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抗体偶联和链霉素壳聚糖寡糖修饰的金纳米壳用于协同化疗-光热治疗耐药菌感染。

Antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells for synergistic chemo-photothermal therapy of drug-resistant bacterial infection.

机构信息

Department of Applied Chemistry, Kumoh National Institute of Technology, Daehak-ro 61, Gumi, Gyeongbuk 39177, Republic of Korea.

Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea.

出版信息

J Adv Res. 2023 Jun;48:87-104. doi: 10.1016/j.jare.2022.08.009. Epub 2022 Aug 28.

Abstract

Despite the many advanced strategies that are available, rapid gene mutation in multidrug-resistant bacterial infections remains a major challenge. Combining new therapeutic strategies such as chemo-photothermal therapy (PTT) with high antibacterial efficiency against drug-resistant Listeria monocytogenes (LM) is urgently needed. Here, we report synergistic chemo-PTT against drug-resistant LM based on antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells (anti-STR-CO-GNSs) as all-in-one nanotheranostic agents for the first time, which was used for accurate antibacterial applications. The anti-STR-CO-GNSs showed excellent photothermal conversion efficiency (31.97 %) and were responsive to near-infrared (NIR) and pH dual stimuli-triggered antibiotic release, resulting in outstanding chemo-photothermal effects against LM. In vitro chemo-photothermal effect of anti-STR-CO-GNSs with laser irradiation caused a greater antibacterial effect (1.37 %), resulting in more rapid killing of LM and prevention of LM regrowth. Most importantly, the mice receiving the anti-STR-CO-GNSs with laser irradiation specifically at the sites of LM infections healed almost completely, leaving only scars on the surface of the skin and resulting in superior inhibitory effects from combined chemo-PTT. Overall, our findings suggest that chemo-PTT using smart biocompatible anti-STR-CO-GNSs is a favorable potential alternative to combat the increasing threat of drug-resistant LM, which opens a new door for clinical anti-infection therapy in the future.

摘要

尽管有许多先进的策略可用,但多药耐药细菌感染的快速基因突变仍然是一个主要挑战。迫切需要将新的治疗策略(如化学-光热治疗(PTT))与针对耐药李斯特菌(LM)具有高抗菌效率的策略相结合。在这里,我们首次报道了基于抗体偶联和链霉素壳聚糖寡糖修饰的金纳米壳(anti-STR-CO-GNSs)的协同化学-PTT 对耐药 LM 的作用,作为一种集诊断和治疗于一体的纳米药物,用于精确的抗菌应用。anti-STR-CO-GNSs 表现出优异的光热转换效率(31.97%),并对近红外(NIR)和 pH 双刺激触发的抗生素释放有响应,从而对 LM 产生了出色的化学-PTT 作用。在激光照射下,anti-STR-CO-GNSs 的体外化学-PTT 作用导致更强的抗菌效果(1.37%),导致 LM 更快地被杀死,并防止 LM 再生。最重要的是,接受激光照射的抗-STR-CO-GNSs 治疗的 LM 感染部位的小鼠几乎完全治愈,皮肤表面仅留下疤痕,联合化疗-PTT 具有更好的抑制作用。总的来说,我们的研究结果表明,使用智能生物相容性的抗-STR-CO-GNSs 的化学-PTT 是对抗日益严重的耐药 LM 威胁的一种有利的替代方法,为未来的临床抗感染治疗开辟了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ff/10248803/74d946a83b3c/ga1.jpg

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