Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
School of Materials Science and Engineering, Tongji University, Shanghai 201804, China.
J Photochem Photobiol B. 2014 Jul 5;136:72-80. doi: 10.1016/j.jphotobiol.2014.04.016. Epub 2014 May 2.
In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most common multi-drug resistant bacteria in both hospital and community. The aim of this study is to investigate the selective inhibition of MRSA by a modified photosensitizer (LAEtNBS) in vitro and the efficacy of MRSA infection treatment by photodynamic therapy (PDT) with LAEtNBS in vivo. LAEtNBS was synthesized by adding a cationic photosensitizer molecule (EtNBS-COOH) and a quencher molecule to two side chains of cephalosporin, which was then shown to have similar absorption and emission wavelengths with EtNBS-COOH, but suppressed yields of fluorescence quantum and singlet oxygen. The selective inactivation and less phototoxicity of LAEtNBS, compared to that of EtNBS-COOH, were assessed and confirmed by conducting PDT to two Staphylococcus aureus strains and human skin cells at a fluence of 15 J/cm(2) with 640±10 nm LED light. Furthermore, using mouse skin wound model infected with 10(8) CFU of MRSA, we found that both LAEtNBS and EtNBS-COOH were able to treat MRSA infection and enhance wound repair. However, there was no significant difference in the two photosensitizers that might be due to the environment in vivo. Modification of the photosensitizer will be very beneficial for developing new strategies to treat drug resistant bacterial infection with less harm to host tissue.
近年来，耐甲氧西林金黄色葡萄球菌（MRSA）已成为医院和社区中最常见的多药耐药菌之一。本研究旨在探讨一种改良的光敏剂（LAEtNBS）对 MRSA 的体外选择性抑制作用，以及 LAEtNBS 光动力疗法（PDT）治疗 MRSA 感染的体内疗效。LAEtNBS 通过在头孢菌素的两条侧链上添加阳离子光敏剂分子（EtNBS-COOH）和猝灭剂分子而合成，其吸收和发射波长与 EtNBS-COOH 相似，但抑制了荧光量子产率和单线态氧的产生。通过在 15 J/cm(2)的剂量下用 640±10nm 的 LED 光对两种金黄色葡萄球菌菌株和人皮肤细胞进行 PDT，评估并证实了 LAEtNBS 与 EtNBS-COOH 相比具有选择性失活和较低的光毒性。此外，使用感染了 10(8)CFU 的 MRSA 的小鼠皮肤创面模型，我们发现 LAEtNBS 和 EtNBS-COOH 均能治疗 MRSA 感染并促进创面修复。然而，两种光敏剂之间没有显著差异，这可能是由于体内环境的原因。光敏剂的修饰将非常有利于开发治疗耐药菌感染的新策略，同时减少对宿主组织的伤害。
