Acid-responsive PEGylated doxorubicin prodrug nanoparticles for neuropilin-1 receptor-mediated targeted drug delivery

摘要: Self-assembled prodrug nanoparticles have demonstrated great promise in cancer chemotherapy. In the present study, we developed a new kind of for targeted drug delivery. PEGylated doxorubicin conjugate with an acid-cleavable cis-aconityl spacer was prepared. Then it functionalized tumor-penetrating peptide, Cys-Arg-Gly-Asp-Lys (CRGDK), providing specific binding ability to neurophilin-1 receptor. acid mediums, could be released from accumulative release around 60% through acid-triggered hydrolysis bond and nanoparticle disassembly. Whereas, slow under neutral pH less than 16%. cell culture tests, our showed enhanced endocytosis cytotoxicity cells including HepG2, MCF-7 MDA-MB-231 cells, but lower human cardiomyocyte H2C9. animal experiments, were intravenously injected into Balb/c nude mice bearing tumors. Enhanced penetration accumulation tumors, accompanying rapid early tumor-binding behavior, observed after intravenous injection peptide modified nanoparticles. These data suggests that acid-sensitive tumor-targeting may efficient delivery system