Nanoarchitectonics with metal-organic frameworks and platinum nanozymes with improved oxygen evolution for enhanced sonodynamic/chemo-therapy

Sonodynamic therapy (SDT), which fights against cancers by producing cytotoxic singlet oxygen (1O2) under ultrasound irradiation, has shown great potential in cancer treatment due to its noninvasiveness and deep tissue penetration. However, their practical application suffers from some limitations, such as tumor hypoxia and the inefficient generation of 1O2. To solve these problems, we have prepared the nanoarchitectonics based on metal-organic frameworks (MOFs) containing platinum (Pt) nanozymes with improved oxygen evolution for the enhanced sonodynamic/chemo-therapy effects. As a model of MOF, porous coordination network-224 (PCN-224) nanoparticles with the size of 100 nm have been prepared through coordinating tetrakis (4-carboxyphenyl) porphyrin (TCPP) with Zr(IV) cations during a solvothermal process, and they are then decorated with Pt nanoclusters (∼1.5 nm) by in-situ reduction. After being surface-modified with the phosphatidylcholine and loading DOX, the DOX@PCN-224/Pt nanoplatforms exhibit a good H2O2 catalytic activity, 1O2 generation ability, efficient loading (26.3%) of DOX, and pH-responsive releasing ability. When the DOX@PCN-224/Pt dispersions are intratumorally injected into mice, they can convert the endogenous H2O2 into oxygen for alleviating tumor hypoxia. Moreover, the generated oxygen can further enhance the sensitivity of SDT and tumor cells to chemotherapy by down-regulating the expression of hypoxia-inducible factor α, resulting in the enhanced SDT and chemotherapeutic effect. With these merits, the combination of sonodynamic and chemotherapy of DOX@PCN-224/Pt remarkably inhibits the tumor growth compared to chemotherapy or SDT alone. Therefore, the DOX@PCN-224/Pt nanoplatform serves as an efficient nanoarchitectonics for enhanced sonodynamic/chemo-therapy.