将光敏剂整合到缺氧激活前药中，为协同癌症治疗提供了一种有前途的策略。
A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug.
机构信息
National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou, 350108, China; Key Laboratory of Molecule Synthesis and Function Discovery, Fujian Province University, College of Chemistry, Fuzhou University, Fuzhou, 350108, China; State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
出版信息
Eur J Med Chem. 2022 Dec 5;243:114749. doi: 10.1016/j.ejmech.2022.114749. Epub 2022 Sep 9.
Herein, we fabricate a multifunctional molecular prodrug BAC where the chemotherapeutical agent camptothecin (CPT) is linked with a boron dipyrromethene (BODIPY)-based photosensitizer by an azobenzene chain which is sensitive to over-expressed azoreductase in hypoxic tumor cells. This prodrug was further loaded into biodegradable monomethoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) to improve its solubility and tumor accumulation. The formed BAC nanoparticles (BAC NPs) can destroy aerobic tumor cells with relatively short distance from blood vessels by photodynamic therapy (PDT) under illumination. The PDT action inevitably leads to consumption of O, and subsequently acute hypoxia which can induce cleavage of azobenzene linkage to boost release of CPT killing the other hypoxic interior tumor cells survived from PDT. Both in vitro and in vivo studies have verified that BAC NPs possess remarkable antitumor activity by a synergistic action of PDT and chemotherapy.
在这里，我们制备了一种多功能分子前药 BAC，其中化疗药物喜树碱（CPT）通过偶氮苯链与基于硼二吡咯甲川（BODIPY）的光敏剂连接，该偶氮苯链对缺氧肿瘤细胞中过表达的芳基还原酶敏感。该前药进一步负载到可生物降解的单甲氧基聚乙二醇-b-聚己内酯（mPEG-b-PCL）中，以提高其溶解度和肿瘤积累。形成的 BAC 纳米颗粒（BAC NPs）可以通过光动力疗法（PDT）在光照下破坏距离血管较近的有氧肿瘤细胞。PDT 作用不可避免地导致 O 的消耗，随后出现急性缺氧，这可以诱导偶氮苯键的断裂，从而促进 CPT 的释放，杀死 PDT 未能杀死的其他缺氧内部肿瘤细胞。体外和体内研究都验证了 BAC NPs 通过 PDT 和化学疗法的协同作用具有显著的抗肿瘤活性。
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