超两亲药物分子的设计与性能研究

Amphiphilic drugs directly as the building blocks to construct nanomedicine is currently a hot topic. However, the complicated chemical conjugation of drugs with functional moieties greatly prevents the mass screening and applications. In order to realize high-screening drug-based amphiphiles and the multiple stimuli-responsiveness, we are proposing to develop a new drug-based superamphiphile. Employing modular design to fabricate supramolecular host and guest molecules: modification of the hydrophobic drugs by guest molecules via disulfide bonds to construct functional prodrugs; using cyclodextrin-type supramolecular hosts to include the guests via the interaction of host-guest recognition to prepare a drug-based superamphiphile system with drug directly as the hydrophobic moiety. Furthermore, we will study the self-assembly in aqueous solution, the mechanism and the stimuli-responsiveness on morphology and drug-release. Finally, at a cell level we will evaluate the targeting ability, endocytosis pathway and cytotoxicity. This proposal, which is the interdiscipline of supramolecular chemistry and pharmaceutics, enriches the topology species of superamphiphile and narrows the gap between the concept and applications.

两亲的药物分子直接作为模块基元是目前构筑纳米药物的研究热点之一，但药物与功能基团复杂的化学连接极大制约了其大规模筛选与应用。为实现高通量制备基于药物的两亲分子并实现其多重响应性，计划发展一种新型“超两亲药物分子”。以模块化设计构筑超分子主客体化合物：利用双硫键在疏水药物分子上修饰上超分子客体，构成功能化前药，通过主客体分子识别作用与亲水的环糊精类超分子主体实现包结，可高通量得到一种药物直接作疏水端的超两亲分子体系。进而研究该体系在水溶液中自组装能力，探索自组装机理，研究其在外加刺激下的形貌学响应和可控释药性能。最后在细胞水平考察该体系的靶向功能、入胞途径和细胞毒性。本课题作为超分子化学与药剂学交叉领域，丰富了超两亲分子和两亲药物分子的拓扑结构，进一步缩短了概念与应用之间的距离。

两亲的药物分子直接作为模块基元是目前构筑纳米药物的研究热点之一，但药物与功能基团复杂的化学连接极大制约了其大规模筛选与应用。为实现高通量制备基于药物的两亲分子并实现其多重响应性，本课题发展了一种新型“超两亲药物分子”。以模块化设计构筑超分子主客体化合物：利用双硫键在疏水药物分子上修饰上超分子客体，构成功能化前药，通过主客体分子识别作用与亲水的环糊精类超分子主体实现包结，可高通量得到一种药物直接作疏水端的超两亲分子体系。该体系在水溶液中有丰富的可控自组装能力，对其自组装机理进行了探讨，研究了其在外加刺激下的形貌学响应和可控释药性能。在细胞水平考察该体系的靶向功能、入胞途径和细胞毒性测试。本课题作为超分子化学与药剂学交叉领域，丰富了超两亲分子的外沿，为母体药物功能化和药物控缓释提供了新思路。