A photoactivated Ir(III) complex targets cancer stem cells and induces secretion of damage-associated molecular patterns in melanoma cells characteristic of immunogenic cell death,Inorganic Chemistry Frontiers

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A photoactivated Ir(III) complex targets cancer stem cells and induces secretion of damage-associated molecular patterns in melanoma cells characteristic of immunogenic cell death
Inorganic Chemistry Frontiers ( IF 6.1 ) Pub Date : 2021-09-06 , DOI: 10.1039/d1qi00856k
Gloria Vigueras ₁ , Lenka Markova ₂ , Vojtech Novohradsky ₂ , Alicia Marco ₁ , Natalia Cutillas ₁ , Hana Kostrhunova ₂ , Jana Kasparkova ₂ , José Ruiz ₁ , Viktor Brabec ₂

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Several anticancer chemotherapies, while eliminating the bulk of tumor cells, often fail, as they do not obliterate a small fraction of malignant cancer stem cells (CSCs). Thus, developing chemotherapeutics capable of targeting and abrogating CSCs, including inducing immunogenic cell death in CSCs, is essential for developing new anticancer drugs. Herein, we report octahedral Ir(III) complexes based on a benzimidazole backbone containing NH groups. The complexes exhibit low toxicity in the dark against human skin melanoma cells and high phototoxicity with blue light irradiation under both normoxic and hypoxic conditions. Additionally, complex 4 induces secretion of damage-associated molecular patterns characteristic of immunogenic cell death (ICD) in melanoma cells when the cells are irradiated with blue light. The results also suggest that the mechanism of the ICD induced by this complex may involve oxidative damage of intracellular targets by photoinduced ROS generation. This property of 4 may allow targeting the photochemotherapy based on 4 selectively to the tumor.

中文翻译：

光活化的 Ir(III) 复合物靶向癌症干细胞并诱导黑色素瘤细胞中损伤相关分子模式的分泌，其特征是免疫原性细胞死亡

几种抗癌化学疗法在消除大部分肿瘤细胞的同时，往往会失败，因为它们不会消除一小部分恶性癌症干细胞 (CSC)。因此，开发能够靶向和消除 CSCs 的化学疗法，包括诱导 CSCs 中的免疫原性细胞死亡，对于开发新的抗癌药物至关重要。在此，我们报告了基于含有 NH 基团的苯并咪唑骨架的八面体 Ir( III ) 配合物。该复合物在黑暗中对人皮肤黑色素瘤细胞表现出低毒性，在常氧和缺氧条件下对蓝光照射具有高光毒性。此外，复杂的4当用蓝光照射黑色素瘤细胞时，诱导损伤相关分子模式的分泌，这些分子模式是黑色素瘤细胞中免疫原性细胞死亡 (ICD) 的特征。结果还表明，该复合物诱导 ICD 的机制可能涉及光诱导 ROS 产生对细胞内靶标的氧化损伤。4 的这种特性可以允许基于4的光化学疗法选择性地靶向肿瘤。

更新日期：2021-09-13

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