纳米粒用于口服递药显现了良好的效果和前景，但前期研究主要集中于粒子尺度、表面电荷和粒子表面修饰的配基等因素对于递药效率的影响。本课题针对胃肠道多重吸收屏障，首先采用无机材料介孔硅制备三种不同形状（球、棒、盘状）的纳米粒，荷载探针药物阿霉素，并使用多粒子追踪、三维重构等技术评价不同形状纳米粒的黏液穿透和细胞摄取效率，同时在整体动物水平考察不同形状纳米粒的口服吸收效率。随后，使用超分辨率显微镜及双光子成像等技术，从不同形状纳米粒在黏液和细胞内的运动能力、运动方式等微观动力学角度探究纳米粒形状对于递药效率产生影响的机理，从而为后续纳米粒形状优化改良奠定基础，以期进一步提升优势形状纳米粒的递药效率。此外，还将采用生物相容性良好的有机材料PLGA，通过软光刻蚀方法制备不同形状纳米粒，以验证形状效应影响口服递药效率的普适性。

Nanoparticles for oral drug delivery have displayed promising results, while researches mainly focus on issues concerning particle size, zeta potentials and surface modification that will influence the efficiency during the drug delivery. In this project, we aim at multiple barriers in the gastrointestinal tract, using inorganic chemicals to fabricate mesoporous silica nanoparticles with distinct shapes (spheres, rods and discs). Doxorubicin will be utilized as a probe drug. Technologies like multiple particle tracking, three dimensional reconstruction and flow cytometry will be applied to evaluate the mucus-penetrating abilities and cellular uptake of nanoparticles. The absorption efficiency of different-shaped nanoparticles will be evaluated in the animals. In addition, high-techs like stimulated emission depletion (STED) microscopy, two photon microscopy and molecular simulation will be applied to deeply investigate the mechanisms underlying the observed shape effect that how the microcosmic dynamics affects the delivery efficiency in the mucus and epithelia based on the sight of motive ability and motion patterns. These deep insights will help us to further improve the advantageous shape, realizing the high efficiency of the certain-shaped nanoparticles. What’s more, organic PLGA nanoparticles with favorable bioavailability will be prepared via soft lithography platform to form distinct shapes as well, aiming at verifying the material universality of shape effects in oral drug delivery.