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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Main Authors: Zihao Wang, Xiao Liu, Yifan Ma, Jiaxin Zheng, Ke Xu, Yingxue Chang, Zhaoyan Ye, Yong Ling, Lei Wang
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/12/2560
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Summary: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.
ISSN:1420-3049