A mitochondria-localized iridium(III) photosensitizer for two-photon photodynamic immunotherapy against melanoma,Chemical Science

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A mitochondria-localized iridium(III) photosensitizer for two-photon photodynamic immunotherapy against melanoma
Chemical Science ( IF 7.6 ) Pub Date : 2023-01-12 , DOI: 10.1039/d2sc06675k
Lili Wang _{1,

2} , Johannes Karges ₃ , Fangmian Wei ₁ , Lina Xie ₁ , Zhuoli Chen ₁ , Gilles Gasser ₄ , Liangnian Ji ₁ , Hui Chao _{1,

5}

Affiliation

Conventional photodynamic therapy mainly causes a therapeutic effect on the primary tumor through the localized generation of reactive oxygen species, while metastatic tumors remain poorly affected. Complementary immunotherapy is effective in eliminating small, non-localized tumors distributed across multiple organs. Here, we report the Ir(III) complex Ir-pbt-Bpa as a highly potent immunogenic cell death inducing photosensitizer for two-photon photodynamic immunotherapy against melanoma. Ir-pbt-Bpa can produce singlet oxygen and superoxide anion radicals upon light irradiation, causing cell death by a combination of ferroptosis and immunogenic cell death. In a mouse model with two physically separated melanoma tumors, although only one of the primary tumors was irradiated, a strong tumor reduction of both tumors was observed. Upon irradiation, Ir-pbt-Bpa not only induced the immune response of CD8⁺ T cells and the depletion of regulatory T cells, but also caused an increase in the number of the effector memory T cells to achieve long-term anti-tumor immunity.

中文翻译：

用于针对黑色素瘤的双光子光动力免疫疗法的线粒体定位铱（III）光敏剂

传统的光动力疗法主要通过局部产生活性氧对原发肿瘤产生治疗作用，而对转移肿瘤的影响较小。补充免疫疗法可有效消除分布在多个器官的小型非局部肿瘤。在这里，我们报道了 Ir( III ) 复合物 Ir-pbt-Bpa 作为一种高效的免疫原性细胞死亡诱导光敏剂，用于针对黑色素瘤的双光子光动力免疫疗法。 Ir-pbt-Bpa 在光照射下可产生单线态氧和超氧阴离子自由基，通过铁死亡和免疫原性细胞死亡的组合导致细胞死亡。在具有两个物理上分离的黑色素瘤的小鼠模型中，尽管仅照射了其中一个原发性肿瘤，但观察到两个肿瘤的肿瘤明显减少。照射后，Ir-pbt-Bpa不仅诱导CD8 ⁺ T细胞的免疫反应和调节性T细胞的耗竭，而且引起效应记忆T细胞数量的增加，以实现长期的抗肿瘤免疫。

更新日期：2023-01-12

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