Metal–Organic Framework PCN-224 Integrated with Manganese Dioxide, Platinum Nanoparticles, and Glucose Oxidase for Enhanced Cancer Chemodynamic Therapy
Longbao Zhu, Ting Gui, Ping Song, Wanzhen Li, Jun Wang, Chengrui Hu, Yuanchen Sun, Fei Ge, Weiwei Zhang
Abstract
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.