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Monosubstituted tricationic Zn(II) phthalocyanine enhances antimicrobial photodynamic inactivation (aPDI) of methicillin-resistant Staphylococcus aureus (MRSA) and cytotoxicity evaluation for topical applications: in vitro and in vivo study.
Emerging Microbes & Infections ( IF 13.2 ) Pub Date : 2020-07-14 , DOI: 10.1080/22221751.2020.1790305
Priyanga Dharmaratne 1 , Baiyan Wang 1 , Roy C H Wong 2 , Ben C L Chan 3 , Kit-Man Lau 3 , Mei-Rong Ke 2 , Clara B S Lau 3 , Dennis K P Ng 2 , Kwok-Pui Fung 1, 3, 4 , Margaret Ip 5, 6
Affiliation  

ABSTRACT

Antimicrobial photodynamic therapy (aPDT) is an innovative approach to combat multi-drug resistant bacteria. It is known that cationic Zn(II) phthalocyanines (ZnPc) are effective in mediating aPDT against methicillin-resistant Staphylococcus aureus (MRSA). Here we used ZnPc-based photosensitizer named ZnPcE previously reported by our research group to evaluate its aPDT efficacy against broad spectrum of clinically relevant MRSAs. Remarkably, in vitro anti-MRSA activity was achieved using near-infrared (NIR, >610 nm) light with minimal bactericidal concentrations ranging <0.019–0.156 µM against the panel of MRSAs. ZnPcE was not only significantly (p < .05) more potent than methylene blue, which is a clinically approved photosensitizer but also demonstrated low cytotoxicity against human fibroblasts cell line (Hs-27) and human immortalized keratinocytes cell line (HaCaT). The toxicity was further evaluated on human 3-D skin constructs and found ZnPcE did not manifest in vivo skin irritation at ≤7.8 µM concentration. In the murine MRSA wound model, ZnPcE with PDT group demonstrated > 4 log10 CFU reduction and the value is significantly higher (p < .05) than all test groups except positive control. To conclude, results of present study provide a scientific basis for future clinical evaluation of ZnPcE-PDT on MRSA wound infection.



中文翻译:

单取代三阳离子Zn(II)酞菁可增强耐甲氧西林的金黄色葡萄球菌(MRSA)的抗菌光动力学灭活(aPDI)以及用于局部应用的细胞毒性评估:体外和体内研究。

摘要

抗菌素光动力疗法(aPDT)是一种对抗多药耐药细菌的创新方法。众所周知,阳离子Zn(II)酞菁(ZnPc)可有效介导aPDT抵抗耐甲氧西林的金黄色葡萄球菌(MRSA)。在这里,我们使用了我们的研究小组先前报告的基于ZnPc的光敏剂ZnPcE来评估其针对广泛临床相关MRSA的aPDT功效。值得注意的是,使用近红外(NIR,> 610 nm)光对MRSA的最小杀菌浓度范围在<0.019-0.156 µM,可实现体外抗MRSA活性。ZnPcE不仅显著(p <.05)比亚甲蓝更强效,亚甲蓝是一种临床认可的光敏剂,但对人成纤维细胞细胞系(Hs-27)和人类永生化角质形成细胞系(HaCaT)的细胞毒性较低。进一步评估了对人3-D皮肤构建物的毒性,发现ZnPcE在≤7.8µM浓度下未表现出体内皮肤刺激性。在鼠MRSA伤口模型中,PDT组的ZnPcE表现出降低了> 4 log 10 CFU,并且该值显着高于 除阳性对照组以外的所有测试组(p <.05)。总而言之,本研究结果为ZnPcE-PDT对MRSA伤口感染的未来临床评估提供了科学依据。

更新日期:2020-07-14
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