关键词: Bacterial infection Cascade nanozymes PTT Synergistic antimicrobial therapy

Mesh : Hyaluronic Acid / chemistry pharmacology Animals Anti-Bacterial Agents / pharmacology chemistry therapeutic use Wound Healing / drug effects Bacterial Infections / drug therapy Mice Diabetes Mellitus, Experimental Antimicrobial Cationic Peptides / pharmacology chemistry Hyaluronoglucosaminidase / metabolism Cathelicidins Humans Diabetes Complications / drug therapy Nanoparticles / chemistry

来  源:   DOI:10.1016/j.ijbiomac.2024.132277

Abstract:
The high-glycemic microenvironment of diabetic wounds promotes bacterial proliferation, leading to persistent infections and delayed wound healing. This poses a significant threat to human health, necessitating the development of new nanodrug visualization platforms. In this study, we designed and synthesized cascade nano-systems modified with targeted peptide and hyaluronic acid for diabetic infection therapy. The nano-systems were able to target the site of infection using LL-37, and in the microenvironment of wound infection, the hyaluronic acid shell of the nano-systems was degraded by endogenous hyaluronidase. This precise degradation released a cascade of nano-enzymes on the surface of the bacteria, effectively destroying their cytoskeleton. Additionally, the metals in the nano-enzymes provided a photo-thermal effect, accelerating wound healing. The cascade nano-visualization platform demonstrated excellent bactericidal efficacy in both in vitro antimicrobial assays and in vivo diabetic infection models. In conclusion, this nano-system employs multiple approaches including targeting, enzyme-catalyzed therapy, photothermal therapy, and chemodynamic therapy to kill bacteria and promote healing. The Ag@Pt-Au-LYZ/HA-LL-37 formulation shows great potential for the treatment of diabetic wounds.
摘要:
糖尿病伤口的高血糖微环境促进细菌增殖,导致持续感染和伤口愈合延迟。这对人类健康构成重大威胁,需要开发新的纳米药物可视化平台。在这项研究中,我们设计并合成了靶向肽和透明质酸修饰的级联纳米系统,用于糖尿病感染治疗。纳米系统能够使用LL-37靶向感染部位,并在伤口感染的微环境中,纳米系统的透明质酸外壳被内源性透明质酸酶降解。这种精确的降解在细菌表面释放出一系列纳米酶,有效地破坏了它们的细胞骨架.此外,纳米酶中的金属提供了光热效应,加速伤口愈合.级联纳米可视化平台在体外抗菌测定和体内糖尿病感染模型中均显示出优异的杀菌功效。总之,这个纳米系统采用了多种方法,包括靶向,酶催化疗法,光热疗法,和化学动力学疗法来杀死细菌并促进愈合。Ag@Pt-Au-LYZ/HA-LL-37制剂显示出治疗糖尿病伤口的巨大潜力。
公众号