基于轮烷和准轮烷的纳米阀门控释系统的化学构建

Nanotechnology-based targeted therapy and drug controlled release have received extensive attention from scientists in the field of chemistry, life science and pharmaceutical science. Supramolecular nanomaterials constructed by "bottom-up" molecular assembly technique show unique properties and functions that differ from and are superior to their building blocks and have great potential in the field of sensing and nano-medicine. Molecular machines based on supramolecular assemblies, such as rotaxanes, pseudorotaxanes and etc, on the nanometer scale present various functions of those on the macro-scale, so that it can be effectively used in the microscopic field. Herein, we plan to selectively design and synthesize some supramolecular host compounds, i.e., cucurbit[n]urils, water-soluble pillar[n]arenes and modified cyclodextrins, and assemble them into functional molecular machines upon complexation with small molecules or macromolecules by supramolecular techniques, and then investigate their structures, performance, stabilities and biocompatibilities. Thus, by selecting suitable molecular machines based on (pseudo)rotaxanes and assembling them onto mesoporous nanomaterials using modern synthetic technology, we could obtain molecular nanovalves and investigate their controlled release of model drug compounds, and then develop their potential applications in the fileds of clinical drug controlled release, targeted cancer therapy, and provide possible technical support.

基于纳米技术的靶向治疗与药物可控释放越来越受到化学、生命科学和医药领域科学家的广泛关注。通过兼具"自下而上"和"从小至大"特点的分子组装技术构筑的新型超分子纳米材料显示出了其结构单元自身不具备和无法比拟的特殊性能与功能，在传感和纳米药学领域有着重要的潜在应用前景。基于轮烷和准轮烷等超分子组装体的分子机器在纳米尺度展现了宏观尺度的各种功能，并使其能有效的应用于微观领域。本项目拟选择性的设计合成葫芦脲、水溶性柱芳烃和修饰环糊精等超分子主体化合物，通过他们与小分子/高分子的包结配位作用，采用超分子制备方法将其组装成功能性的分子机器，并研究其结构、性能、稳定性和生物相容性。进而挑选合适的(准)轮烷类分子机器，运用现代合成技术将其组装到新型纳米介孔材料上制作超分子纳米阀门，并研究其对模型药物分子的可控释放，探索其在临床药物可控释放和靶向癌症治疗等领域的潜在应用并为其提供可能的重要技术支撑。

基于纳米技术的靶向治疗与药物可控释放越来越受到化学、材料科学、生命科学和医药领域科学家的广泛关注。通过兼具“自下而上”和“从小至大”特点的分子组装技术构筑的新型超分子纳米材料显示出了其结构单元自身不具备和无法比拟的特殊性能与功能，在传感和纳米药学领域有着重要的潜在应用前景。基于轮烷和准轮烷等超分子组装体的分子机器在纳米尺度展现了宏观尺度的各种功能，并使其能有效的应用于微观领域。本项目选择性的设计合成了水溶性柱芳烃、水溶性杯芳烃、葫芦脲和修饰环糊精等超分子主体化合物，通过他们与小分子/高分子的包结配位作用，采用超分子制备方法将其组装成了功能性的分子机器，并研究了其结构、性能、稳定性和生物相容性。进而挑选出了合适的(准)轮烷类分子机器，运用现代合成技术将其组装到了新型纳米介孔材料上制作了超分子纳米阀门，并研究了其对模型药物分子的可控释放，探索了其在临床药物可控释放和靶向癌症治疗等领域的潜在应用并为其提供了重要的技术支撑。相关重要结果已在Acc. Chem. Res., Chem. Soc. Rev., JACS, Adv. Mater., Chem. Sci.等期刊发表该基金标注论文45篇（通讯或第一作者论文42篇）。研究工作被Nature Chemistry、ACS Noteworthy Chemistry, Chemistry World, Chemistry Views, Materials Views China等多次正面报道。JACS入选“2013年度中国百篇最具影响国际学术论文”，项目负责人入选2015年英国皇家化学会“ChemComm新兴科学家”。