卵清蛋白
dna疫苗
抗原
癌症研究
免疫
免疫学
医学
作者
Bing Sun,Xiaohui Zhao,Yanheng Wu,Pei Cao,Fatemeh Movahedi,Jie Liu,Jingjing Wang,Zhi Ping Xu,Wenyi Gu
标识
DOI:10.1021/acsami.1c01401
摘要
Cancer vaccines have attracted increasing attention for their application in tumor immunotherapy. DNA vaccines are one of them that have been proven very promising with the advantages of safety, rapid design, and low cost. However, the low stability, ineffective cell internalization, and low immunostimulation hinder their wide application. Thus, developing targeted and safe systems to effectively deliver DNA vaccines becomes a vital step. In this study, we report the development of mannose- and bisphosphonate (BP)-modified calcium phosphate (CP) nanoparticles (NPs) as efficient vaccine delivery vehicles by targeting C-type lectin receptors (CLRs) on antigen-presenting cells (APCs). Using a model antigen ovalbumin (OVA)-encoded plasmid DNA (pOVA) as a model vaccine, we demonstrate that mannose-modified and BP-stabilized CP (MBCP) nanoparticles are mono-dispersed for enhanced uptake by APCs and subsequently induce OVA antigen presentation and immunostimulation. Mice immunized with MBCP-pOVA nanovaccines show a significantly stronger anti-OVA antibody response with a quicker IgG1 and IgG2a antibody production than unmodified NPs. Moreover, MBCP-pOVA immunization significantly inhibits the growth of OVA-expressing E.G7 tumor cells in C57BL/6J mice. Our data collectively suggest that the modifications to enhance the stability and targeting ability of MBCP NPs are essential for effective delivery of DNA vaccines and promote robust anti-tumor immunity.
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