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Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles
Biomaterials ( IF 14.0 ) Pub Date : 2017-11-20 , DOI: 10.1016/j.biomaterials.2017.11.017
Sebastian O. Stead , Steven J.P. McInnes , Svjetlana Kireta , Peter D. Rose , Shilpanjali Jesudason , Darling Rojas-Canales , David Warther , Frédérique Cunin , Jean-Olivier Durand , Christopher J. Drogemuller , Robert P. Carroll , P. Toby Coates , Nicolas H. Voelcker

Dendritic cells (DC) are the most potent antigen-presenting cells and are fundamental for the establishment of transplant tolerance. The Dendritic Cell-Specific Intracellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN; CD209) receptor provides a target for dendritic cell therapy. Biodegradable and high-surface area porous silicon (pSi) nanoparticles displaying anti-DC-SIGN antibodies and loaded with the immunosuppressant rapamycin (Sirolimus) serve as a fit-for-purpose platform to target and modify DC. Here, we describe the fabrication of rapamycin-loaded DC-SIGN displaying pSi nanoparticles, the uptake efficiency into DC and the extent of nanoparticle-induced modulation of phenotype and function. DC-SIGN antibody displaying pSi nanoparticles favourably targeted and were phagocytosed by monocyte-derived and myeloid DC in whole human blood in a time- and dose-dependent manner. DC preconditioning with rapamycin-loaded nanoparticles, resulted in a maturation resistant phenotype and significantly suppressed allogeneic T-cell proliferation.



中文翻译:

用靶向多孔硅纳米粒子操纵人树突状细胞的表型和功能

树突状细胞(DC)是最有效的抗原呈递细胞,是建立移植耐受性的基础。树突状细胞特异性细胞内粘附分子-3-抓取非整联蛋白(DC-SIGN; CD209)受体为树突状细胞治疗提供了目标。具有抗DC-SIGN抗体且负载有免疫抑制剂雷帕霉素(Sirolimus)的可生物降解的高表面积多孔硅(pSi)纳米颗粒可作为靶向和修饰DC的合适平台。在这里,我们描述了载有雷帕霉素的显示pSi纳米颗粒的DC-SIGN的制备,对DC的吸收效率以及纳米颗粒诱导的表型和功能调节的程度。展示pSi纳米颗粒的DC-SIGN抗体具有良好的靶向性,并被单核细胞和髓样DC在全血中以时间和剂量依赖性方式吞噬。DC预处理雷帕霉素负载的纳米粒子,导致抗成熟的表型,并显着抑制了同种异体T细胞的增殖。

更新日期:2017-11-21
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