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Chiral Iridium-Based TLD-1433 Analogues: Exploration of Enantiomer-Dependent Behavior in Photodynamic Cancer Therapy.

Wen WangLei WangYangming ZhangYusheng ShiRong ZhangLiyong ChenZhuolin ShiShuai YuanXiaoxi LiChunying DuanXuezhao Li
Published in: Inorganic chemistry (2024)
Metallodrug-based photodynamic therapy (PDT) agents have demonstrated significant superiority against cancers, while their different chirality-induced biological activities remain largely unexplored. In this work, we successfully developed a pair of enantiopure mononuclear Ir(III)-based TLD-1433 analogues, Δ-Ir-3T and Λ - Ir-3T , and their enantiomer-dependent anticancer behaviors were investigated. Photophysical measurements revealed that they display high photostability and chemical stability, strong absorption at 400 nm with high molar extinction coefficients (ε = 5.03 × 10 4 M -1 cm -1 ), and good 1 O 2 relative quantum yields ( Φ Δ ≈ 47%). Δ- and Λ-Ir-3T showed potent efficacy against MCF-7 cancer cells, with a photocytotoxicity index of ≤44 238. This impressive result, to the best of our knowledge, represents the highest value among reported mononuclear Ir(III)-based PDT agents. Remarkably, Λ-Ir-3T tended to be more potent than Δ-Ir-3T when tested against SK-MEL-28, HepG2, and LO2 cells, with consistent results across multiple test repetitions.
Keyphrases
  • photodynamic therapy
  • cancer therapy
  • healthcare
  • fluorescence imaging
  • peripheral blood
  • mass spectrometry
  • signaling pathway
  • cell proliferation
  • high resolution
  • cell death
  • atomic force microscopy
  • quantum dots