RESUMO
Poor antitumor drug penetration into tumor tissues is a global challenge in clinical cancer treatment. Here, we reported a smart multistage "Trojan Horse"-inspired bovine serum albumin (BSA)-coated liposome (HBM), including the mimics of capsid and secondary BSA-coated polymeric nanoparticles (NPs) for enhancing tumor penetration and antitumor efficacy. These drug-loaded polymeric NPs possess a capsid-like component, a well-distributed nanostructure (size: 190.1 ± 4.98 nm, PDI: 0.259), and an excellent drug loading content (15.85 ± 1.36%). Meaningfully, after the smart multistage BSA-coated liposome targeted the tumor tissue, the mimics of capsid were "taken off" under the condition of tumor-specific enzymes, releasing "Heart" BSA-modified secondary NPs to increase the ability to penetrate tumor cells for enhancing antitumor efficacy. As expected, the HBM efficiently achieves high drug penetration into PAN02 tumor cells. Moreover, compared to free DOX and HM (HBM without BSA) NPs, DOX/HBM NPs exhibited the strongest tumor penetration and the highest cytotoxicity against PAN02 tumor cells both in vitro (IC50 = 0.141 µg/mL) and in vivo. This smart multistage "Trojan Horse"-inspired BSA-coated liposome should provide a new hathpace for further development of polymeric NPs in clinical treatment.
