聚集诱导发光型超分子纳米控释材料的构筑及其诊疗一体化应用研究

The technologies of diagnosis and therapeutics for cancer are developed rapidly, due to the increased incidence of cancer year by year. Targeted therapies and controlled drug release have drawn remarkable attentions and studied extensively in the fields of biological science and biological medicines. Novel mesoporous materials, as the potential containers to load drug molecules, open up a broad application prospect for drug controlled release systems. Considering that the construction of functional nano-containers and the mechanism of controlled release is vital for the development of novel drug delivery systems. In this project, a series of AIE-active ligands to fabricate metal-organic frameworks will be designed and synthesized, which will be further used to construct metal mesoporous materials. Then, psedorotaxanes based on biocompatible pillar[n]arenes were synthesized and anchored onto the surface of the AIE-active metal-organic frameworks as nanovalves, resulting in the final fluorescent supramolecular hybrid materials with integrated diagnosis and therapeutics. The controlled drug release activated by external stimulus such as pH, temperature and light irradiation will be studied. Their diagnostic and therapeutic effectiveness will be investigated in vitro and in vivo, and then explore their potentials in the drug controlled release and integrated diagnosis and therapeutics for cancer.

由于癌症发病率逐年升高，癌症诊疗技术迅猛发展，基于纳米技术的靶向治疗与药物可控释放受到生命科学和生物医药等领域科学家们的广泛关注。新型多孔材料作为基本药物载体，它的发展为药物控释体系开辟了广阔的应用前景。功能药物载体材料设计构筑以及药物控释机制是开发新型药物控释体系的关键。本项目拟设计合成几类具有聚集诱导发光（AIE）特性的配体分子，通过条件控制制备新型的金属有机多孔材料。同时，选择生物相容性好的柱芳烃分子，与小分子通过非共价键作用组装成准轮烷分子机器，并通过后修饰技术将其复合于新型AIE金属有机多孔材料上，构筑集成像和治疗为一体的超分子纳米材料，研究在pH、温度、光照等外界刺激下超分子作用改变导致的药物释放机理，分别考察其在细胞和小鼠体内的细胞成像和肿瘤癌细胞抑制效果，探索其在药物控释和癌症诊疗一体化等领域的潜在价值。

由于癌症发病率逐年升高，基于纳米技术的靶向治疗与药物可控释放受到生命科学和生物医药等领域科学家们的广泛关注。新型多孔材料作为基本药物载体，它的发展为药物控释体系开辟了广阔的应用前景。功能药物载体材料设计构筑以及药物控释机制是开发新型药物控释体系的关键。通过本项目，我们构筑了基于柱芳烃超分子主客体化学的有机-无机杂化多模态诊疗材料以及超分子组装纳米前药体系。我们研究了它们在pH、温度、光照或肿瘤微环境等外界刺激下超分子作用改变导致的药物释放机理，考察了它们在细胞和小鼠体内的细胞成像和肿瘤癌细胞抑制效果。该项目展示了基于柱芳烃超分子主客体化学构筑的有机-无机杂化材料的重要应用，同时该项目也是超分子体系应用于诊疗一体化领域的重要进展，为构筑新型智能诊疗药物提供了新的设计思路。相关重要结果已在Adv. Funct. Mater.等期刊发表该基金标注论文2篇（均为第一作者）。

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