Jiangsu Province Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 31003, China.
Mater Sci Eng C Mater Biol Appl. 2020 Jan;106:110230. doi: 10.1016/j.msec.2019.110230. Epub 2019 Oct 14.
There is an urgent need for new antibacterial strategies to overcome the emergence of antibiotic resistance. Antibacterial photodynamic therapy (APDT) may be an effective method to deliver photosensitizers for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report that the photosensitizer hypocrellin A (HA) loaded into lipase-sensitive methoxy poly (ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) micelles showed high anti-MRSA activity in vitro and in vivo by PDT. Once the micelles come into contact with bacteria that secrete lipase, the PCL is degraded to release HA. Our results showed that the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of mPEG-PCL/HA micelles after light irradiation were 0.69 and 1.38 mg/L (HA concentration), respectively. In the dark, the MIC and MBC of the micelles were 250 and 500 mg/L (HA concentration), respectively. The fluorescent stain results further demonstrated the photodynamic antibacterial activity of mPEG-PCL/HA micelles. The survival rate of mice subjected to experimental acute peritonitis increased to 86% after treated with the micelles. The polymeric micelles showed low hemolytic activity and biocompatibility, simultaneously preventing aggregation in vivo and enhancing the water solubility of HA. Thus, the photosensitizer HA loaded micelles could be used as APDT for infections caused by bacteria without antibiotic resistance.
急需新的抗菌策略来克服抗生素耐药性的出现。抗菌光动力疗法（APDT）可能是一种将光敏剂递送到耐甲氧西林金黄色葡萄球菌（MRSA）感染部位的有效方法。在这里，我们报告说，载有光动力治疗剂血卟啉单甲醚（HA）的脂肪酶敏感的甲氧基聚乙二醇-嵌段-聚（ε-己内酯）（mPEG-PCL）胶束在体外和体内通过 PDT 显示出对 MRSA 的高抗活性。一旦胶束与分泌脂肪酶的细菌接触，PCL 就会被降解以释放 HA。我们的结果表明，光照后 mPEG-PCL/HA 胶束的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）分别为 0.69 和 1.38mg/L（HA 浓度）。在黑暗中，胶束的 MIC 和 MBC 分别为 250 和 500mg/L（HA 浓度）。荧光染色结果进一步证明了 mPEG-PCL/HA 胶束的光动力抗菌活性。用胶束处理实验性急性腹膜炎的小鼠的存活率增加到 86%。聚合物胶束显示出低的溶血活性和生物相容性，同时防止体内聚集并增强 HA 的水溶性。因此，载有光敏剂 HA 的胶束可用于治疗无抗生素耐药性的细菌感染的 APDT。
