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 H2O2 levels greatly impede the anticancer efficacy of chemotherapy and chemodynamic therapy (CDT). To address these issues and achieve O-2/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 O-2 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. Statement of significance In this work, a solid lipid coated calcium peroxide (CaO2) nanocarrier was designed to deliver doxorubicin and iron-oleate complex for O-2 /H2O2 -sufficient chemo/chemodynamic cancer therapy. Although CaO2 has been previously used as a O-2-producer for tumor hypoxia relief, the acidic tumor environment enabled limited O-2 production of CaO2. Here, we highlighted the dual functions of the biocompatible Fenton catalyst, iron-oleate, which was able to catalyze the elevated generation of center dot OH for CDT, as well as O-2 to enhance chemotherapy. Besides, the solid lipid monostearin was employed to increase the stability, tumor selectiveness, and biocompatibility of nanoparticles. Both in vitro and in vivo, we confirmed the enhanced anticancer efficacy and satisfactory biosafety of this nanomedicine. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

A solid lipid coated calcium peroxide (CaO2) nanocarrier was synthesized to deliver doxorubicin and iron-oleate complex for O-2 /H2O2 -sufficient chemo/chemodynamic cancer therapy. The biocompatible Fenton catalyst, iron-oleate, played dual functions in catalyzing generation of center dot OH for CDT and O-2 for enhanced chemotherapy, while the solid lipid monostearin increased stability and tumor selectiveness of nanoparticles. Both in vitro and in vivo experiments confirmed the enhanced anticancer efficacy and biosafety of this nanomedicine.