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通过具有纳米局部高热的细菌靶向聚多巴胺纳米颗粒对耐甲氧西林细菌进行光热杀灭

Photothermal Killing of Methicillin-Resistant by Bacteria-Targeted Polydopamine Nanoparticles with Nano-Localized Hyperpyrexia.

作者信息

Hu Dengfeng, Zou Lingyun, Li Bochao, Hu Mi, Ye Wanying, Ji Jian

机构信息

MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.

出版信息

ACS Biomater Sci Eng. 2019 Oct 14;5(10):5169-5179. doi: 10.1021/acsbiomaterials.9b01173. Epub 2019 Sep 16.

Abstract

Bacterial infections caused by antibiotic-resistant pathogens have become intractable problems to public health. Therefore, there is an imperious demand for developing new approaches to effectively kill antibiotic-resistant bacteria. In this work, we report a kind of bacteria-targeted polydopamine nanoparticle exhibiting great photothermal killing ability toward methicillin-resistant (MRSA) by nano-localized hyperpyrexia under low-power near-infrared (NIR) light irradiation. These bacteria-targeted nanoparticles (PDA-PEG-Van) are prepared by modifying polydopamine nanoparticles with thiol-poly(ethylene glycol) (mPEG-SH) and vancomycin (Van) molecules. The PEG shell endows the nanoparticles with excellent long-term circulation stability. Due to the multivalent hydrogen-bond interactions between vancomycin and the MRSA cell wall, the vancomycin-modified polydopamine nanoparticles can specifically target MRSA rather than mammalian cells. These bacteria-targeted nanoparticles are employed as a nano-localized heat source to kill MRSA via disrupting the bacterial cell wall and membrane under irradiation of low-power NIR light. More importantly, the surrounding healthy tissues suffer bare damage, owing to the absence of any targeting effect of PDA-PEG-Van toward mammalian cells and the low power of NIR light used in the therapeutic process. Given the above advantages, the bacteria-targeted polydopamine nanoparticles proposed in this work show tremendous potential to treat MRSA infections, because they can effectively limit localized heating in the infection sites to kill bacteria and cut down damage to healthy tissues.

摘要

由抗生素耐药性病原体引起的细菌感染已成为公共卫生领域棘手的问题。因此,迫切需要开发新方法来有效杀灭耐药细菌。在这项工作中,我们报道了一种细菌靶向的聚多巴胺纳米颗粒,在低功率近红外(NIR)光照射下,通过纳米局部热疗对耐甲氧西林金黄色葡萄球菌(MRSA)表现出强大的光热杀伤能力。这些细菌靶向纳米颗粒(PDA-PEG-Van)是通过用硫醇-聚(乙二醇)(mPEG-SH)和万古霉素(Van)分子修饰聚多巴胺纳米颗粒制备的。PEG外壳赋予纳米颗粒优异的长期循环稳定性。由于万古霉素与MRSA细胞壁之间存在多价氢键相互作用,万古霉素修饰的聚多巴胺纳米颗粒可以特异性靶向MRSA而非哺乳动物细胞。这些细菌靶向纳米颗粒被用作纳米局部热源,在低功率NIR光照射下通过破坏细菌细胞壁和细胞膜来杀死MRSA。更重要的是,由于PDA-PEG-Van对哺乳动物细胞没有任何靶向作用,且治疗过程中使用的NIR光功率较低,周围的健康组织几乎没有受到损伤。鉴于上述优点,本文提出的细菌靶向聚多巴胺纳米颗粒在治疗MRSA感染方面显示出巨大潜力,因为它们可以有效地将局部加热限制在感染部位以杀死细菌,并减少对健康组织的损伤。

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