壳聚糖复合纳米凝胶的聚合诱导自组装制备及生物应用

以生物大分子壳聚糖为主要组成基元,在壳聚糖的羟基碳上引发单体自由基共聚合。在聚合过程中疏水的合成高分子接枝链与亲水的壳聚糖分子自组装诱导形成纳米尺度的聚集体,通过引入具有肿瘤还原环境响应性的交联剂,得到了肿瘤环境响应的壳聚糖-合成高分子共聚物纳米凝胶。采用透射电镜、红外光谱等手段对纳米凝胶的粒径、结构、形貌和性能进行表征,探讨了聚合诱导自组装高效制备壳聚糖纳米凝胶的机理,证实了所得纳米凝胶粒径的可控性。进一步采用近红外荧光分子和磁共振显影（MRI）分子标记的方法制备了荧光/MRI多功能复合纳米凝胶,对凝胶显影性能进行了探讨,证实了其优异的细胞标记能力和良好的生物相容性。

Graft Copolymerization Induced Self-assembly Fabrication and Biomedical Applications of Chitosan-Based Nanogels

Nanogels are nano-scaled three-dimensional networks, generally with good hydrophilicity and structural stability. As a natural macromolecular polysaccharide, chitosan has a great number of advantages such as non-toxicity and good biodegradability which has aroused wide attention. In this paper, with chitosan (CS) as the main building block, the free radical graft copolymerization is initiated at the hydroxyl carbon of chitosan and the nano-scaled aggregates are induced by the self-assembly of the hydrophobic poly(methyl acrylate) (PMA) graft chains. By introducing the redox-responsive cross-linker diallyl disulfide (DADS), the structure is locked and the tumor sensitive chitosan-poly(methyl acrylate) (CS-PMA) nanogels are obtained at high efficiency. This strategy is named as graft copolymerization induced self-assembly (GPISA). The size, morphology and structure of the nanogels are characterized by transmission electron microscopy (TEM), dynamic laser light scattering (DLS), FT-IR. The size of the nanogels can be controlled via adjusting synthetic parameters. Moreover, the nanogels can be modified with near infrared (NIR) fluorescence molecules-Cy5.5-NHS ester and magnetic resonance imaging (MRI) enhancement molecules-Gd-DTPA, leading to fluorescent/MRI dual-functional nanogels. Characterization results of MRI and fluorescence imaging demonstrate that the nanogels show great cell-labelling capability. The cell toxicity study by MTT assay confirm the low cytotoxicity of the nanogels to lymphatic endothelial cells (LECs) and breast cancer cells (MCF-7). All these results indicate that the bio-functional nanogels have great potential as NIR/MRI probe for the diagnosis and therapy of tumor.