Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
School of Future Technology, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
ACS Appl Bio Mater. 2023 Sep 18;6(9):3376-3386. doi: 10.1021/acsabm.2c01090. Epub 2023 Mar 13.
Recently, photodynamic therapy (PDT) based on the generation of cytotoxic reactive oxygen species (ROS) has drawn great attention in tumor treatment. However, the hypoxia tumor microenvironment (TME) inhibits the generation efficacy of ROS, and the high glutathione (GSH) level in TME could neutralize the generated ROS, both of which strongly reduce the therapeutic efficiency of PDT. In this work, we first constructed the porphyrinic metal-organic framework PCN-224. Then Au nanoparticles were decorated on the PCN-224 to obtain the PCN-224@Au. The decorated Au nanoparticles could not only produce O through the decomposition of HO in tumor sites for enhancing the generation of O in PDT but also deplete glutathione through the strong interactions between Au and sulfhydryl groups on glutathione to weaken the antioxidant ability of tumor cells, thus amplifying the O damage to cancer cells. The and experiments totally exhibited that the as-prepared PCN-224@Au nanoreactor can be used as an oxidative stress amplifier for enhanced PDT, which provides a promising candidate to conquer the limitation of intratumor hypoxia and high GSH level on PDT of cancer.
近年来，基于生成细胞毒性活性氧（ROS）的光动力疗法（PDT）在肿瘤治疗中受到了极大关注。然而，肿瘤微环境（TME）中的缺氧会抑制 ROS 的生成效果，TME 中高浓度的谷胱甘肽（GSH）也可以中和生成的 ROS，这两者都大大降低了 PDT 的治疗效率。在这项工作中，我们首先构建了卟啉金属-有机骨架 PCN-224。然后在 PCN-224 上修饰了金纳米粒子，得到了 PCN-224@Au。修饰的金纳米粒子不仅可以通过肿瘤部位 HO 的分解产生 O，从而增强 PDT 中 O 的生成，还可以通过 Au 与 GSH 上巯基之间的强烈相互作用消耗 GSH，从而削弱肿瘤细胞的抗氧化能力，从而放大 O 对癌细胞的损伤。体外和体内实验都表明，所制备的 PCN-224@Au 纳米反应器可用作增强 PDT 的氧化应激放大器，为克服肿瘤内缺氧和高 GSH 水平对 PDT 的限制提供了有前途的候选物。
