ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1626193
This article is part of the Research TopicPromising Photosensitive Agents for Photodynamic TherapyView all 16 articles
Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis
Provisionally accepted
- 1Tianjin Key Laboratory of Biomedical Material, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College,, Tianjin, China
- 2Tuberculosis Precision Testing Center, Tianjin Haihe Hospital, Tianjin, China
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In previous research, antibacterial photodynamic therapy using lysine-porphyrin conjugate LD4 effectively inactivated methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli; however, it exhibited limited activity against Candida albicans and Mycobacterium tuberculosis. To address this limitation, we developed a synergistic antibacterial strategy by combining LD4 with Cu 2+ or Zn 2+ . Synergy was confirmed via minimum inhibitory concentration and fractional inhibitory concentration index analyses, demonstrating 16-to 64-fold enhanced antibacterial efficacy compared to LD4 alone. Mechanistic studies revealed divergent pathways for LD4 + Cu 2+ and LD4 + Zn 2+ : Zn 2+ increased the reactive oxygen species yield and promoted LD4 uptake by pathogens, while LD4 + Cu 2+ induced oxidative damage to cell walls and membranes in darkness, with light exposure exacerbating structural damage. Cytotoxicity assessments confirmed low toxicity, with >90% survival of normal cells at bactericidal concentrations. Fluorescence and infrared spectroscopy characterized metal-LD4 complexes, showing stabilization through interactions between amino and pyrrolic imino groups of LD4 and metal ions, which promoted non-radiative transitions and fluorescence quenching. Both combinations caused significant bacterial membrane disruption and growth suppression. Notably, cytotoxicity exhibited a biphasic dose-response linked to metal-LD4 complexation-dependent particle size changes. This study elucidated the enhanced antimicrobial mechanisms and safety of LD4-metal ion combinations. The findings resolve the limitations of LD4 while providing a theoretical framework for developing novel therapies against fungal and mycobacterial infections.
Keywords: Antibacterial photodynamic therapy, lysine-conjugated porphyrin compound, Metal ions, Synergistic antibacterial therapy, Candida albicans, Mycobacterium tuberculosis
Received: 10 May 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Wang, Qin, Wen, Chi, Zhang, Wu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tianjun Liu, Tianjin Key Laboratory of Biomedical Material, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College,, Tianjin, China
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