Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Lessingstrasse 8, D-07743, Jena, Germany.
Photochem Photobiol Sci. 2011 Oct;10(10):1593-601. doi: 10.1039/c1pp05100h. Epub 2011 Jul 20.
Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.
光动力抗菌化疗（PACT）和抗菌肽（AMPs）是两种有前途的策略，可用于对抗日益增多的抗生素耐药菌。为了利用这两种策略，我们通过制备 WLBU2 修饰的脂质体，将一种新型抗菌肽（WLBU2）和一种有效的第二代光敏剂（替莫泊芬）整合到脂质体中，旨在将替莫泊芬靶向递送至细菌用于 PACT。使用功能磷脂成功地将 WLBU2 偶联到载有替莫泊芬的脂质体上。通过荧光显微镜和流式细胞术证实了替莫泊芬向细菌的传递，从而表明 WLBU2 修饰的脂质体向细菌传递的替莫泊芬比未修饰的脂质体多。因此，WLBU2 修饰的脂质体根除了所有耐甲氧西林金黄色葡萄球菌（MRSA），并在体外光动力失活试验中诱导铜绿假单胞菌减少 3.3 log（10）。这些发现表明，使用 AMP 修饰的脂质体有望实现光敏剂的细菌靶向递送，并提高局部感染中针对革兰氏阳性和革兰氏阴性细菌的 PACT 效率。
