Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
J Photochem Photobiol B. 2017 Sep;174:150-161. doi: 10.1016/j.jphotobiol.2017.07.011. Epub 2017 Jul 24.
Multidrug resistant (MDR) bacterial infections have become a severe threat to the community health due to a progressive rise in antibiotic resistance. Nanoparticle-based photodynamic therapy (PDT) is increasingly been adopted as a potential antimicrobial option, yet the cytotoxicity associated with PDT is quite unspecific. Herein, we show Concanavalin-A (ConA) directed dextran capped gold nanoparticles (GNP-ConA) enhanced the efficacy and selectivity of methylene blue (MB) induced killing of multidrug resistant clinical isolates. Here, we show that our complex MB@GNP-ConA is effective against range of MDR clinical isolates, including Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. In our treatment modality negligible dark toxicity suggests photochemically driven process with 97% killing of MDR bacteria. GNP-ConA with monomeric form of MB departs maximum fluorescence decay time (τf: 1.7ns in HSA) and singlet oxygen (ΔΦ; 0.84) for improved activity in albumin rich infection sites. Further, the complex show least toxicity when tested against HEK293 mammalian cells. The principle component analysis (PCA) and confocal microscopy illustrates cytosolic O mediated type-II PDT as mechanism of action. Hence, MB@GNP-ConA mediated PDT is potential therapeutic approach against MDR infections and can be tailored to fight other infectious diseases.
由于抗生素耐药性的不断上升，多药耐药（MDR）细菌感染已成为对社区健康的严重威胁。基于纳米粒子的光动力疗法（PDT）越来越被视为一种潜在的抗菌选择，但 PDT 相关的细胞毒性相当不特异。在此，我们展示了伴刀豆球蛋白 A（ConA）导向的葡聚糖包裹的金纳米颗粒（GNP-ConA）增强了亚甲蓝（MB）诱导的多药耐药临床分离株杀伤的功效和选择性。在此，我们表明我们的复合物 MB@GNP-ConA 对多种 MDR 临床分离株有效，包括大肠杆菌、肺炎克雷伯菌和阴沟肠杆菌。在我们的治疗模式中，几乎没有暗毒性表明这是一个光化学驱动的过程，能实现 97%的 MDR 细菌杀伤。具有单体形式 MB 的 GNP-ConA 具有最大的荧光衰减时间（τf：HSA 中的 1.7ns）和单线态氧（ΔΦ；0.84），从而在富含白蛋白的感染部位具有更高的活性。此外，该复合物在对 HEK293 哺乳动物细胞的测试中显示出最小的毒性。主成分分析（PCA）和共聚焦显微镜表明，胞质 O 介导的 II 型 PDT 是作用机制。因此，MB@GNP-ConA 介导的 PDT 是对抗 MDR 感染的潜在治疗方法，并可针对其他传染病进行定制。
