The design of drug delivery systems needs to consider biocompatibility and host body recognition for an adequate actuation. In this work, mesoporous silica nanoparticles (MSNs) surfaces were successfully modified with two silane molecules to provide mixed-charge brushes (-NH3⊕/-PO3⊝) and well evaluated in terms of surface properties, low-fouling capability and cell uptake in comparison to PEGylated MSNs. The modification process consists in the simultaneous direct-grafting of hydrolysable short chain amino (aminopropyl silanetriol, APST) and phosphonate-based (trihydroxy-silyl-propyl-methyl-phosphonate, THSPMP) silane molecules able to provide a pseudo-zwitterionic nature under physiological pH conditions. Results confirmed that both mixed-charge pseudo-zwitterionic MSNs (ZMSN) and PEG-MSN display a significant reduction of serum protein adhesion and macrophages uptake with respect to pristine MSNs. In the case of ZMSNs, this reduction is up to a 70-90% for protein adsorption and c.a. 60% for cellular uptake. This pseudo-zwitterionic modification has been focused on the aim of local treatment of bacterial infections through the synergistic effect between the inherent antimicrobial effect of mixed-charge system and the levofloxacin antibiotic release profile. These findings open promising future expectations for the effective treatment of bacterial infections through the use of mixed-charge pseudo-zwitterionic MSNs furtive to macrophages and with antimicrobial properties. STATEMENT OF SIGNIFICANCE: Herein a novel antimicrobial mixed-charge pseudo-zwitterionic MSNs based system with low-fouling and reduced cell uptake behavior has been developed. This chemical modification has been performed by the simultaneous grafting of short chain organosilanes, containing amino and phosphonate groups, respectively. This nanocarrier has been tested for local infection treatment through the synergy between the antimicrobial effect of mixed-charge brushes and the levofloxacin antibiotic release profile.

中文翻译：

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混合电荷假两性离子介孔二氧化硅纳米粒子，具有低污染和降低细胞摄取的特性。

药物输送系统的设计需要考虑生物相容性和宿主身体识别，以实现充分的驱动。在这项工作中，介孔二氧化硅纳米粒子（MSN）表面成功地用两个硅烷分子进行修饰，以提供混合电荷刷（-NH3⊕/-PO3⊝），并在表面性质、低污染能力和细胞摄取方面得到了良好的评价。与聚乙二醇化 MSN 的比较。改性过程包括同时直接接枝可水解的短链氨基（氨丙基硅烷三醇，APST）和膦酸酯基（三羟基甲硅烷基丙基甲基膦酸酯，THSPMP）硅烷分子，能够在生理条件下提供假两性离子性质pH 条件。结果证实，与原始 MSN 相比，混合电荷伪两性离子 MSN (ZMSN) 和 PEG-MSN 的血清蛋白粘附和巨噬细胞摄取均显着降低。对于 ZMSN，蛋白质吸附减少高达 70-90%，细胞摄取减少约 60%。这种伪两性离子修饰的重点是通过混合电荷系统固有的抗菌作用和左氧氟沙星抗生素释放曲线之间的协同作用来局部治疗细菌感染。这些发现为通过使用隐藏在巨噬细胞中并具有抗菌特性的混合电荷伪两性离子 MSN 来有效治疗细菌感染带来了美好的前景。意义声明：本文开发了一种基于新型抗菌混合电荷伪两性离子 MSN 的系统，该系统具有低污染和减少的细胞摄取行为。这种化学改性是通过同时接枝分别含有氨基和膦酸酯基团的短链有机硅烷来进行的。该纳米载体已通过混合电荷刷的抗菌作用与左氧氟沙星抗生素释放曲线之间的协同作用进行了局部感染治疗测试。