Moser Brittany A, Steinhardt Rachel C, Esser-Kahn Aaron P
Department of Chemistry, Chemical Engineering & Materials Science, Biomedical Engineering, University of California, Irvine, California 92697, United States.
ACS Biomater Sci Eng. 2017 Feb 13;3(2):206-213. doi: 10.1021/acsbiomaterials.6b00473. Epub 2016 Dec 1.
In the study of host-pathogen interactions, vaccines and drug delivery, particulate delivery system are widely used to mimic pathogen size, pattern recognition receptor agonist presentation, and target cells or organs. However, some of the polymeric systems used in particulate delivery have inherent inflammatory properties that are variable and nonspecific. These properties enhance their adjuvant activity, but confound the analysis of signaling mechanisms. Here, we present a method for particle coating with minimal background immune activation via passivation of the surface with silica-silane. We show herein that a silica-silane shell passivates polymer particles rendering them inert to activation of innate immune cells. The method is broadly applicable and can be used to coat polymeric particles of many different compositions. This method of silica-silane coating also allows conjugation of amine-bearing agonists and provides for controlled variation of agonist loading. Finally, we demonstrate our particles maintain and enhance qualities of known pathogens, making this a potentially general method for improving immune agonist activity.
在宿主-病原体相互作用、疫苗和药物递送的研究中，颗粒递送系统被广泛用于模拟病原体大小、模式识别受体激动剂呈递以及靶向细胞或器官。然而，颗粒递送中使用的一些聚合物系统具有固有的炎症特性，这些特性是可变的且非特异性的。这些特性增强了它们的佐剂活性，但混淆了信号传导机制的分析。在此，我们提出一种通过用硅烷化硅对表面进行钝化来实现具有最小背景免疫激活的颗粒包被方法。我们在此表明，硅烷化硅壳使聚合物颗粒钝化，使其对先天免疫细胞的激活呈惰性。该方法具有广泛的适用性，可用于包被许多不同组成的聚合物颗粒。这种硅烷化硅包被方法还允许连接含胺激动剂，并实现激动剂负载的可控变化。最后，我们证明我们的颗粒保持并增强了已知病原体的特性，使其成为一种潜在的改善免疫激动剂活性的通用方法。
