Photosensitizer Nanodot Eliciting Immunogenicity for Photo-Immunologic Therapy of Postoperative Methicillin-Resistant Staphylococcus aureus Infection and Secondary Recurrence
Photosensitizer Nanodot Eliciting Immunogenicity for Photo-Immunologic Therapy of Postoperative Methicillin-Resistant Staphylococcus aureus Infection and Secondary Recurrence
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DOI：
10.1002/adma.202107300
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发表时间：
2022-02-08
影响因子：
29.4
通讯作者：
Yue, Bing
中科院分区：
文献类型：
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作者：
Tang, Haozheng;Qu, Xinhua;Yue, Bing
耐甲氧西林金黄色葡萄球菌（MRSA）等多重耐药菌引起的术后感染，由于其治疗效果差、复发风险高，已成为临床上一个棘手的难题。除了不完善的抗菌治疗外，成功清除病原体所需的免疫原性不足的诱导也可能导致该问题。本文中，使用光热疗法、光动力疗法和Ag+离子灭菌的超微光敏剂AgB纳米点用于在体外和体内有效地清除入侵的MRSA。还发现AgB纳米点在鼠模型中上调宿主免疫原性，并通过促进通常由应激相关反应（包括突然的温度峰值或过量的活性氧产生）诱导的危险信号的上调表达来建立免疫记忆。这些刺激增强了巨噬细胞、树突细胞、T细胞甚至记忆B细胞的抗菌作用，这通常被定义为感染相关的免疫原性细胞死亡。因此，所提出的AgB纳米点策略可以为有效治疗术后感染提供一个新的平台，同时提供一种系统的免疫策略来对抗持续性感染，从而显着降低原发性感染恢复后复发的发生率。
The treatment of postoperative infection caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has become an intractable clinical challenge owing to its low therapeutic efficacy and high risk of recurrence. Apart from imperfect antibacterial therapies, induction of insufficient immunogenicity, required for the successful clearance of a pathogen, may also contribute to the problem. Herein, an ultra-micro photosensitizer, AgB nanodots, using photothermal therapy, photodynamic therapy, and Ag+ ion sterilization, are utilized to efficiently clear invading MRSA both in vitro and in vivo. AgB nanodots are also found to upregulate host immunogenicity in a murine model and establish immunological memory by promoting the upregulated expression of danger signals that are commonly induced by stress-related responses, including sudden temperature spikes or excess reactive oxygen production. These stimulations boost the antibacterial effects of macrophages, dendritic cells, T cells, or even memory B cells, which is usually defined as infection-related immunogenic cell death. Hence, the proposed AgB nanodot strategy may offer a novel platform for the effective treatment of postoperative infection while providing a systematic immunotherapeutic strategy to combat persistent infections, thereby markedly reducing the incidence of recurrence following recovery from primary infections.