MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510006, PR China.
Faculty of Chemistry and Biochemistry, Ruhr University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany.
Biomaterials. 2023 Oct;301:122212. doi: 10.1016/j.biomaterials.2023.122212. Epub 2023 Jun 24.
Melanoma represents the most fatal form of skin cancer due to its resistance mechanisms and high capacity for the development of metastases. Among other medicinal techniques, photodynamic therapy is receiving increasing attention. Despite promising results, the application of photodynamic therapy is inherently limited due to interference from melanin, poor tissue penetration of photosensitizers, low loading into drug delivery systems, and a lack of tumor selectivity. To overcome these limitations, herein, the coordination-driven assembly of Ir(III) complex photosensitizers with Fe(III) ions into nanopolymers for combined photodynamic therapy and chemodynamic therapy is reported. While remaining stable under physiological conditions, the nanopolymers dissociated in the tumor microenvironment. Upon exposure to light, the Ir(III) complexes produced singlet oxygen and superoxide anion radicals, inducing cell death by apoptosis and autophagy. The Fe(III) ions were reduced to Fe(II) upon depletion of glutathione and reduction of the GPX4 levels, triggering cell death by ferroptosis. To provide tumor selectivity, the nanopolymers were further camouflaged with exosomes. The generated nanoparticles were found to eradicate a melanoma tumor as well as inhibit the formation of metastases inside a mouse model.
黑色素瘤由于其耐药机制和高转移能力，是最致命的皮肤癌形式。在其他医学技术中，光动力疗法受到越来越多的关注。尽管有很有前景的结果，但由于黑色素的干扰、光敏剂在组织中的穿透性差、在药物传递系统中的载药量低以及缺乏肿瘤选择性，光动力疗法的应用受到固有限制。为了克服这些限制，本研究报告了将 Ir(III) 配合物光敏剂与 Fe(III) 离子配位组装成纳米聚合物，用于联合光动力治疗和化学动力学治疗。纳米聚合物在生理条件下保持稳定，但在肿瘤微环境中解离。暴露于光线下，Ir(III) 配合物产生单线态氧和超氧阴离子自由基，通过细胞凋亡和自噬诱导细胞死亡。谷胱甘肽耗竭和 GPX4 水平降低后，Fe(III) 离子被还原为 Fe(II)，触发铁死亡导致细胞死亡。为了提供肿瘤选择性，纳米聚合物进一步用外泌体伪装。研究发现，生成的纳米颗粒能够消除黑色素瘤肿瘤，并抑制小鼠模型中转移的形成。
