Mitochondria-Targeting Upconversion Nanoparticles@MOF for Multiple-Enhanced Photodynamic Therapy in Hypoxic Tumor

The effect of photodynamic therapy (PDT) is severelylimited bytumor hypoxia and the short half-life of reactive oxygen species (ROS).Herein, we constructed a near-infrared (NIR) light-regulated PDT nanoplatform(TPP-UCNPs@MOF-Pt) consisting of an upconversion nanoparticle (UCNP)core and porphyrin-based metal-organic framework (MOF) shellwith platinum nanoparticles (PtNPs) and a mitochondria-targeting triphenylphosphine(TPP) group on the surface. TPP-UCNPs@MOF-Pt could effectively relievethe tumor hypoxia by converting intracellular H2O2 to oxygen (O-2) and elevated the ROS level to enhancePDT efficacy under NIR light irradiation. In addition, the mitochondria-targetingTPP-UCNPs@MOF-Pt was localized on the mitochondria, leading to severedepolarization of the mitochondrial membrane and activation of theapoptotic pathway, further amplifying the therapeutic efficacy. In vitro and in vivo experiments demonstratedthat the greatly enhanced photodynamic therapeutic efficacy of TPP-UCNPs@MOF-Ptwas achieved by combining relief of tumor hypoxia with mitochondrialtargeting and NIR activation. This study provides a promising strategyfor construction of an MOF-based multifunctional nanoplatform to addressthe current limitations of PDT treatment for hypoxic tumors.