摘要Liposomes decorated with tumour-targeting cell-penetrating peptides can enhance specific drug delivery at the tumour site.The TR peptide,c(RGDfK)-AGYLLGHINLHHLAHL(Aib)HHIL,is pH-sensitive and actively targets tumour cells that overexpress integrin receptor αvβ3,such as B16F10 melanoma cells.Liposomes can be modified with the TR peptide by two different methods:utilization of the cysteine residue on TR to link DSPE-PEG2000-Mal contained in the liposome formula(LIPTR)or decoration of TR with a C18 stearyl chain(C18-TR)for direct insertion into the liposomal phospholipid bilayer through electrostatic and hydrophobic interactions(LIPC18-TR).We found that both TR and C18-TR effectively reversed the surface charge of the liposomes when the systems encountered the low pH of the tumour microenvironment,but LIPC18-TR exhibited a greater increase in the charge,which led to higher cellular uptake efficiency.Correspondingly,the IC50 values of PTX-LIPTR and PTX-LIPC18-TR in B1 6F10 cells in vitro were 2.1-fold and 2.5-fold lower than that of the unmodified PTX-loaded liposomes(PTX-LIP),respectively,in an acidic microenvironment(pH 6.3).In B16F10 tumour-bearing mice,intravenous administration of PTX-LIPTR and PTX-LIPC18-TR(8 mg/kg PTX every other day for a total of 4 injections)caused tumour reduction ratios of 39.4％and 56.1％,respectively,compared to 20.8％after PTX-LIP administration.Thus,we demonstrated that TR peptide modification could improve the antitumour efficiency of liposomal delivery systems,with C18-TR presenting significantly better results.After investigating different modification methods,our data show that selecting an adequate method is vital even when the same molecule is used for decoration.