Chemistry-dependent adsorption of serum proteins onto polyanhydride microparticles differentially influences dendritic cell uptake and activation
Chemistry-dependent adsorption of serum proteins onto polyanhydride microparticles differentially influences dendritic cell uptake and activation
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DOI：
10.1016/j.actbio.2012.06.001
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发表时间：
2012-10-01
影响因子：
9.7
通讯作者：
Narasimhan, Balaji
中科院分区：
文献类型：
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作者：
Carrillo-Conde, Brenda R.;Ramer-Tait, Amanda E.;Narasimhan, Balaji
将负载抗原的微粒递送至树突状细胞（DC）可以受益于微粒本身的表面优化，从而利用材料性质并引入模拟病原体的信号。体内给药后，微粒表面特性可能会显著改变，因为蛋白质会快速吸附到其表面上。在这项工作中，我们描述了化学依赖的血清蛋白吸附模式的聚酸酐颗粒和它们的分子与DC的相互作用的影响。与两亲性聚酸酐颗粒孵育后DC上MHC II和CD 40的表达增强，以及疏水性聚酸酐颗粒增加的IL-6、TNF-α和IL-12 p40的分泌例示了假包被颗粒对DC的化学依赖性活化。蛋白质如补体成分3和IgG的存在通过以化学依赖性方式诱导DC成熟（即增加的细胞表面分子表达和细胞因子分泌）进一步增强了这些疫苗载体的佐剂性质。利用源自补体受体3缺陷型小鼠（CR 3（-/-）小鼠）的DC鉴定了在假包被颗粒和血清包被颗粒的内化中对CR 3的需要。这些研究为合理设计靶向疫苗平台提供了有价值的见解，旨在诱导强大的免疫应答并提高疫苗效力。(C)2012 Acts Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The delivery of antigen-loaded microparticles to dendritic cells (DCs) may benefit from surface optimization of the microparticles themselves, thereby exploiting the material properties and introducing signals that mimic pathogens. Following in vivo administration microparticle surface characteristics are likely to be significantly modified as proteins are quickly adsorbed onto their surface. In this work we describe the chemistry-dependent serum protein adsorption patterns on polyanhydride particles and the implications for their molecular interactions with DCs. The enhanced expression of MHC II and CD40 on DCs after incubation with amphiphilic polyanhydride particles, and the increased secretion of IL-6, TNF-alpha, and IL-12p40 by hydrophobic polyanhydride particles exemplified the chemistry-dependent activation of DCs by sham-coated particles. The presence of proteins such as complement component 3 and IgG further enhanced the adjuvant properties of these vaccine carriers by inducing DC maturation (i.e. increased cell surface molecule expression and cytokine secretion) in a chemistry-dependent manner. Utilizing DCs derived from complement receptor 3-deficient mice (CR3(-/-) mice) identified a requirement for CR3 in the internalization of both sham- and serum-coated particles. These studies provide valuable insights into the rational design of targeted vaccine platforms aimed at inducing robust immune responses and improving vaccine efficacy. (C) 2012 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved.