基于蛋白质组学策略的纳米载体跨多级肠粘膜屏障转运的分子调控机制研究

纳米技术为解决难溶性药物或生物大分子药物的口服吸收及递送问题带来了巨大的机遇，但是关于口服纳米载体的吸收及转运机制研究尚不完善，大量研究依然停留于囊泡水平，同时忽略了作为肠粘膜组成部分的粘膜下层细胞对吸收转运的影响。为解决这些问题，本项目拟构建包括肠上皮细胞单层和粘膜下层细胞在内的多级细胞转运模型，选择聚合物纳米粒和无机纳米载体作为研究对象，利用蛋白质组学技术从分子水平考察纳米载体在转运过程中的胞内蛋白表达变化，阐明转运相关分子调控网络。项目同时利用蛋白质组学技术对转运过程中胞内蛋白在纳米载体表面的吸附进行了分析鉴定，并评估其对粘膜下层细胞功能的影响。该项目创新性显著，对于揭示纳米载体跨膜转运的分子机理有重要意义。本研究团队在纳米载体细胞转运机制以及蛋白质组学分析方面具有丰富的经验和坚实的基础，科研力量强，完成可行性高。

Nanotechnology brings great opportunities to solve the problems of oral absorption and delivery for poorly water-soluble or biomacromolecule drugs. However, the absorption and transportation mechanisms of oral nanocarriers are still unclear. Recently, a lot of researches focus on exploring the transport mechanisms of nanocarriers in vesicle level, but neglect the influence of intestinal submucous cells, which are important components of mucosa. To solve these problems, we will prepare polymer nanoparticles and inorganic nanocarriers as models, construct multistage intestinal mucosal barrier including enterocyte and submucous cells, investigate the intracellular protein expressions during transportations of nanocarriers by utilizing proteomic technology, and finally illuminate the molecular regulation network. Additionally, we will use proteomic technology to identify proteins that adsorb on nanocarrier surface during the transportation, and evaluate the influence of protein corona on the activities and functions of submucous cells. The project has obvious novelty, with great significance to clarify the mechanisms of how nanocarriers transport across intestinal mucosa. We have rich experience and solid foundation on nanoparticle transport mechanism and proteomics analysis. Moreover, we have a rational team and great feaibility to accomplish the project.