Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are undoubtedly the ideal modality for overcoming drug resistance. Herein, we precisely engineered the surface chemistry of selenium nanoparticles (SeNPs) using neutral (polyvinylpyrrolidone-PVP), anionic (letinan-LET) and cationic (chitosan-CS) surfactants. It was found that surface chemistry greatly influenced the bioactivities of functionalized SeNPs, their interactions with methicillin-resistant Staphylococcus aureus (MRSA), immune cells and metabolisms. LET-functionalized SeNPs with distinct metabolisms exhibited the best inhibitory efficacy compared to other kinds of SeNPs against MRSA through inducing robust ROS generation and damaging bacterial cell wall. Meanwhile, only LET-SeNPs could effectively activate natural kill (NK) cells, and enhance the phagocytic capability of macrophages and its killing activity against bacteria. Furthermore, studies suggested that LET-SeNPs treatment highly effectively combated MRSA infection and promoted wound healing by triggering much more mouse NK cells, CD8 and CD4 T lymphocytes infiltrating into the infected area at the early stage to efficiently eliminate MRSA in the mouse model. This study demonstrates that the novel functionalized SeNP with dual functions could serve as an effective antibacterial agent and could guide the development of next generation antibacterial agents.

中文翻译：

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表面化学工程设计的硒纳米粒子作为杀菌和免疫调节双功能剂，用于对抗耐甲氧西林金黄色葡萄球菌感染


由于耐药细菌感染的微环境极其复杂，兼具杀菌和免疫调节活性的纳米材料无疑是克服耐药性的理想方式。在此，我们使用中性（聚乙烯吡咯烷酮-PVP）、阴离子（letinan-LET）和阳离子（壳聚糖-CS）表面活性剂精确设计了硒纳米颗粒（SeNP）的表面化学。研究发现，表面化学极大地影响了功能化 SeNP 的生物活性、它们与耐甲氧西林金黄色葡萄球菌 (MRSA)、免疫细胞和新陈代谢的相互作用。与其他类型的 SeNP 相比，具有独特代谢的 LET 功能化 SeNP 通过诱导大量 ROS 生成和破坏细菌细胞壁，对 MRSA 表现出最佳的抑制功效。同时，只有LET-SeNPs才能有效激活自然杀伤（NK）细胞，增强巨噬细胞的吞噬能力及其对细菌的杀伤活性。此外，研究表明，LET-SeNPs 治疗可有效对抗 MRSA 感染，并通过触发更多的小鼠 NK 细胞、CD8 和 CD4 T 淋巴细胞在早期浸润到感染区域，从而有效消除小鼠模型中的 MRSA，从而促进伤口愈合。这项研究表明，具有双重功能的新型功能化SeNP可以作为一种有效的抗菌剂，并可以指导下一代抗菌剂的开发。