Nano-erythrocyte membrane-chaperoned 5-fluorouracil liposomes as biomimetic delivery platforms to target hepatocellular carcinoma cell lines

Abstract

Nano-erythrocyte coating has been developed as an interesting biomimetic platform to provide hybrid nano-carriers with innate functions to target liver cancer. This goal was achieved by coating nano-erythrocyte membranes (NEMs) onto 5-fluorouracil (5-FU)-loaded liposomes (LPs) to produce NEM-5-FU-LPs. This framework is used to promote the escape of 5-FU-LPs from degradation during systemic circulation. NEMs were obtained by hypotonic lysis of erythrocytes to produce ghost erythrocytes (GEs) followed by extrusion through polycarbonate membranes. Chimeric NEM-5-FU-LPs were fabricated via the fusion of NEMs and artificial LPs. The resultant chaperoned LPs were characterized based on particle size, morphology, entrapment efficiency (EE %), stability, protein content and phosphatidylserine exposure and their in vitro release profiles and cytotoxic efficacy were also determined. The present results revealed that 5-FU-LPs, NEM-5-FU and NEM-5-FU-LPs exhibited nanosize, spherical shapes and unimodal size distributions <0.3. In addition, the vesicles presented a zeta potential with EE% of 24.6–30.7% and an appropriate stability for 3 weeks. NEM-5-FU-LPs retained the erythrocyte membrane proteins as confirmed by PAGE and displayed a sustained release profile up to 48 h when compared to NEM-5-FU and the 5-FU solution. Moreover, hybrid NEM-5-FU-LPs induced a late cytotoxic effect after 48 h compared to the other formulations. Thus, mantling of 5-FU-LPs by NEMs could enhance vesicle controllability and their targetability to liver cancer cells.