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结晶钌多吡啶纳米粒子:一种具有多功能抗菌、粘附和表面固定光敏剂特性的靶向细菌感染治疗方法。

Crystalline ruthenium polypyridine nanoparticles: a targeted treatment of bacterial infection with multifunctional antibacterial, adhesion and surface-anchoring photosensitizer properties.

机构信息

School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China.

School of Chemistry, Monash University, Clayton 3800, Victoria, Australia.

出版信息

J Mater Chem B. 2021 May 12;9(18):3808-3825. doi: 10.1039/d1tb00103e.

DOI:10.1039/d1tb00103e
PMID:33979422
Abstract

Photodynamic antibacterial therapy employs nanocomposites as an alternative to traditional antibiotics for the treatment of bacterial infections. However, many of these antibacterial materials are less effective towards bacteria than traditional drugs, either due to poor specificity or antibacterial activity. This can result in needless and excessive drug use in treatments. This paper describes a multifunctional drug delivery nanoparticle (MDD-NP), Sph-Ru-MMT@PZ, based on the nanostructured-form of [Ru(bpy)2dppz] (PF6)2 (Sph-Ru), which has adhesive properties towards its microbial targets as well as surface-anchoring photosensitizer effects. The design and construction of MDD-NP is based on the adhesive properties of the outer layers of montmorillonite (MMT), which allows Sph-Ru-MMT@PZ to successfully reach its bacterial target; the outer layer of the E. coli. In addition, under 670 nm red irradiation therapy (R-IT), the surface-anchoring properties use the photosensitizer phthalocyanine zinc (PZ) to destroy the bacteria by producing reactive oxygen species (ROS) which causes cell lysis of E. coli. More importantly, Sph-Ru-MMT@PZ has no fluorescence response to live E. coli with intact cell membranes but selectively stained and demonstrated fluorescence during membrane damage of early-stage cells as well as exposure of nuclear materials at late-stage of cell lysis. Sph-Ru-MMT@PZ showed beneficial and synergistic anti-infective effects in vivo by inhibiting the E. coli infection-induced inflammatory response and eventually promoting wound healing in mice. This new strategy for high precision antibacterial therapy towards specific targets, provides an exciting opportunity for the application of multifunctional nanocomposites towards microbial infections.

摘要

光动力抗菌疗法采用纳米复合材料作为传统抗生素的替代品,用于治疗细菌感染。然而,与传统药物相比,许多这些抗菌材料对细菌的效果较差,要么是因为特异性差,要么是因为抗菌活性差。这可能导致在治疗中不必要和过度使用药物。本文描述了一种基于纳米结构形式的Ru(bpy)2dppz2(Sph-Ru)的多功能药物传递纳米粒子(MDD-NP),Sph-Ru-MMT@PZ,它对其微生物靶标具有粘附特性,并且具有表面锚固的光敏剂效应。MDD-NP 的设计和构建基于蒙脱土(MMT)的外层的粘附特性,这使得 Sph-Ru-MMT@PZ 能够成功到达其细菌靶标;大肠杆菌的外层。此外,在 670nm 红色辐射治疗(R-IT)下,表面锚固特性利用光敏剂酞菁锌(PZ)通过产生活性氧物种(ROS)来破坏细菌,导致大肠杆菌细胞裂解。更重要的是,Sph-Ru-MMT@PZ 对具有完整细胞膜的活大肠杆菌没有荧光响应,但在早期细胞的膜损伤以及晚期细胞裂解时核物质暴露时选择性染色并显示荧光。Sph-Ru-MMT@PZ 通过抑制大肠杆菌感染诱导的炎症反应,最终促进小鼠伤口愈合,在体内表现出有益的协同抗感染作用。这种针对特定靶标的高精度抗菌治疗的新策略为多功能纳米复合材料在微生物感染中的应用提供了令人兴奋的机会。

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