环糊精-明胶超分子纳米颗粒的构筑及其在药物与蛋白质共传递中的应用研究

Considerable efforts has been devoted to co-delivery antitumoral biomolecules such as drugs, genes and proteins for synergestic cancer treatment. The challenges remain in this direction are the design and preparation of highly-efficient, low toxic and tumor environment responsive co-delivery systems. In this proposal, we plan to construct multidemonsional cyclodextrin-gelatin supramolecular nanoparticles (CD-G-SNPs) for co-delivery of drugs and proteins. The structural/functional parameters,e.g.,size, composition, morphology,surface potential, payload and crosslinking degree etc., of the nanoparticles are optimized by using a custom-designed high-throughput microfluidic platform.The optimal parameters provide useful information for us to prepare the supramolecular nanoparticles for biomedical applications. Furthermore, the responsiveness of the parameter-variable CD-G-SNPs toward matrix metalloproteinases (MMPs) will be studied systemically to project the relationship between structural/functional parameters and responsive kinetics. Finally, the biodistribution, antitumoral efficacy and biosafety issues will be investigated by using xenogragted mice as models to evaluate the synergestic mechanism. Altogether, this research proposal aims to develope novel strategies for preparation and optimization of supramolecular co-delivery systems for highly-efficient delivery of biomolecules in vivo for synergestic cancer therapeutics.The successful demonstration of this strategy will open new avenue for immunotherapy and personalized medicine in the future.

共传递有抗肿瘤效果的生物活性分子（包括小分子药物、基因和蛋白质）进行协同治疗成为癌症研究热点。设计与制备新型高效、低毒、肿瘤环境响应性的生物活性分子载体成为协同治疗的核心和瓶颈问题。本项目拟构筑多尺度的环糊精-明胶超分子载药纳米颗粒，实现对小分子药物和蛋白质的共包结。利用基于微流控的高通量制备和筛选平台，对环糊精-明胶载药纳米颗粒的理化参数（组成、尺寸、形貌、电荷、负载和交联度等）进行快速优化，为超分子纳米载体的设计提供理论指导。研究环糊精-明胶载药纳米颗粒对金属基质蛋白酶的特异性响应及其生物活性分子可控释放的动力学，总结纳米颗粒理化参数与响应性之间的关系，为设计可控释放的纳米药物奠定理论基础。研究环糊精-明胶载药纳米颗粒的体内的分布、药效和安全性，并对其协同治疗的机制进行初步探讨。本项目旨在为超分子纳米载药颗粒的可控构筑、快速筛选及其抗肿瘤研究提供新方法、新思路和新途径。

共传递有抗肿瘤效果的生物活性分子（包括小分子药物、基因和蛋白质）进行协同治疗成为癌症研究热点。设计与制备新型高效、低毒、肿瘤环境响应性的生物活性分子载体成为协同治疗的核心和瓶颈问题。本项目拟构筑多尺度的环糊精-明胶超分子载药纳米颗粒，实现对小分子药物和蛋白质的共包结。利用基于微流控的高通量制备和筛选平台，对环糊精-明胶载药纳米颗粒的理化参数（组成、尺寸、形貌、电荷、负载和交联度等）进行快速优化，为超分子纳米载体的设计提供理论指导。研究环糊精-明胶载药纳米颗粒对金属基质蛋白酶的特异性响应及其生物活性分子可控释放的动力学，总结纳米颗粒理化参数与响应性之间的关系，为设计可控释放的纳米药物奠定理论基础。研究环糊精-明胶载药纳米颗粒的体内的分布、药效和安全性，并对其协同治疗的机制进行初步探讨。本项目旨在为超分子纳米载药颗粒的可控构筑、快速筛选及其抗肿瘤研究提供新方法、新思路和新途径。