聚合物凝胶微球表面柔性精准修饰技术及在个性化治疗中基础问题研究

Since the precision medicine and personalized treatment technology receive more and more attention, the preparation of the versatile nano-carriers to support this technology faces more and more challenges. The main objective of this project is to design and fabricate a new kind of personalized treatment nano-carriers, our work will emphasis on the on-site assembly strategy for preparation of multifunctional nano-carriers based on the special interaction, such as the interaction between streptavidin-biotin (SA-BT) interaction, and finish to design and fabricate this new kind of multifunctional nano-drugs. In this project, we will firstly prepare the biodegradable hollow nano-gels having a polymer shell and a movable magnetic supraparticle core, wherein the magnetic core has magnetic targeting and MRI function, the hollow cavity can load ultrasonic contrast agents and other functional molecules, the polymer shell (cross-linked by disulfide or metal ions) and the cavity can load the anti-cancer drugs, the shell surface also can be modified with various targeting and other functional molecules based on the on-site flexible strategy. Thus we can develop some new technologies with our distinctive features for precise modification of the surface of magnetic hollow polymer nanocapsules, and finish the test based on the cell lines and animals. We also need to resolve the problems in fundamental science and supply the fundamental data for this new kind of on-site assembled nano-carriers in the practical theranostic application.

随着精准医学和个性化治疗技术受到医学界越来越广泛的重视，支撑该技术的多功能纳米药物载体制备技术也面临诸多新的挑战。本申请核心目标是设计和构建一类适合个性化治疗的诊治一体化载体，重点发展基于非共价键相互作用（如亲和素和生物素）的柔性精准可“即用即配”的修饰技术，完成用于个性化治疗的多功能聚合物凝胶微囊模型药物的制备，其中可移动磁核具有磁靶向和MRI造影功能，空心微腔可以负载超声波造影剂和其它功能分子，可降解的聚合物凝胶壳层（二硫键或金属离子交联）可以负载药物，表面可进行柔性精准修饰靶向及其它功能分子（满足个性化治疗需求），由此发展出聚合物凝胶微囊载体的柔性精准修饰新策略，并完成细胞和动物层面的实验评估。在此基础上，进一步解决在诊治一体化治疗中的核心基础科学问题（载体尺寸、各种修饰分子密度及特性等对药效影响），为该类材料在“即用即配”型诊治一体化制剂的临床应用奠定技术基础。

针对精准医学和个性化治疗技术对多功能纳米药物载体的需求，本项目设计和构建一系列适合个性化治疗的诊治一体化载体，重点发展了基于非共价键相互作用（如亲和素和生物素）的柔性精准可“即用即配”的修饰技术，完成了用于个性化治疗的多功能聚合物凝胶微囊模型药物的制备，其中的可移动磁核具有磁靶向和MRI造影功能，空心微腔可以负载超声波造影剂和其它功能分子，可降解的聚合物凝胶壳层（二硫键或金属离子交联）可以负载药物，表面可进行柔性精准修饰靶向及其它功能分子（满足个性化治疗需求），实验结果证明我们发展的聚合物凝胶微囊载体的柔性精准修饰新策略非常有效。同时，我们还研究了诊治一体化载体的尺寸、修饰分子密度及特性等对药效影响，为该类材料在“即用即配”型诊治一体化制剂的临床应用奠定技术基础。相关研究发表SCI论文27篇，申请中国发明专利4项，授权中国发明专利2项，参加国内外会议并做邀请报告6次。出站博士后1人，毕业博士生5名，毕业硕士生2名.