Exploring a Mitochondria Targeting, Dinuclear Cyclometalated Iridium (III) Complex for Image-Guided Photodynamic Therapy in Triple-Negative Breast Cancer Cells

被引:10
作者
Neelambaran, Nishna [1 ,2 ]
Shamjith, Shanmughan [1 ,2 ]
Murali, Vishnu Priya [1 ,2 ]
Maiti, Kaustabh Kumar [1 ,2 ]
Joseph, Joshy [1 ,2 ]
机构
[1] Natl Inst Interdisciplinary Sci & Technol CSIR NII, Chem Sci & Technol Div CSTD, Thiruvananthapuram 695019, Kerala, India
[2] Acad Sci & Innovat Res AcSIR, Ghaziabad 201002, India
关键词
dinuclear iridium complex; reactive oxygen species (ROS); photosensitizers (PSs); photodynamic therapy (PDT); targeted therapy; apoptosis; METAL-COMPLEXES; LIVE CELL; PHOTOSENSITIZERS; METASTASIS; LYSOSOME; PROBES; AGENTS; DYES;
D O I
10.1021/acsabm.3c00883
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Photodynamic therapy (PDT) has emerged as an efficient and noninvasive treatment approach utilizing laser-triggered photosensitizers for combating cancer. Within this rapidly advancing field, iridium-based photosensitizers with their dual functionality as both imaging probes and PDT agents exhibit a potential for precise and targeted therapeutic interventions. However, most reported classes of Ir(III)-based photosensitizers comprise mononuclear iridium(III), with very few examples of dinuclear systems. Exploring the full potential of iridium-based dinuclear systems for PDT applications remains a challenge. Herein, we report a dinuclear Ir(III) complex (IRDI) along with a structurally similar monomer complex (IRMO) having 2-(2,4-difluorophenyl)pyridine and 4 '-methyl-2,2 '-bipyridine ligands. The comparative investigation of the mononuclear and dinuclear Ir(III) complexes showed similar absorption profiles, but the dinuclear derivative IRDI exhibited a higher photoluminescence quantum yield (Phi(p)) of 0.70 compared to that of IRMO (Phi(p) = 0.47). Further, IRDI showed a higher singlet oxygen generation quantum yield (Phi(s)) of 0.49 compared to IRMO (Phi(s) = 0.28), signifying the enhanced potential of the dinuclear derivative for image-guided photodynamic therapy. In vitro assessments indicate that IRDI shows efficient cellular uptake and significant photocytotoxicity in the triple-negative breast cancer cell line MDA-MB-231. In addition, the presence of a dual positive charge on the dinuclear system facilitates the inherent mitochondria-targeting ability without the need for a specific targeting group. Subcellular singlet oxygen generation by IRDI was confirmed using Si-DMA, and light-activated cellular apoptosis via ROS-mediated PDT was verified through various live-dead assays performed in the presence and absence of the singlet oxygen scavenger NaN3. Further, the mechanism of cell death was elucidated by an annexin V-FITC/PI flow cytometric assay and by investigating the cytochrome c release from mitochondria using Western blot analysis. Thus, the dinuclear complex designed to enhance spin-orbit coupling with minimal excitonic coupling represents a promising strategy for efficient image-guided PDT using iridium complexes.
引用
收藏
页码:5776 / 5788
页数:13
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