Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy
Photosensitizers with high singlet oxygen (<sup>1</sup>O<sub>2</sub>) generation capacity under near-infrared (NIR) irradiation are essential and challenging for photodynamic therapy (PDT). A simple yet effective molecular design strategy is realized to construct 1 + 1 > 2...
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MDPI AG
2025-06-01
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| author | Ziwei Wang Weijin Wang Qi Wu Dongxia Zhu |
| author_facet | Ziwei Wang Weijin Wang Qi Wu Dongxia Zhu |
| author_sort | Ziwei Wang |
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| description | Photosensitizers with high singlet oxygen (<sup>1</sup>O<sub>2</sub>) generation capacity under near-infrared (NIR) irradiation are essential and challenging for photodynamic therapy (PDT). A simple yet effective molecular design strategy is realized to construct 1 + 1 > 2 photosensitizers with synergistic effects by covalently integrating iridium complexes with cyanine via ether linkages, as well as introducing aldehyde groups to suppress non-radiative decay, named <b>CHO−Ir−Cy</b>. It is demonstrated that <b>CHO−Ir−Cy</b> successfully maintains the NIR absorption and emission originated from cyanine units and high <sup>1</sup>O<sub>2</sub> generation efficiency from the iridium complex part, which gives full play to their respective advantages while compensating for shortcomings. Density functional theory (DFT) calculations reveal that <b>CHO−Ir−Cy</b> exhibits a stronger spin–orbit coupling constant (ξ (S1, T1) = 9.176 cm<sup>−1</sup>) and a reduced energy gap (ΔE = −1.97 eV) between triplet excited states (T<sub>1</sub>) and first singlet excited states (S<sub>1</sub>) compared to parent Ir−Cy or Cy alone, directly correlating with its enhanced <sup>1</sup>O<sub>2</sub> production. Remarkably, <b>CHO−Ir−Cy</b> demonstrates superior cellular internalization in 4T1 murine breast cancer cells, generating substantially elevated <sup>1</sup>O<sub>2</sub> yields compared to individual Ir−Cy/Cy under 808 nm laser irradiation. Such enhanced reactive oxygen species production translates into effective cancer cell ablation while maintaining favorable biocompatibility, significant phototoxicity and negligible dark toxicity. This molecular engineering strategy overcomes the inherent NIR absorption limitation of traditional iridium complexes and ensures their own high <sup>1</sup>O<sub>2</sub> generation ability through dye–metal synergy, establishing a paradigm for designing metal–organic photosensitizers with tailored photophysical properties for precision oncology. |
| format | Article |
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| institution | OA Journals |
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| language | English |
| publishDate | 2025-06-01 |
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| series | Molecules |
| spelling | doaj-art-1759da258beb44848ff0ec4e42d85dae2025-08-20T02:21:14ZengMDPI AGMolecules1420-30492025-06-013012266210.3390/molecules30122662Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer TherapyZiwei Wang0Weijin Wang1Qi Wu2Dongxia Zhu3Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun 130024, ChinaKey Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun 130024, ChinaKey Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun 130024, ChinaKey Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun 130024, ChinaPhotosensitizers with high singlet oxygen (<sup>1</sup>O<sub>2</sub>) generation capacity under near-infrared (NIR) irradiation are essential and challenging for photodynamic therapy (PDT). A simple yet effective molecular design strategy is realized to construct 1 + 1 > 2 photosensitizers with synergistic effects by covalently integrating iridium complexes with cyanine via ether linkages, as well as introducing aldehyde groups to suppress non-radiative decay, named <b>CHO−Ir−Cy</b>. It is demonstrated that <b>CHO−Ir−Cy</b> successfully maintains the NIR absorption and emission originated from cyanine units and high <sup>1</sup>O<sub>2</sub> generation efficiency from the iridium complex part, which gives full play to their respective advantages while compensating for shortcomings. Density functional theory (DFT) calculations reveal that <b>CHO−Ir−Cy</b> exhibits a stronger spin–orbit coupling constant (ξ (S1, T1) = 9.176 cm<sup>−1</sup>) and a reduced energy gap (ΔE = −1.97 eV) between triplet excited states (T<sub>1</sub>) and first singlet excited states (S<sub>1</sub>) compared to parent Ir−Cy or Cy alone, directly correlating with its enhanced <sup>1</sup>O<sub>2</sub> production. Remarkably, <b>CHO−Ir−Cy</b> demonstrates superior cellular internalization in 4T1 murine breast cancer cells, generating substantially elevated <sup>1</sup>O<sub>2</sub> yields compared to individual Ir−Cy/Cy under 808 nm laser irradiation. Such enhanced reactive oxygen species production translates into effective cancer cell ablation while maintaining favorable biocompatibility, significant phototoxicity and negligible dark toxicity. This molecular engineering strategy overcomes the inherent NIR absorption limitation of traditional iridium complexes and ensures their own high <sup>1</sup>O<sub>2</sub> generation ability through dye–metal synergy, establishing a paradigm for designing metal–organic photosensitizers with tailored photophysical properties for precision oncology.https://www.mdpi.com/1420-3049/30/12/2662near infraredIr(III) complexcyanine dyephotodynamic therapy |
| spellingShingle | Ziwei Wang Weijin Wang Qi Wu Dongxia Zhu Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy Molecules near infrared Ir(III) complex cyanine dye photodynamic therapy |
| title | Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy |
| title_full | Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy |
| title_fullStr | Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy |
| title_full_unstemmed | Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy |
| title_short | Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy |
| title_sort | constructing 1 1 2 photosensitizers based on nir cyanine iridium iii complexes for enhanced photodynamic cancer therapy |
| topic | near infrared Ir(III) complex cyanine dye photodynamic therapy |
| url | https://www.mdpi.com/1420-3049/30/12/2662 |
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