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具有深层渗透和抗炎特性的 pH 响应型 HS 释放纳米消毒剂,可协同增强清除细菌生物膜和伤口感染的能力。

pH-responsive hierarchical HS-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection.

机构信息

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.

Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.

出版信息

J Nanobiotechnology. 2022 Jan 29;20(1):55. doi: 10.1186/s12951-022-01262-7.

Abstract

BACKGROUND

Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial infection is the primary cause of nosocomial infection and has long been an ongoing threat to public health. MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration.

RESULTS

A hierarchically structured hydrogen sulfide (HS)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a HS generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released HS and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of HS gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms.

CONCLUSION

ICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.

摘要

背景

耐甲氧西林金黄色葡萄球菌(MRSA)生物膜相关细菌感染是医院感染的主要原因,长期以来一直是公共卫生的持续威胁。MRSA 生物膜通常对多种抗菌策略具有抗性,主要是由于存在致密的保护屏障;因此,通过有限的药物渗透,它们可以免受先天免疫系统和抗生素治疗的影响。

结果

提出了一种具有层次结构的氢硫化物(HS)释放纳米消毒剂,它由硫化锌(ZnS)核作为 HS 发生器和吲哚菁绿(ICG)作为光增敏剂组成。这种纳米消毒剂(ICG-ZnS NPs)对生物膜微环境敏感,并通过 Zn、气体分子介导的治疗和热疗的协同作用,有效地根除了 MRSA 生物膜。受释放的 HS 和近红外光谱诱导的热疗效应的物理增强,ICG-ZnS NPs 破坏了 MRSA 生物膜的致密性,表现出显著的深穿透能力。此外,HS 气体的原位生成充分改善了过度炎症,抑制了炎症细胞因子的分泌,并促进了血管生成,从而显著加速了感染 MRSA 生物膜的皮肤伤口的体内愈合过程。

结论

ICG-ZnS NPs 与近红外激光照射联合使用,在 MRSA 生物膜中表现出显著的抗生物膜活性,可通过深穿透和抗炎作用加速愈合过程。该策略在对抗多药耐药细菌生物膜时,具有替代抗生素治疗的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca0d/8800305/92f3e47303b6/12951_2022_1262_Fig1_HTML.jpg

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