卡巴唑修饰的手性Ir(III)配合物用于光动力肿瘤治疗:手性驱动的生物活性和焦亡活化。

IF 4.7 2区 化学 Q1 CHEMISTRY, INORGANIC & NUCLEAR
Siyi Tao, Shuhan Zhao, Kuang Xu, Jie Peng, Yu Chen, Lingting Guan, Manchang Kou, Xiaoliang Tang* and Jiaxi Ru*, 
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引用次数: 0

摘要

磷光金属配合物作为一种优良的光治疗剂,在癌症治疗中显示出巨大的潜力。然而,它们独特的手性的生物学意义在很大程度上仍未被探索。本文设计并合成了一对咔唑修饰的手性Ir(III)配合物(Δ-Ir-Car和Λ-Ir-Car),作为具有不同生物活性的高效光敏剂(ps)。在Ir(III)配合物中加入两个咔唑基团显著提高了这两个对映体的单线态氧量子产率。这两种对映体在紫外可见吸收、磷光发射、寿命和量子产率等方面表现出几乎相同的物理化学性质,但在生物性能方面表现出显著差异。值得注意的是,与Λ-counterpart相比,Δ-Ir-Car具有更好的细胞摄取、活性氧(ROS)生成能力和肿瘤细胞杀伤效率。重要的是,这两种复合物都诱导焦亡,这是一种促炎细胞死亡途径,具有克服细胞凋亡抵抗和激活抗肿瘤免疫反应的巨大潜力。该研究强调了手性在决定金属基光敏剂生物学结果中的关键作用,并为开发具有增强光动力治疗效果的手性金属药物提供了有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Carbazole-Modified Chiral Ir(III) Complexes for Photodynamic Tumor Therapy: Chirality-Driven Bioactivity and Pyroptosis Activation

Carbazole-Modified Chiral Ir(III) Complexes for Photodynamic Tumor Therapy: Chirality-Driven Bioactivity and Pyroptosis Activation

Phosphorescent metal complexes, as excellent phototheranostic agents, have demonstrated substantial potential in cancer therapy. However, the biological implications of their distinct chirality remain largely unexplored. Herein, we designed and synthesized a pair of carbazole-modified chiral Ir(III) complexes (Δ-Ir-Car and Λ-Ir-Car) as highly potent photosensitizers (PSs) with distinct bioactivities. The incorporation of two carbazole moieties into the Ir(III) complex significantly enhances the singlet oxygen quantum yields for both enantiomers. While displaying nearly identical physicochemical properties in UV–vis absorption, phosphorescence emission, lifetime, and quantum yield, the two enantiomers exhibit remarkable differences in biological performance. Notably, Δ-Ir-Car demonstrates superior cellular uptake, reactive oxygen species (ROS) generation capability, and tumor cell-killing efficiency compared to its Λ-counterpart. Importantly, both complexes induce pyroptosis, a pro-inflammatory cell death pathway, which holds significant potential for overcoming apoptosis resistance and activating antitumor immune responses. This study highlights the critical role of chirality in determining the biological outcomes of metal-based photosensitizers and provides valuable insights for developing chiral metallodrugs with enhanced photodynamic therapeutic efficacy.

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来源期刊
Inorganic Chemistry
Inorganic Chemistry 化学-无机化学与核化学
CiteScore
7.60
自引率
13.00%
发文量
1960
审稿时长
1.9 months
期刊介绍: Inorganic Chemistry publishes fundamental studies in all phases of inorganic chemistry. Coverage includes experimental and theoretical reports on quantitative studies of structure and thermodynamics, kinetics, mechanisms of inorganic reactions, bioinorganic chemistry, and relevant aspects of organometallic chemistry, solid-state phenomena, and chemical bonding theory. Emphasis is placed on the synthesis, structure, thermodynamics, reactivity, spectroscopy, and bonding properties of significant new and known compounds.
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