Surface modification of liposomes with rhodamine-123-conjugated polymer results in enhanced mitochondrial targeting

Abstract

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.

Keywords::

• Liposomes
• rhodamine-123
• amphiphilic polymer
• mitochondrial targeting
• drug delivery
• paclitaxel
• cytotoxicity

Acknowledgement

This work was supported by the NIH grant # RO1 CA128486 to Vladimir P. Torchilin.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.