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抗菌光动力疗法治疗混合感染——从体外到体内的探索。

Antimicrobial photodynamic therapy fighting polymicrobial infections - a journey from in vitro to in vivo.

机构信息

Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center, Vienna, Austria.

出版信息

Photochem Photobiol Sci. 2020 Oct 1;19(10):1332-1343. doi: 10.1039/d0pp00108b. Epub 2020 Sep 30.

DOI:10.1039/d0pp00108b
PMID:32996547
Abstract

Rapidly evolving multidrug resistance renders conventional antimicrobial strategies increasingly inefficient. This urges the exploration of alternative strategies with a lower potential of resistance development to control microbial infections. A promising option is antimicrobial photodynamic therapy (aPDT), especially in the setting of wound infections. In this study its effectiveness was tested as a treatment option for polymicrobially infected wounds in both in vitro and in vivo models. First, aPDT was applied to wound-relevant Gram-positive and Gram-negative bacteria in planktonic culture as the standard in vitro test system and compared different media to show a possible dependency of the therapy on the surrounding environment. In a second step, aPDT was investigated in an in vitro model mimicking the wound bed conditions using fibrin-coated culture plates. Finally, we tested aPDT in vivo in a polymicrobial infected wound healing model in immunocompromised BALB/c mice. In vitro, it was shown that the bactericidal effectiveness of aPDT was strongly dependent on the surrounding environment of the phototoxic reaction. In vivo, the significant delay in wound healing induced by polymicrobial infection was drastically diminished by a two-times application of aPDT using 100 μM methylene blue (generally regarded as safe for topical application on human skin) and 24 J cm pulsed red LED light. Our experiments suggest that aPDT is capable of significantly improving wound healing also in complicated polymicrobially infected wound situations.

摘要

快速出现的多药耐药性使得传统的抗菌策略效率越来越低。这促使人们探索开发替代性策略,以降低耐药性发展的潜力,从而控制微生物感染。一种很有前途的选择是抗菌光动力疗法(aPDT),特别是在伤口感染的情况下。在这项研究中,它的有效性作为一种治疗方案在体外和体内模型中对多微生物感染的伤口进行了测试。首先,将 aPDT 应用于浮游培养中的与伤口相关的革兰氏阳性和革兰氏阴性细菌,作为标准的体外测试系统,并比较了不同的培养基,以显示该疗法可能依赖于周围环境。在第二步中,使用纤维蛋白涂层培养板模拟伤口床条件,在体外模型中研究了 aPDT。最后,我们在免疫功能低下的 BALB/c 小鼠的多微生物感染伤口愈合模型中进行了体内 aPDT 测试。在体外,研究表明,光毒性反应的周围环境强烈影响 aPDT 的杀菌效果。在体内,多微生物感染引起的伤口愈合延迟通过两次应用 aPDT 得到显著改善,使用 100μM 亚甲蓝(通常被认为可安全用于人类皮肤的局部应用)和 24 J cm 脉冲红光,显著减少了延迟。我们的实验表明,aPDT 能够显著改善复杂多微生物感染伤口情况下的伤口愈合。

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