The multiple enzymatic properties of the Au3+-modified metal-organic framework (Au3+-MOFs) have made it a functional catalytic system for antitumor treatment. However, in the face of insufficient catalytic substrates in tumor tissue, it is still impossible to achieve efficient treatment of tumors. Herein, Au3+-MOFs loaded with hyaluronic acid (HA)-modified calcium peroxide nanoparticles (CaO2 NPs) were used to construct a nanozyme (Au3+-MOF/CaO2/HA) for substrate self-supplied and parallel catalytic/calcium-overload-mediated therapy of cancer. Due to the specific targeted ability and retention (EPR) effect of the HA, the built nanozyme can effectively accumulate at the tumor site. Due to the oxidase-like (OXD) activity and peroxidase-like (POD) activity of Au3+-MOFs, superoxide radical anion (O2•-) and hydroxyl radicals (·OH) were cooperatively formed for parallel catalytic therapy (PCT) of cancer. Subsequently, CaO2 NPs were decomposed to Ca2+, H2O2, and O2 in the weak acidic environment of the tumor microenvironment (TME). Thus, self-supplementation of O2 as well as H2O2 was achieved, alleviating the deficiency of Au3+-MOF nanozyme catalytic substrate. In addition, Ca2+ can lead to oxidative stress for tumor calcification and calcium-overload-mediated therapy (COMT) to promote tumor necrosis in vivo. An effective paradigm of tumor PCT/COMT therapy with a self-supplying substrate has been successfully established for considerably enhanced therapeutic efficacy.
Keywords: MOF nanozyme; calcium peroxide; calcium-overload-mediated therapy; oxidase; parallel catalytic therapy; peroxidase.