Abstract：
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, in vivo 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.
摘要：
由于耐药细菌感染的微环境极其复杂，同时具有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。在这里，我们使用中性（聚乙烯吡咯烷酮-PVP）精确设计了硒纳米颗粒（SeNPs）的表面化学，阴离子(letinan-LET)和阳离子(壳聚糖-CS)表面活性剂。发现表面化学极大地影响了功能化SeNPs的生物活性，它们与耐甲氧西林金黄色葡萄球菌（MRSA）的相互作用，免疫细胞和代谢。与其他种类的SeNPs相比，具有不同代谢的LET官能化SeNPs通过诱导稳健的ROS产生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能有效激活自然杀伤（NK）细胞，并增强巨噬细胞的吞噬能力及其对细菌的杀伤活性。此外，体内研究表明，LET-SeNPs治疗高度有效地对抗MRSA感染，并通过触发更多的小鼠NK细胞促进伤口愈合，CD8+和CD4+T淋巴细胞在早期浸润到感染区域，以有效消除小鼠模型中的MRSA。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。
