Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial Infections
To address the clinical challenges posed by symbiotic drug-resistant bacterial infections and tumor microenvironments, this study designed and synthesized novel carbazole/benzindole-based photosensitizers <b>A1</b>–<b>A4</b>, systematically evaluating their antitumor and anti...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/12/2560 |
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| author | Zihao Wang Xiao Liu Yifan Ma Jiaxin Zheng Ke Xu Yingxue Chang Zhaoyan Ye Yong Ling Lei Wang |
| author_facet | Zihao Wang Xiao Liu Yifan Ma Jiaxin Zheng Ke Xu Yingxue Chang Zhaoyan Ye Yong Ling Lei Wang |
| author_sort | Zihao Wang |
| collection | DOAJ |
| description | To address the clinical challenges posed by symbiotic drug-resistant bacterial infections and tumor microenvironments, this study designed and synthesized novel carbazole/benzindole-based photosensitizers <b>A1</b>–<b>A4</b>, systematically evaluating their antitumor and antibacterial therapeutic potential through chemo-photodynamic therapy. Especially, compound <b>A4</b> demonstrated potent Type I/II reactive oxygen species (ROS) generation capabilities. In vitro experiments revealed that <b>A4</b> concentration-dependently inhibited HT-29 cells under hypoxic conditions (IC<sub>50</sub> = 0.89 μM) with a prominent photodynamic index (PI > 9.23), and substantially promoted cancer cell programmed death. In antibacterial evaluations, <b>A4</b> achieved the complete eradication of dermal MRSA infections within 7 days through ROS-mediated membrane disruption under illumination. In the HT-29 xenograft model, the PDT–chemotherapy synergy strategy achieved a tumor suppression rate of 96%. This work establishes an innovative strategy for the combinatorial management of multidrug-resistant infections and solid tumors. |
| format | Article |
| id | doaj-art-c87b95c2643a484faec059151346151a |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-c87b95c2643a484faec059151346151a2025-08-20T02:20:59ZengMDPI AGMolecules1420-30492025-06-013012256010.3390/molecules30122560Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial InfectionsZihao Wang0Xiao Liu1Yifan Ma2Jiaxin Zheng3Ke Xu4Yingxue Chang5Zhaoyan Ye6Yong Ling7Lei Wang8Department of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Nantong University, Nantong 226001, ChinaTo address the clinical challenges posed by symbiotic drug-resistant bacterial infections and tumor microenvironments, this study designed and synthesized novel carbazole/benzindole-based photosensitizers <b>A1</b>–<b>A4</b>, systematically evaluating their antitumor and antibacterial therapeutic potential through chemo-photodynamic therapy. Especially, compound <b>A4</b> demonstrated potent Type I/II reactive oxygen species (ROS) generation capabilities. In vitro experiments revealed that <b>A4</b> concentration-dependently inhibited HT-29 cells under hypoxic conditions (IC<sub>50</sub> = 0.89 μM) with a prominent photodynamic index (PI > 9.23), and substantially promoted cancer cell programmed death. In antibacterial evaluations, <b>A4</b> achieved the complete eradication of dermal MRSA infections within 7 days through ROS-mediated membrane disruption under illumination. In the HT-29 xenograft model, the PDT–chemotherapy synergy strategy achieved a tumor suppression rate of 96%. This work establishes an innovative strategy for the combinatorial management of multidrug-resistant infections and solid tumors.https://www.mdpi.com/1420-3049/30/12/2560photodynamic therapy (PDT)drug-resistant bacterial infectionMRSAreactive oxygen species (ROS)tumor microenvironment |
| spellingShingle | Zihao Wang Xiao Liu Yifan Ma Jiaxin Zheng Ke Xu Yingxue Chang Zhaoyan Ye Yong Ling Lei Wang Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial Infections Molecules photodynamic therapy (PDT) drug-resistant bacterial infection MRSA reactive oxygen species (ROS) tumor microenvironment |
| title | Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial Infections |
| title_full | Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial Infections |
| title_fullStr | Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial Infections |
| title_full_unstemmed | Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial Infections |
| title_short | Novel Type I/II Carbazole/Benzindole Photosensitizers Achieve Chemo-Photodynamic Synergistic Therapy for Suppressing Solid Tumors and Drug-Resistant Bacterial Infections |
| title_sort | novel type i ii carbazole benzindole photosensitizers achieve chemo photodynamic synergistic therapy for suppressing solid tumors and drug resistant bacterial infections |
| topic | photodynamic therapy (PDT) drug-resistant bacterial infection MRSA reactive oxygen species (ROS) tumor microenvironment |
| url | https://www.mdpi.com/1420-3049/30/12/2560 |
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