Zhao Zhanjuan, Li Yanzhou, Meng Shuai, Li Shaozeng, Wang Qiong, Liu Tianjun
Institute of Biomedical Engineering, Tianjin Key Laboratory of Biomedical Material, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, People's Republic of China.
Lasers Med Sci. 2014 May;29(3):1131-8. doi: 10.1007/s10103-013-1488-x. Epub 2013 Nov 19.
The incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) is increasing globally, making urgent the discovery of novel alternative therapies for infections. Photodynamic antimicrobial chemotherapy (PACT), based on oxidative damage to subcellular structures, has the advantage of circumventing multidrug resistance, and is becoming a potential therapeutic modality for methicillin-resistant bacteria. The key to PACT is photosensitization. This study demonstrates the efficiency of PACT using α-D-galactopyranosyl zinc phthalocyanines (T1-T4) for the photosensitization of MRSA, Escherichia coli, and Pseudomonas aeruginosa. Bacterial suspensions were illuminated with 650-nm light from a semiconductor laser at 0.2 W/cm(2), and the energy density was maintained at 6 J/cm(2) in the presence of different concentrations of photosensitizer. The treatment response was evaluated based on the numbers of bacterial colony-forming units. PACT with these phthalocyanines strongly affected MRSA, but weakly affected E. coli and P. aeruginosa. The efficiency of PACT on MRSA with these four phthalocyanine compounds decreased in the order T1 > T2 > T3 > T4. T1-PACT eliminated >99% of MRSA in a concentration range of 25-50 μM and at an energy density of 6 J/cm(2). Uptake measurements revealed that the PACT effect correlated with the bacterial uptake of the photosensitizer and that 4-30-fold more T1 than T2-T4 was taken up by the MRSA strain, which was confirmed with laser confocal microscopy. These data suggest that T1 is an efficient PACT photosensitizer for MRSA.
耐甲氧西林金黄色葡萄球菌（MRSA）的发病率在全球范围内呈上升趋势，因此迫切需要发现针对感染的新型替代疗法。基于对亚细胞结构的氧化损伤的光动力抗菌化疗（PACT）具有规避多药耐药性的优势，正成为耐甲氧西林细菌的一种潜在治疗方式。PACT的关键是光敏化。本研究证明了使用α-D-吡喃半乳糖基酞菁锌（T1-T4）对MRSA、大肠杆菌和铜绿假单胞菌进行光敏化的PACT效率。用半导体激光器发出的650纳米光以0.2W/cm²的功率照射细菌悬液，在存在不同浓度光敏剂的情况下将能量密度维持在6J/cm²。根据细菌集落形成单位的数量评估治疗反应。用这些酞菁进行的PACT对MRSA有强烈影响，但对大肠杆菌和铜绿假单胞菌影响较弱。这四种酞菁化合物对MRSA的PACT效率按T1>T2>T3>T4的顺序降低。在25-50μM的浓度范围内且能量密度为6J/cm²时，T1-PACT消除了>99%的MRSA。摄取测量表明，PACT效应与细菌对光敏剂的摄取相关，并且MRSA菌株摄取的T1比T2-T4多4-30倍，这通过激光共聚焦显微镜得到了证实。这些数据表明T1是用于MRSA的一种有效的PACT光敏剂。
