Mitochondria-localized dinuclear iridium(III) complexes for two-photon photodynamic therapy
Zanru Tan1, Jiang Feng2, Jiangping Liu3
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, P. R. China. ceschh@mail.sysu.edu.cn.
Dalton Transactions (Cambridge, England : 2003)
|January 29, 2025
Summary
Researchers developed novel dinuclear iridium(III) complexes for two-photon photodynamic therapy (PDT). These complexes target cancer cell mitochondria, generating reactive oxygen species (ROS) for effective cancer treatment with enhanced optical properties.
Area of Science:
- Inorganic Chemistry
- Photochemistry
- Cancer Therapeutics
Background:
- Photodynamic therapy (PDT) is a promising non-invasive cancer treatment due to its selectivity and low toxicity.
- Developing efficient photosensitizers with enhanced optical properties is crucial for advancing PDT.
- Two-photon absorption (2PA) offers improved tissue penetration and spatial resolution for photodynamic applications.
Purpose of the Study:
- To design and synthesize novel dinuclear cyclometalated Iridium(III) complexes for two-photon photodynamic anticancer therapy.
- To investigate the two-photon absorption properties and mitochondrial targeting capabilities of these complexes.
- To evaluate their efficacy as photodynamic anticancer agents under two-photon excitation.
Main Methods:
- Synthesis of a series of dinuclear cyclometalated Iridium(III) complexes.
- Measurement of two-photon absorption (2PA) cross-sections (σ₂).
- Cell viability assays (IC₅₀ determination) and phototoxicity index (PI) evaluation.
- Assessment of reactive oxygen species (ROS) generation and cellular localization (mitochondria targeting).
Main Results:
- The synthesized dinuclear Ir(III) complexes exhibited significant 2PA cross-sections ranging from 66 to 166 GM.
- Complex N-Ir4 demonstrated potent anticancer activity with an IC₅₀ of 2.0 μM and a PI of 24.
- N-Ir4 effectively localized to mitochondria and generated ROS upon two-photon excitation, leading to cell death.
- The dinuclear structure bridged by conjugated rigid planar moieties significantly enhanced optical properties.
Conclusions:
- Dinuclear cyclometalated Ir(III) complexes are effective two-photon photodynamic anticancer agents.
- These complexes exhibit enhanced 2PA properties and specific mitochondrial targeting.
- The study presents a viable strategy for boosting 2PA cross-sections through dinuclear complex design for advanced PDT applications.
