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聚合物化学与器件几何形状对小鼠树突状细胞体外激活的协同作用。

The simultaneous effect of polymer chemistry and device geometry on the in vitro activation of murine dendritic cells.

作者信息

Petersen Latrisha K, Xue Li, Wannemuehler Michael J, Rajan Krishna, Narasimhan Balaji

机构信息

Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.

出版信息

Biomaterials. 2009 Oct;30(28):5131-42. doi: 10.1016/j.biomaterials.2009.05.069. Epub 2009 Jun 18.

Abstract

Polyanhydrides are a promising class of biomaterials for use as vaccine adjuvants and as multi-component implants. Their properties can be tailored for such applications as controlled drug release, drug stability, and/or immune regulation (adjuvant effect). Understanding the induction of immunomodulatory mechanisms of this polymer system is important for the design and development of efficacious vaccines and tissue compatible multi-component implantable devices using this polymer system. This study describes the development of a rapid multiplexed method for the investigation of the adjuvanticity of polyanhydride nanospheres and films using murine dendritic cells (DCs). To assess the immune response, cell surface markers including MHC II, CD86, CD40, and CD209 and cytokines including IL-6, IL-12p40, and IL-10 were measured. The DCs incubated with nanospheres displayed enhanced expression of all the surface markers and the production of IL-12p40 compared to DCs incubated with polymer films in a chemistry-dependent manner. This suggests that polyanhydrides of various chemistries and device geometries can be tailored to achieve desired levels of immune cell activation for specific applications. The observed biocompatibility and activation of DCs by polyanhydride devices supports their inclusion in vaccine delivery devices as well as in multi-component medical implants.

摘要

聚酸酐是一类很有前景的生物材料,可用作疫苗佐剂和多组分植入物。它们的性质可针对控释药物、药物稳定性和/或免疫调节(佐剂效应)等应用进行定制。了解该聚合物系统免疫调节机制的诱导对于设计和开发使用该聚合物系统的有效疫苗以及组织相容性多组分可植入装置非常重要。本研究描述了一种快速多重方法的开发,该方法用于使用小鼠树突状细胞(DC)研究聚酸酐纳米球和薄膜的佐剂活性。为了评估免疫反应,检测了包括MHC II、CD86、CD40和CD209在内的细胞表面标志物以及包括IL-6、IL-12p40和IL-10在内的细胞因子。与用聚合物薄膜孵育的DC相比,用纳米球孵育的DC以化学依赖的方式表现出所有表面标志物的表达增强以及IL-12p40的产生。这表明可以对各种化学组成和装置几何形状的聚酸酐进行定制,以实现针对特定应用的所需水平的免疫细胞激活。观察到的聚酸酐装置的生物相容性和对DC的激活支持将它们纳入疫苗递送装置以及多组分医疗植入物中。

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