Chemistry in Pharmaceutical Sciences Department, Inorganic and Bioinorganic Chemistry Unit, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Chemistry in Pharmaceutical Sciences Department, Inorganic and Bioinorganic Chemistry Unit, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; CIBER Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Madrid, Spain.
Acta Biomater. 2019 Jan 15;84:317-327. doi: 10.1016/j.actbio.2018.12.012. Epub 2018 Dec 6.
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 (-NH/-PO) 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.
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，以实现适当的驱动。在这项工作中，成功地用两种硅烷分子对介孔硅纳米粒子（MSNs）表面进行了修饰，提供了混合电荷刷（-NH/-PO），并从表面性质、低污染能力和细胞摄取等方面与 PEG 化 MSNs 进行了很好的比较。修饰过程包括同时直接接枝可水解短链氨基（氨丙基硅烷三醇，APST）和基于磷酸酯的（三羟基硅基丙基甲基磷酸酯，THSPMP）硅烷分子，在生理 pH 条件下能够提供假两性离子性质。结果证实，与原始 MSNs 相比，两种混合电荷假两性离子 MSNs（ZMSN）和 PEG-MSN 均显著减少了血清蛋白黏附和巨噬细胞摄取。在 ZMSNs 的情况下，这种减少高达蛋白质吸附的 70-90%，细胞摄取的 60%左右。这种假两性离子修饰的目的是通过混合电荷体系固有的抗菌作用和左氧氟沙星抗生素释放特性的协同作用，实现细菌感染的局部治疗。这些发现为通过使用对巨噬细胞具有隐匿性和抗菌特性的混合电荷假两性离子 MSNs 进行有效的细菌感染治疗开辟了广阔的前景。
本文开发了一种具有低污染和减少细胞摄取行为的新型抗菌混合电荷假两性离子 MSNs 基于系统。这种化学修饰是通过同时接枝短链有机硅烷来完成的，分别含有氨基和磷酸酯基团。这种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特性的协同作用，用于局部感染治疗的测试。
