Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering , Southwest Jiaotong University , Chengdu 610031 , Sichuan , P. R. China.
School of Life Science and Engineering , Southwest Jiaotong University , Chengdu 610031 , P. R. China.
ACS Appl Mater Interfaces. 2019 Aug 21;11(33):29579-29592. doi: 10.1021/acsami.9b09671. Epub 2019 Aug 8.
Tumor hypoxia and the short half-life of reactive oxygen species (ROS) with small diffusion distance have greatly limited the therapeutic effect of photodynamic therapy (PDT). Here, a multifunctional nanoplatform is developed to enhance the PDT effect through increasing the oxygen concentration in tumor cells by the Fenton reaction and reducing the distance between the ROS and the target site by mitochondrial targeting. FeO@Dex-TPP nanoparticles are first prepared by coprecipitation in the presence of triphenylphosphine (TPP)-grafted dextran (Dex-TPP) and Fe/Fe, which have a magnetic resonance imaging effect. Next, the photosensitizers of protoporphyrin IX (PpIX) and glutathione-responsive mPEG-ss-COOH are grafted on FeO@Dex-TPP to form FeO@Dex/TPP/PpIX/ss-mPEG nanoparticles. After the nanoparticles are internalized, part of FeO are decomposed into Fe/Fe in the acidic lysosome and then Fe/Fe diffused into the cytoplasm, and subsequently, Fe reacted with the overproduced HO to produce O and OH. The undecomposed nanoparticles enter the cytoplasm by photoinduced internalization and targeted to the mitochondria, leading to ROS direct generation around the mitochondria. Simultaneously, the produced O by the Fenton reaction can serve as a raw material for PDT to continuously exert PDT effect. As a result, the Fenton reaction-assisted PDT can significantly improve the therapeutic efficacy of tumors.
肿瘤缺氧和活性氧（ROS）的半衰期短且扩散距离小，极大地限制了光动力疗法（PDT）的治疗效果。在这里，开发了一种多功能纳米平台，通过芬顿反应增加肿瘤细胞中的氧浓度，并通过靶向线粒体减少 ROS 与靶位之间的距离，从而增强 PDT 效果。首先，在存在三苯基膦（TPP）接枝葡聚糖（Dex-TPP）和 Fe/Fe 的情况下，通过共沉淀制备了具有磁共振成像效果的 FeO@Dex-TPP 纳米粒子。接下来，将原卟啉 IX（PpIX）和谷胱甘肽响应性 mPEG-ss-COOH 的光敏剂接枝到 FeO@Dex-TPP 上，形成 FeO@Dex/TPP/PpIX/ss-mPEG 纳米粒子。纳米粒子被内化后，部分 FeO 在酸性溶酶体中分解为 Fe/Fe，然后 Fe/Fe 扩散到细胞质中，随后，Fe 与过量产生的 HO 反应生成 O 和 OH。未分解的纳米粒子通过光诱导内化进入细胞质，并靶向线粒体，导致线粒体周围直接产生 ROS。同时，芬顿反应产生的 O 可以作为 PDT 的原料，持续发挥 PDT 作用。结果，芬顿反应辅助 PDT 可以显著提高肿瘤的治疗效果。
