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.