A cancer cell membrane coated nanoparticles-based gene delivery system for enhancing cancer therapy

Gene therapy is a superior therapeutic means in cancer therapy. However, the instability of nucleic acid and the lack of suitable delivery carrier greatly restricts its further development and application. Herein, we coupled low molecular weight polyethyleneimine (LMW PEI) through disulfide bonds, then modified it with manganese dioxide (MnO₂) nanosheets and nuclear localization signal peptide (NLS), as a p53 gene carrier, and finally coated it with B16F10 cell membrane to construct a novel gene-carrier system CM@MnO₂-PEI-NLS-ss/p53 (M@MPNs/p53). Tumor cell membrane coating endows nanoparticles with homotypic targeting and immune escape capabilities, disulfide-crosslinked LMW-PEI has high transfection efficiency and low toxicity, and NLS peptides enhance nuclear delivery and improve p53 gene delivery efficiency; meanwhile, MnO₂ nanosheets oxidize high intracellular concentration of glutathione (GSH), sensitizing p53 gene-mediated antitumor therapy. The results showed that the novel biofilm-camouflaged M@MPNs/p53 nanoparticles had a highly specific targeting effect on homologous cancer cells and could effectively inhibit tumor growth in vitro and in vivo. Besides, MnO₂ loading improved p53-mediated tumor regression. This novel gene delivery platform is of great significance in improving gene delivery efficiency and enhancing anti-tumor therapy.