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蓝光激活的5,10,15,20-四(4-溴苯基)卟啉用于光动力根除耐药菌

Blue light-activated 5,10,15,20-tetrakis(4-bromophenyl)porphyrin for photodynamic eradication of drug-resistant .

作者信息

Qin Hongshuang, Niu Huaying, Guo Yanxiang, Wang Xiaoting, Liu Tao, Zhao Chuanqi

机构信息

Department of Biological and Food Engineering, Lyuliang University Lvliang Shanxi 033001 China.

Department of Chemistry and Chemical Engineering, Lyuliang University Lvliang Shanxi 033001 China

出版信息

RSC Adv. 2024 Dec 18;14(53):39779-39786. doi: 10.1039/d4ra07666d. eCollection 2024 Dec 10.

Abstract

Photodynamic therapy (PDT) has emerged as an effective way to deal with drug-resistant bacterial infections. Especially, blue light (BL) mediated PDT (BL-PDT) presents unique advantages in the treatments of skin infection due to the strong light absorption of superficial skin, weak penetration of BL and little damage to deep tissues. However, the photosensitizers used for BL-PDT are very limited, and the ongoing development of novel BL photosensitizers is indispensable. Porphyrins are good sources for developing efficient photosensitizers. Herein, for developing more effective BL photosensitizers, five porphyrin derivatives that can be excited by BL [5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetrakis(4-bromophenyl)porphyrin (TBPP), 5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (TCPP), 5,10,15,20-tetrakis(4-fluorophenyl)porphyrin (TFPP), 5,10,15,20-tetrakis(4-iodophenyl)porphyrin (TIPP)] are subjected to the investigation of PDT against MRSA (methicillin resistant ). The results reveal that TBPP-mediated BL-PDT shows outstanding bactericidal effects. Mechanism studies show that TBPP + BL can induce reactive oxygen species (ROS) up-regulated in MRSA, rupture cell membrane, inhibit ATP (adenosine triphosphate) production and virulence factor expression. Furthermore, TBPP + BL effectively eliminates MRSA form biofilms, inhibits biofilm formation and disintegrates mature biofilms. More importantly, TBPP-PDT significantly accelerate mouse skin wound healing in a biofilm infection model. Our work offers new insights into the development of novel BL photosensitizers.

摘要

光动力疗法(PDT)已成为应对耐药细菌感染的一种有效方法。特别是,蓝光(BL)介导的光动力疗法(BL-PDT)在皮肤感染治疗中具有独特优势,这是由于浅表皮肤对光的强烈吸收、蓝光的弱穿透性以及对深部组织的损伤较小。然而,用于BL-PDT的光敏剂非常有限,因此不断开发新型蓝光光敏剂是必不可少的。卟啉是开发高效光敏剂的良好来源。在此,为了开发更有效的蓝光光敏剂,对五种可被蓝光激发的卟啉衍生物[5,10,15,20-四苯基卟啉(TPP)、5,10,15,20-四(4-溴苯基)卟啉(TBPP)、5,10,15,20-四(4-氯苯基)卟啉(TCPP)、5,10,15,20-四(4-氟苯基)卟啉(TFPP)、5,10,15,20-四(4-碘苯基)卟啉(TIPP)]进行了针对耐甲氧西林金黄色葡萄球菌(MRSA)的光动力疗法研究。结果表明,TBPP介导的BL-PDT具有出色的杀菌效果。机制研究表明,TBPP + BL可诱导MRSA中活性氧(ROS)上调,破坏细胞膜,抑制三磷酸腺苷(ATP)生成和毒力因子表达。此外,TBPP + BL可有效消除生物膜中的MRSA,抑制生物膜形成并分解成熟生物膜。更重要的是,在生物膜感染模型中,TBPP-PDT可显著加速小鼠皮肤伤口愈合。我们的工作为新型蓝光光敏剂的开发提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34c9/11653106/bd2648e66b8f/d4ra07666d-f1.jpg

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