抗癌药物口服制剂的研发，可为癌症患者提供家庭治疗的机会，具有极大的市场潜力。口服给药需克服胃肠道、血液、肿瘤组织等形成的多重生理屏障。结合文献报道和前期基础，本项目拟选用应用前景广阔的玉米蛋白（zein）为基材，针对模型药物紫杉醇（PTX）口服递送的需求，通过二硫键将PTX与zein的-COOH相连，并在zein的-NH2端修饰靶向小分子叶酸，形成主动靶向和环境响应型前药；随后构建连续可控的自组装新技术，基于分子间相互作用，实现与卵磷脂、壳聚糖的层层复合，精准高效制备口服稳定-多途径吸收-主动靶向-环境响应释药型智能zein-DDS；结合现代表征技术和分析手段，建立微结构-性能关系，评价智能zein-DDS的体内命运，确保口服后可连续克服体内多重障碍，实现药物的有效递送。本项目选题具有很好的前瞻性和创新性，研究结果可为解决药物的口服给药难题提供新的思路和方法，具有重要的理论意义和应用价值。

Oral administration of anticancer drugs is highly desirable, because of patient preference and the opportunity to develop chronic treatment regimens. However, it faces many challenges on the gastrointestinal stability, permeation of biological barriers, cellular uptake, drug release and safety. In this proposal, zein, the major storage protein of maize, is used as the oral drug delivery system (DDS) material for paclitaxel (PTX), where great efforts are focused on its targeted physical and chemical modifications. That is, H2N-zein-COOH is conjugated with PTX via a disulfide linker (H2N-zein-S-S-PTX), which then conjugated with folic acid (FA-zein-S-S-PTX). After that, chitosan/lecithin/FA-zein-S-S-PTX nanoparticles (smart zein-DDS) are precisely constructed by layer-by-layer self-assembly. Then, the in vivo fate of the smart zein-DDS after oral administration is investigated, to confirm it can avoid the degradation at stomach and transport into the blood circulation, then reach the tumor site and get into the cancer cells by active targeting, then trigger the drug release and fulfill the precise cancer therapy. The results are promising for the enhancement of theoretical basis and methods to tackle the challenges associated with oral delivery of anticancer drugs.