Molino Nicholas M, Neek Medea, Tucker Jo Anne, Nelson Edward L, Wang Szu-Wen
Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697 USA.
Department of Medicine, University of California, Irvine, CA 92697 USA.
ACS Biomater Sci Eng. 2017 Apr 10;3(4):496-501. doi: 10.1021/acsbiomaterials.7b00148. Epub 2017 Mar 14.
Efficient delivery of antigens is of paramount concern in immunotherapies. We aimed to target antigen presenting cells (APCs) by conjugating CpG oligonucleotides to an E2 protein nanoparticle surface (CpG-PEG-E2). Compared to E2 alone, we observed ~4-fold increase of APC uptake of both CpG-PEG-E2 and E2 conjugated to non-CpG DNA. Furthermore, compared to E2-alone or E2 functionalized solely with polyethylene glycol (PEG), the CpG-PEG-E2 showed enhanced lymph node retention up to at least 48 hr and 2-fold increase in APC uptake , parameters which are advantageous for vaccine success. This suggests that enhanced APC uptake of nanoparticles mediated by oligonucleotide display may help overcome delivery barriers in vaccine development.
在免疫疗法中，抗原的有效递送至关重要。我们旨在通过将CpG寡核苷酸与E2蛋白纳米颗粒表面偶联（CpG-PEG-E2）来靶向抗原呈递细胞（APC）。与单独的E2相比，我们观察到CpG-PEG-E2和与非CpG DNA偶联的E2对APC的摄取增加了约4倍。此外，与单独的E2或仅用聚乙二醇（PEG）功能化的E2相比，CpG-PEG-E2显示出增强的淋巴结滞留至少达48小时，并且APC摄取增加了2倍，这些参数对疫苗成功有利。这表明由寡核苷酸展示介导的纳米颗粒对APC摄取的增强可能有助于克服疫苗开发中的递送障碍。
