饰脂质体表面而制备的，该聚合物将罗丹明 123（Rh123）-PEG-DOPE 插入脂质体的脂质双层中。这种新型聚合物是通过将亲脂性的聚乙二醇-磷脂酰乙醇胺（PEG-PE）缀合物与线粒体靶向染料 Rh123 缀合而合成的。通过荧光显微镜和流式细胞术分析估计，修饰后的脂质体显示出更好的细胞摄取。用染色的线粒体以及用 Rh123 脂质体处理后的培养细胞的线粒体分离进行的共定位研究表明，修饰后的脂质体高度积聚在线粒体中。我们还制备了线粒体靶向和非靶向紫杉醇（PCL）负载的脂质体。与非靶向药物负载的脂质体或游离 PCL 相比，线粒体靶向 PCL 负载的脂质体对癌细胞表现出增强的细胞毒性。因此，Rh123 修饰的脂质体能够有效地靶向线粒体，并能够促进治疗有效载荷递送至线粒体。
