Protease-stable polycationic photosensitizer conjugates between polyethyleneimine and chlorin(e6) for broad-spectrum antimicrobial photoinactivation
Protease-stable polycationic photosensitizer conjugates between polyethyleneimine and chlorin(e6) for broad-spectrum antimicrobial photoinactivation
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DOI：
10.1128/aac.50.4.1402-1410.2006
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发表时间：
2006-04-01
影响因子：
4.9
通讯作者：
Hamblin, MR
中科院分区：
文献类型：
--
作者：
Tegos, GP;Anbe, M;Hamblin, MR
我们先前的研究表明，多聚L赖氨酸与氯(E6)的共价偶联物是革兰氏阳性和革兰氏阴性细菌的有效光敏剂(PS)。聚阳离子分子结构增加了PS对不透性的革兰氏阴性细胞的结合和穿透。我们现在已经制备了一组新的第二代多阳离子偶联物，它们是氯化(E6)和三种分子形式的聚乙烯亚胺(PEI)：一个小的线型，一个小的交联体和一个大的交联体。用高压液相色谱对结合物进行了表征，并测试了它们在低强度红光照射下对一组病原微生物、革兰氏阳性金黄色葡萄球菌和化脓性链球菌、革兰氏阴性大肠埃希菌和铜绿假单胞菌以及酵母白色念珠菌的杀灭能力。这种大的交联分子有效地杀死了所有生物，而线性结合物则杀死了革兰氏阳性细菌和白色念珠菌。小的交联物是最不有效的抗菌PS，其极低的活性不能用光化学量子产率或细胞摄取减少来解释。与聚赖氨酸结合物相比，PEI结合物不被胰酶等降解赖氨酸-赖氨酸多肽键的酶降解，蛋白酶稳定性的优势以及PEI的现成表明这些分子可能优于多赖氨酸-PS结合物用于局部感染的光动力学治疗。
We previously showed that covalent conjugates between poly-L-lysine and chlorin(e6) were efficient photosensitizers (PS) of both gram-positive and gram-negative bacteria. The polycationic molecular constructs increased binding and penetration of the PS into impermeable gram-negative cells. We have now prepared a novel set of second-generation polycationic conjugates between chlorin(e6) and three molecular forms of polyethyleneimine (PEI): a small linear, a small cross-linked, and a large cross-linked molecule. The conjugates were characterized by high-pressure liquid chromatography and tested for their ability to kill a panel of pathogenic microorganisms, the gram-positive Staphylococcus aureus and Streptococcus pyogenes, the gramnegative Escherichia coli and Pseudomonas aeruginosa, and the yeast Candida albicans, after exposure to low levels of red light. The large cross-linked molecule efficiently killed all organisms, while the linear conjugate killed gram-positive bacteria and C. albicans. The small cross-linked conjugate was the least efficient antimicrobial PS and its remarkably low activity could not be explained by reduced photochemical quantum yield or reduced cellular uptake. In contrast to polylysine conjugates, the PEI conjugates were resistant to degradation by proteases such as trypsin that hydrolyze lysine-lysine peptide bonds, The advantage of protease stability combined with the ready availability of PEI suggests these molecules may be superior to polylysine-PS conjugates for photodynamic therapy of localized infections.