具有疏水微区的环境响应型多糖纳米水凝胶及其作为载体系统的研究

多糖纳米水凝胶因具有优良的生物相容性、类似生物组织的“软湿”性能及纳米材料的特殊性质，作为药物载体材料得到了广泛应用，然而，其高度亲水性的结构体系难以封装疏水性药物，在临床应用中受极大制约。本项目拟在天然多糖纳米水凝胶中引入聚合物胶束疏水微区，构建纳米两相结构体系，借助疏水微区实现疏水性抗癌药物及磁共振影像探针的有效装载，建立可视化纳米递送系统；并在水凝胶交联节点中同时引入席夫碱及二硫键，赋予其pH/redox双重响应性能，实现药物的肿瘤微环境响应性释放。结合纳米水凝胶的化学组成与其降解、载药及刺激响应性能的关联行为，完成其结构性能的优化。同时，通过磁共振影像探针的引入，赋予水凝胶纳米给药系统以成像功能，实现其体内递送路径的影像学示踪及治疗效果的无创性实时监测。本项目的实施将为肿瘤靶向治疗提供一种具有磁共振成像功能的微环境响应型水凝胶纳米载体，并对其体内药物递送及治疗效果进行在体评估。

Since their excellent biocompatibility, similar physical properties to living tissues and special properties as nanomaterials, hydrogel nanoparticles based on natural polysaccharide have been widely researched as drug delivery systems (DDS). However, traditional hydrogels are plagued by the limited loading capacity of hydrophobic drugs which play increasingly important roles in cancer therapy, owing to their very hydrophilic nature. In this project, we aim to develop a two-phase structure by introducing micellar hydrophobic microstructures into the polysaccharide-based nanogels, the resulted hydrogel nanoparticles will be used as carriers of hydrophobic antitumor drug and magnetic resonance imaging (MRI) nanoprobes, leading to a nanogel-based DDS with imaging capability. Schiff base and disulfide bonds will be then introduced into the hydrogel networks, leading to a pH/redox dual responsive nanogels for the tumor microenvironment-sensitive release of drugs. Structures and properties of the resulted nanogel will be further optimized according to their functions as drug carrier, stimuli-responsive degradation and drug release profiles. On the other side, with the help of MRI nanoprobes encapsulated in the hydrophobic microstructure, the in vitro and in vivo delivery route and therapeutic effect of the polysaccharide nanogel can be real-timely monitored using MRI technology. If successful, the proof-of-concept will lead to a promising microenvironment-sensitive drug delivery systems based on polysaccharide nanogels for MRI-guided tumor therapy, and their functions of in vivo drug delivery and tumor therapy will be investigated.