Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.
ACS Appl Mater Interfaces. 2023 Aug 2;15(30):35884-35894. doi: 10.1021/acsami.3c05447. Epub 2023 Jul 24.
The effect of photodynamic therapy (PDT) is severely limited by tumor 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) shell with platinum nanoparticles (PtNPs) and a mitochondria-targeting triphenylphosphine (TPP) group on the surface. TPP-UCNPs@MOF-Pt could effectively relieve the tumor hypoxia by converting intracellular HO to oxygen (O) and elevated the ROS level to enhance PDT efficacy under NIR light irradiation. In addition, the mitochondria-targeting TPP-UCNPs@MOF-Pt was localized on the mitochondria, leading to severe depolarization of the mitochondrial membrane and activation of the apoptotic pathway, further amplifying the therapeutic efficacy. and experiments demonstrated that the greatly enhanced photodynamic therapeutic efficacy of TPP-UCNPs@MOF-Pt was achieved by combining relief of tumor hypoxia with mitochondrial targeting and NIR activation. This study provides a promising strategy for construction of an MOF-based multifunctional nanoplatform to address the current limitations of PDT treatment for hypoxic tumors.
光动力疗法（PDT）的效果受到肿瘤缺氧和活性氧（ROS）半衰期短的严重限制。在此，我们构建了一种近红外（NIR）光调控的 PDT 纳米平台（TPP-UCNPs@MOF-Pt），由上转换纳米颗粒（UCNP）核和基于卟啉的金属-有机骨架（MOF）壳组成，表面带有铂纳米颗粒（PtNPs）和线粒体靶向三苯基膦（TPP）基团。TPP-UCNPs@MOF-Pt 可以有效地将细胞内的 HO 转化为氧气（O），从而缓解肿瘤缺氧，并在 NIR 光照射下提高 ROS 水平，增强 PDT 疗效。此外，线粒体靶向的 TPP-UCNPs@MOF-Pt 定位于线粒体，导致线粒体膜严重去极化和凋亡途径的激活，进一步放大治疗效果。体内和体外实验证明，通过结合缓解肿瘤缺氧、线粒体靶向和 NIR 激活，TPP-UCNPs@MOF-Pt 大大增强了光动力治疗效果。这项研究为构建基于 MOF 的多功能纳米平台提供了一种有前途的策略，以解决缺氧肿瘤 PDT 治疗的当前限制。
