Copper arsenite-complexed Fenton-like nanoparticles as oxidative stress-amplifying anticancer agents.

We report copper(II) arsenite (CuAS)-integrated polymer micelles (CuAS-PMs) as a new class of Fenton-like catalytic nanosystem that can display reactive oxygen species (ROS)-manipulating anticancer therapeutic activity. CuAS-PMs were fabricated through metal-catechol chelation-based formation of the CuAS complex on the core domain of poly (ethylene glycol)-b-poly(3,4-dihydroxy-L-phenylalanine) (PEG-PDOPA) copolymer micelles. CuAS-PMs maintained structural robustness under serum conditions. The insoluble state of the CuAS complex was effectively retained at physiological pH, whereas, at endosomal pH, the CuAS complex was ionized to release arsenite and cuprous Fenton catalysts (Cu+ ions). Upon endocytosis, CuAS-PMs simultaneously released hydrogen peroxide (H2O2)-generating arsenite and Fenton-like reaction-catalyzing Cu+ ions in cancer cells, which synergistically elevated the level of highly cytotoxic hydroxyl radicals (•OH), thereby preferentially killing cancer cells. Animal experiments demonstrated that CuAS-PMs could effectively suppress the growth of solid tumors without systemic in vivo toxicity. The design rationale of CuAS-PMs may provide a promising strategy to develop diverse oxidative stress-amplifying agents with great potential in cancer-specific therapy.

Mussel-inspired poly(L-DOPA)-templated mineralization for calcium phosphate-assembled intracellular nanocarriers.

We developed a calcium phosphate (CaP)-assembled polymer nanocarrier for intracellular doxorubicin (DOX) delivery based on a mussel-inspired mineralization approach. A DOX-loaded core-shell polymer nanoparticle (DOX-NP) consisting of a poly(3,4-dihydroxy-l-phenylalanine) (PDOPA) core and a poly (ethylene glycol) (PEG) shell was utilized as a nanotemplate for CaP mineralization. The mean hydrodynamic diameter of the DOX-loaded CaP-mineralized polymer nanoparticles (DOX-CaP-NPs) was 154.3nm. Energy-dispersive X-ray spectroscopy confirmed that the DOX-CaP-NPs contained substantial amounts of Ca and P, elements found only in the CaP mineral. The loading efficiency and content of DOX, estimated by fluorescence spectroscopy, were 54.0% and 10.8wt%, respectively. The CaP deposited in the PDOPA core domain enabled the DOX-CaP-NPs to maintain a robust structure and effectively inhibit DOX release at extracellular pH, whereas at endosomal pH, the CaP core dissolved to trigger a facilitated DOX release. The DOX-CaP-NPs may serve as robust nanocarriers with a high delivery efficacy for cancer chemotherapy.