蘑菇形拓扑高分子的合成与自组装多功能纳米孔模板控释研究

As one of the high ordered materials, nanoporous template with a large number of nanoarrays is being pursued as desirable carriers for controlled drug release based on the chemical durability and preparation reproducibility. In spite of many improvements in the application of nanoporous template as a novel drug delivery system (DDS), however, several main drawbacks are still remained, including inadequate functionality, low release adjustablity, inaccurate release kinetic equation at nanoscale, and so on. To overcome the mentioned-above problems, we propose a novel mushroom-shaped topological polymer, namely, BAC type amphiphilic linear-hyperbranched multiblock copolymers from the viewpoint of molecular design. In this polymer structure, β-cyclodextrin-containing pH-responsive linear copolymers, temperature-responsive linear copolymers, and hydrophobic long chain hyperbranched polymer serve as A, B, and C block, respectively. The multifunctional nanoporous template using A and B blocks as walls of the nanoporous and C block as the matrix can be fabricated through combined controlled macromolecular self-assembly technology and non-solvent-induced phase separation method. The advantages of such nanoporous template are that (1) The wall of nanoporous with tunable structure simultaneously possesses pH- and temperature-responsive as well as molecular recognition properties; (2) The matrix of template can be used to encapsulate drug molecules, meantime, is sensitive to ultrasonic vibration field. The above merits are expected to fulfill the subregional encapsulation and controlled release functions of nanoporous template toward drug molecules with different sizes at nanoscale level. Therefore, it is believed that the novel nanoporous template will be of great helpful for the development of DDS and the application of combined drugs in treat diseases.

纳米孔模板是一种含有大量纳米孔阵列的高度有序材料，凭借其良好的化学稳定性和制备重现性，已在药物控制释放等领域显示出广泛的应用前景。但目前用纳米孔模板进行药物释放过程中，仍然存在模板功能化程度低、释放可控性差、难以得到准确的释放动力学方程等问题。基于此，申请者从分子设计的角度出发，将含β-环糊精链节的pH响应性线形共聚物、温度响应性线形共聚物、以及疏水的长链超支化聚合物引入到同一有序的蘑菇形大分子结构中，设计合成出BAC型两亲性线形-超支化拓扑高分子新物种。通过其可控自组装行为和非溶剂引发相分离法，制备出以长链超支化聚合物为基体、纳米孔结构可调控，且具有pH、温度、超声响应性以及分子识别特性的多功能纳米孔模板。综合利用模板的可控结构和多功能性实现在纳米尺度下对不同尺寸药物分子的分区域包载和控制释放，从而为其在智能化药物释放载体的研制、运用组合药物治疗疾病等领域的应用提供实验数据和理论依据。

超支化拓扑高分子凭借其三维拓扑结构和含有大量端基官能团等结构特点在大分子自组装、生物医药等领域展现出广泛的应用前景。另一方面，超分子主客体作用基于的聚合物体系具有动态可逆特性，这将有利于实现药物载体的智能释放。本项目将超支化拓扑结构和超分子主客体作用结合起来，设计合成了一系列结构可控的功能性超分子超支化/支化拓扑高分子，深入研究了其组装参数（形貌、尺寸等）和动态组装过程调控机制，并将所制备的多功能超分子自组装体应用于药物控释和基因传输等领域。在此基础上，还研究了超支化拓扑结构或超分子作用增强的聚合物有序多孔膜的制备及其药物控释行为。本项目取得的代表性成果包括：（1）提出了“刚柔相济”的分子设计策略、“基于自分类识别的三单体聚合”新方法，解决了超分子超支化聚合过程中易发生环化、凝胶、沉淀等瓶颈问题，达到了对其结构调控的目的；（2）开拓了通过改变主客体结合位点个数或施加超声振动场来调节超分子自组装的新途径，实现了对组装体形貌、尺寸和性能的有效调控；（3）揭示了光控超分子支化共聚物组装体“囊泡-胶束-囊泡”可逆形貌转化的动态过程，证实了该组装体的“开-关”控释功能。通过本项目的研究，课题组迄今已在 Chem. Commun.（3篇）, ACS Macro Lett.（1篇）, Chem. Eur. J.（3篇）, Polym. Chem.（6篇）等期刊上正式发表SCI论文23篇，会议论文5篇；获得陕西省化学优秀青年奖1项、第三届阿达玛斯学术论文奖1项；授权中国发明专利4项；培养博士研究生4人（已毕业3人），硕士研究生4人（均已毕业）；项目负责人主办国内学术会议1次。以上研究成果被Chem. Soc. Rev., Prog. Polym. Sci., J. Am. Chem. Soc., Angew. Chem. Int. Ed., Chem. Sci., Macromolecules等国际著名SCI期刊正面引用和积极评价。