聚合物微囊由于理化性质可调在药物传递系统越来越受到重视。虽然研究表明载体理化性质与细胞摄取及其药效具有密切关系，然而微囊力学性质及其几何形貌对细胞摄取及细胞内定位影响还有待深入研究。层层自组装（LbL）法制备微囊可依据模板及沉积层数精确控制微囊微观形貌及力学性质，是系统研究药物载体理化性质对细胞摄取影响的理想模型。本项目在前期丝素蛋白杂化微囊及聚合物非球形药物载体研究基础上以不同尺寸的球形、非球形PLGA微粒为模板，用LbL法制备微观形貌可控、力学性质可调的丝素蛋白微囊；系统考察RAW264.7细胞对不同微囊摄取速度、摄取量以及内化后细胞内定位及其机制；阐明载体的理化性质影响细胞摄取行为的规律，设计适体修饰的具有长循环特性和载基因近核周分布的微囊，并评价其靶向分布及转染效率。深入研究微囊与细胞之间的相互作用，既可充实细胞摄取机制，也为合理设计适应不同需求的药物载体提供科学依据。

Polymer capsules have attracted increasing interest in drug delivery system due to the tunable physicochemical properties. Although research indicates that physicochemical properties of drug carriers closely relate with cellular uptake and their effect, the impact of the mechanical properties and geometrical morphology of microcapsules on cell internalization and intracellular fate need further study. However, the impact of particle physicochemical properties on the cellular uptake process has not yet all reveal. Due to the morphology and mechanical properties of LbL-based capsules can be precisely controlled by varying the template cores, thickness and composition of the shell, capsules become ideal model to systemically study the correlationship between physic-chemical properties of capsule and cellular uptake. This project is mainly based on our previous study of silk-based capsules and polylactide-based drug carriers. First, we synthesize silk/PLL capsules with controllable morphology and tunable stiffness from spherical, non- spherical PLGA templates using LbL technique. Second, we systemically examine the rate and volume of cellular uptake after feeding capsules with different size, shape and stiffness to RAW264.7 cell, analyze the intracellular distribution after cell internalization and investigate its mechanism. Third, we explain the law between physical, chemical properties of drug carriers and cellular uptake behavior, design long circulating aptamer-guedid microcapsules and plasmid-loaded microcapsules with perinuclear accumulation, and then evaluate their targeted delivery properties. Finally, this research tries to deeply understand the interaction between microcapsules and cells, enrich the mechanism of cellular uptake, and provide science guidance for reasonable design and optimization of drug carriers adapt to the different needs.