Metal–Organic Framework PCN-224 Integrated with Manganese Dioxide, Platinum Nanoparticles, and Glucose Oxidase for Enhanced Cancer Chemodynamic Therapy

Chemodynamic therapy (CDT) is a highly promising tumor treatment modality that uses the Fenton reaction to convert intracellular hydrogen peroxide (H 2 O 2 ) into cytotoxic hydroxyl groups ( • OH). However, the therapeutic effects of CDT have been restricted by weak acidic pH values, insufficient H 2 O 2 levels, and high glutathione (GSH) concentrations in the tumor microenvironment (TME). In this study, to construct PCN-224-Pt/GOD, porphyrin-based metal–organic framework nanoparticles (PCN-224) were used as the carrier to load Pt and glucose oxidase (GOD). The surface of PCN-224-Pt/GOD was covered with manganese dioxide (MnO 2 ) to fabricate the multifunctional composite nanoparticles PCN-224-Pt/GOD@MnO 2 (P–P/GOD@Mn). P–P/GOD@Mn was used to increase H 2 O 2 levels and to decrease GSH levels for combined CDT and starvation therapy. As a result, we developed P–P/GOD@Mn nanoparticles (diameter, approximately 280 nm) with favorable size and biocompatibility. Under simulated TME conditions, P–P/GOD@Mn nanoparticles could catalyze H 2 O 2 to generate cytotoxic hydroxyl radicals ( • OH), consume glutathione (GSH), and decompose H 2 O 2 to generate oxygen (O 2 ). Cellular toxicity assay results showed that P–P/GOD@Mn killed MCF-7 cells in the TME, with a rate of 77%. The results of tumor-bearing mouse experiments proved that P–P/GOD@Mn nanoparticles could significantly suppress tumor cell growth, which shows the great potential of this entity in CDT and its possibility in bimodal cancer therapy.