A solid lipid coated calcium peroxide nanocarrier enables combined cancer chemo/chemodynamic therapy with O2/H2O2 self-sufficiency

Abstract

The unfavorable factors in tumor microenvironment such as hypoxia and limited H2O2 levels greatly impede the anticancer efficacy of chemotherapy and chemodynamic therapy (CDT). To address these issues and achieve O2/H2O2-sufficient chemo/chemodynamic combination therapy, we synthesized a solid lipid monostearin coated calcium peroxide (CaO2) nanocarrier for the co-delivery of a chemotherapeutic drug doxorubicin (DOX) and a biocompatible Fenton catalyst iron-oleate complex. Specifically, the solid lipid shells of nanoparticles could disintegrate in lipase-overexpressed cancer cells to release iron-oleate and expose CaO2 cores. Afterwards, the uncovered CaO2 responded to the acidic aqueous environment within cancer cells, leading to the release of DOX molecules and generation of H2O2. Based on Fenton reactions, Fe3+ liberated from iron-oleate reacted with H2O2 to produce O2 for hypoxia-relieved chemotherapy, and Fe2+ for the catalytic generation of hydroxyl radical to initiate CDT. Both treatments synergistically contribute to the enhanced antitumor outcomes.