Targeted delivery of cargoes into a murine solid tumor by a cell-penetrating peptide and cleavable poly(ethylene glycol) comodified liposomal delivery system via systemic administration.

A liposomal delivery system with a high efficiency of accumulation in tumor tissue and then transportation of the cargo into tumor cells was developed here and evaluated via systemic administration. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)2000 (DSPE-PEG2000)-TAT and protective DSPE-PEG2000 modified liposomes possessing good stability in 50% FBS (fetal bovine serum) and good uptake efficiency were used as the basic formulation (TAT-SL; SL = stealth liposome), and then longer cysteine (Cys)-cleavable PEG5000 was incorporated to modulate the function of TAT. All of the formulations to be used in vivo had sizes in a range of 80–100 nm and were stable in the presence of 50% FBS. Optical imaging showed that the incorporation of cleavable PEG5000 into TAT-SL (i.e., C-TAT-SL) led to much more tumor accumulation and much less liver distribution compared with TAT-SL. The in vivo delivery profiles of C-TAT-SL were investigated using DiD as a fluorescent probe. Confocal laser scanning mic...