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

The unfavorable factors in tumor microenvironment such as hypoxia and limited H 2 O 2 levels greatly impede the anticancer efficacy of chemotherapy and chemodynamic therapy (CDT). To address these issues and achieve O 2 /H 2 O 2 -sufficient chemo/chemodynamic combination therapy, we synthesized a solid lipid monostearin coated calcium peroxide (CaO 2 ) 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 CaO 2 cores. Afterwards, the uncovered CaO 2 responded to the acidic aqueous environment within cancer cells, leading to the release of DOX molecules and generation of H 2 O 2 . Based on Fenton reactions, Fe 3+ liberated from iron-oleate reacted with H 2 O 2 to produce O 2 for hypoxia-relieved chemotherapy, and Fe 2+ for the catalytic generation of hydroxyl radical to initiate CDT. Both treatments synergistically contribute to the enhanced antitumor outcomes.