设计和构建具有肿瘤诊断和治疗功能的靶向智能型药物传输系统是实现结肠癌早期诊断及低毒高效化疗的重要措施。本项目拟通过对高分子载体的材料设计，实现对药物载体功能和性质的调控：1）基于层层自组装技术构建肠溶树脂/壳聚糖纳米微球外壳，赋予时滞型、PH敏感兼具结肠微生物酶响应功能，通过壳层的精确调控实现结肠高效定位投递功能；2）透明质酸接支谷氨酸树状大分子，阿霉素作为疏水部分通过与树状大分子的亲水基团以腙键共价结合，制备高载药量的集成载药系统并负载疏水高灵敏MnO形成纳米微球内核，实现CD44+结肠癌干细胞的靶向给药及MRI分子显像诊断功能；3）纳米复合物进入胞内体中，膜融合肽使复合物突破胞内体的包膜，阿霉素快速移送至细胞核发挥抗结肠癌效应。本项目实施可望获得一类具有我国自主知识产权、潜在临床价值的MR可视化、口服结肠定位、结肠癌干细胞靶向、癌细胞内环境响应及细胞核高效递送的多功能集成载药系统。

Theranostic agents developed based on 'all-in-one approach' will show great promise in the treatment of colon cancer, because they allow detection as well as monitoring of colon cancer at an early stage, and delivering anticancer agents over an extended period for enhanced therapeutic efficacy with low toxicity. With the help of nanoplatform technology, we will develop a series of novel smart hybrid nanomaterials that not only carry and deliver chemotherapeutics but also provide real-time imaging of drug delivery and distribution in vivo. We will systhsize poly(L-glutamic acid) dendrimers and conjugate the denerimers onto hyaluromic acid. Right before the loading of MR imaging probes-MnO nanoparticles, the poly(L-glutamic acid) dendrimers will be conjugated with doxorubicin via pH-sensitive hydrazine bonds. Once taken up by both cancer cells and cancer stem cells through CD44 receptor, the conjugated membrane fusion peptide on the nanofomula should breach membranes for fast cytosolic and nuclear delivery of doxorubicin. Subsequent layer-by-layer(LBL) self-assembly is then utilized to fabricate the enteric resin/chitosan nanospheres with time delay, pH sensing and enzyme response function for oral colon delivery. We seek to determine and delineate the sophisticated multifunctional theranostic agents with optimized properties for a range of related applications: oral colonic drug delivery, MRI visualization, cancer stem cell targeted and triggered delivery of chemotherapeutics for therapy. If successful, the proof-of-concept will allow for preclinical and clinical applications of theranostics in colon cancer therapies.