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Benzoperylene-grafted and Cu2+ chelated polymeric nanoparticles for GSH depletion and chemodynamic therapy

Polymeric nanoparticles that can respond to a specific tumor microenvironment (TME) show great potential as anticancer agents. In this study, a highly water-soluble polymeric nanoparticle BPP was obtained via atom transfer radical polymerization (ATRP). The strong tendency of self-aggregation of the grafted aromatic benzoperylene facilitated the self-assembly of the polymer into nanoparticles. BPP showed strong excimer emission and could chelate with various metal ions with quenched emission. Cu2+ was then chelated with BPP to form BPC nanoparticles, which were subsequently used as chemodynamic therapy agents. After entering into the cancer cells, BPC could deplete GSH and produce Cu+. Cu+ reacted with intracellular H2O2 and generated toxic hydroxyl radicals (˙OH) via the Fenton-like reaction, which had a fast reaction rate in TME. Because of the high GSH and H2O2 concentrations in tumor cells, BPC NPs exhibited selective cytotoxicity to cancer cells. Additionally, the excimer fluorescence of BPC recovered after entering into the cancer cells, denoting the potential for real time tracking/visualization of drug delivery. The in vivo results also demonstrate that BPC NPs efficiently inhibited tumor growth without obvious systemic toxicity. As a novel Cu2+ chelated polymeric nanomaterial responsive to TME, BPC NPs show excellent potential in chemodynamic cancer therapy.