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投稿时间:2017-12-31 修订日期:2018-01-28
投稿时间:2017-12-31 修订日期:2018-01-28
中文摘要: 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的自由基共聚合,以聚合过程中合成高分子接枝链的疏水自组装诱导纳米尺度聚集体的形成,并通过引入具备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,红外等手段对纳米凝胶的粒径、结构、形貌性能进行表征。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。进一步地,利用近红外荧光分子和磁共振(MRI)显影分子的标记制备了荧光/MRI显影多功能复合纳米凝胶,对其显影性能进行了探讨,并证实了其优异的细胞标记能力和良好的生物相容性。
Abstract:Nanogels are nano-scaled three-dimensional networks, generally with good hydrophilicity and structural stability. Chitosan, as a natural macromolecular polysaccharide, has a great of advantages such as its non-toxicity and good biodegradability which has aroused wide attention. In this research, utilizing chitosan (CS) as the main building block, the free radical graft copolymerization was initiated at the hydroxyl carbon of chitosan and the nano-scaled aggregates were induced by the self-assembly of the hydrophobic poly(methyl acrylate) (PMA) graft chains. By introducing the redox-responsive cross-linker - diallyl disulfide (DADS) to lock the structure, the tumor sensitive chitosan-poly(methyl acrylate) (CS-PMA) nanogels were obtained at high efficiency. We named this strategy as “Graft copolymerization Induced Self-Assembly (GPISA)”. The size, morphology and structure of the nanogels were characterized by transmission electron microscopy (TEM), dynamic laser light scattering (DLS), FT-IR. Study on this facile GPISA method has proved that the sizes of the nanogels can be controlled via adjusting synthetic parameters. Furthermore, the nanogels were modified by near infrared (NIR) fluorescence molecules-Cy5.5-NHS ester and magnetic resonance imaging (MRI) enhancement molecules - Gd-DTPA to synthesize the fluorescent / MRI dual-functional nanogels. Characterization results of MRI and fluorescence imaging demonstrated that the nanogels are with great cell-labelling capability. The cell toxicity study by MTT assay confirmed the low cytotoxicity of the nanogels to lymphatic endothelial cells (LECs) and breast cancer cells (MCF-7). All these results indicated that the bio-functional nanogels had great potential as NIR/MRI probe for the diagnosis and therapy of tumor.
keywords: Chitosan Nanogels Graft copolymerization induced self-assembly (GPISA) Fluorescence imaging Magnetic resonance Imaging
文章编号:20171231001 中图分类号:O636.1 文献标志码:
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
作者 | 单位 | 邮编 |
袁晓菁 | 上海交通大学材料科学与工程学院 | |
王灏 | 上海交通大学材料科学与工程学院 | |
戴婷婷 | 上海交通大学医学院附属第九人民医院整复外科 | |
李圣利 | 上海交通大学医学院附属第九人民医院整复外科 | |
窦红静* | 上海交通大学材料科学与工程学院 | 200240 |
引用本文:
袁晓菁,王灏,戴婷婷,李圣利,窦红静.壳聚糖复合纳米凝胶的“聚合诱导自组装”制备及生物应用研究[J].功能高分子学报,DOI:10.14133/j.cnki.1008-9357.20171231001.
YUAN Xiao-jing,WANG Hao,DAI Ting-ting,LI Sheng-li,DOU Hong-jing.Study on the Graft Copolymerization Induced Self-Assembly Fabrication and Biomedical Applications of Chitosan-Based Nanogels[J].Journal of Functional Polymers,DOI:10.14133/j.cnki.1008-9357.20171231001.
袁晓菁,王灏,戴婷婷,李圣利,窦红静.壳聚糖复合纳米凝胶的“聚合诱导自组装”制备及生物应用研究[J].功能高分子学报,DOI:10.14133/j.cnki.1008-9357.20171231001.
YUAN Xiao-jing,WANG Hao,DAI Ting-ting,LI Sheng-li,DOU Hong-jing.Study on the Graft Copolymerization Induced Self-Assembly Fabrication and Biomedical Applications of Chitosan-Based Nanogels[J].Journal of Functional Polymers,DOI:10.14133/j.cnki.1008-9357.20171231001.