Antimicrobial photodynamic therapy fighting polymicrobial infections - a journey fromin vitrotoin vivo
Antimicrobial photodynamic therapy fighting polymicrobial infections - a journey fromin vitrotoin vivo
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DOI：
10.1039/d0pp00108b
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发表时间：
2020-10-01
影响因子：
3.1
通讯作者：
Dungel, Peter
中科院分区：
文献类型：
--
作者：
Karner, Lisa;Drechsler, Susanne;Dungel, Peter
快速发展的多药耐药性使得传统的抗微生物策略越来越低效。这促使探索具有较低耐药性发展潜力的替代策略来控制微生物感染。抗菌光动力疗法（aPDT）是一个很有前途的选择，特别是在伤口感染的情况下。在这项研究中，它作为一种治疗多微生物感染伤口的选择，在体外和体内模型进行了测试。首先，将aPDT应用于浮游培养中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检验系统，并比较不同培养基，以显示治疗对周围环境的可能依赖性。第二步，利用纤维蛋白包被培养板在模拟创面条件的体外模型中研究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检测aPDTin。体外实验表明，aPDT的杀菌效果强烈依赖于光毒性反应的周围环境。在体内，使用100 μ M亚甲基蓝（通常被认为对人体皮肤局部应用是安全的）和24 J cm（-2）脉冲红色LED灯两次应用aPDT，可显著减少由多微生物感染引起的伤口愈合延迟。我们的实验表明，aPDT在复杂的多微生物感染伤口情况下也能显著改善伤口愈合。
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 bothin vitroandin vivomodels. First, aPDT was applied to wound-relevant Gram-positive and Gram-negative bacteria in planktonic culture as the standardin vitrotest 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 anin vitromodel mimicking the wound bed conditions using fibrin-coated culture plates. Finally, we tested aPDTin vivoin 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 mu M methylene blue (generally regarded as safe for topical application on human skin) and 24 J cm(-2)pulsed red LED light. Our experiments suggest that aPDT is capable of significantly improving wound healing also in complicated polymicrobially infected wound situations.