Tumor-Targeted Paclitaxel Delivery and Enhanced Penetration Using TAT-Decorated Liposomes Comprising Redox-Responsive Poly(Ethylene Glycol)

摘要: ABSTRACT To combine the advantage of poly(ethylene gylcol) (PEG) for longer circulation and cell-penetrating peptides (CPPs) efficient cellular uptake, paclitaxel (PTX)-loaded liposomes functionalized with TAT, most frequently used CPP, cleavable PEG via a redox-responsive disulfide linker (PTX-C-TAT-LP) were successfully developed here. Under physiological conditions, TAT was shielded by layer exhibited long blood circulation. At tumor site, could be detached in presence exogenous reducing agent [glutathione (GSH)] exposed to facilitate cell internalization. In GSH, liposomal vesicle C-TAT-LP showed increased uptake improved three-dimensional spheroids penetration vitro compared analogous stable liposomes. achieved enhanced distribution demonstrated superior delivery efficiency vivo . PTX-C-TAT-LP GSH strongly inhibited proliferation murine melanoma B16F1 cells inhibition rate being 69.4% on B16F1-bearing mice. addition, serum aspartate transaminase level, alanine creatine kinase level almost completely within normal range group, revealing had no obvious drug-related adverse events liver heart. Taken together, is promising tumor-targeting drug carrier. © 2014 Wiley Periodicals, Inc. American Pharmacists Association.