化疗-光热疗一体化壳聚糖-纳米金杂化药物制剂肿瘤治疗机制的研究

项目名称： 化疗-光热疗一体化壳聚糖-纳米金杂化药物制剂肿瘤治疗机制的研究

项目编号： No.31271023

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 张其清

作者单位： 中国医学科学院

项目金额： 85万元

中文摘要： 通过杂化高聚物，使金纳米棒优异的光热转换效率与药物缓释载体协同作用，实现热疗及缓释药物的化疗一体化在肿瘤治疗中具有潜在的应用价值。本项目拟结合课题组多糖纳米药物载体和纳米金可控合成的研究基础，采用巯基化聚乙烯亚胺（PEI）－CS－PEG衍生物偶联金纳米棒（GNR），构建壳聚糖（CS）基杂化GNR的化疗-光热疗一体化药物缓释载体材料；研究CS衍生物对GNR的修饰条件、机理和偶联效果及药物缓释载体材料的热敏感性、蛋白稳定性和离子稳定性等；考察杂化药物缓释载体材料对紫杉醇的负载及释放性能；考查药物缓释制剂理化性质及近红外响应性，分析近红外光对释药行为的影响；探讨杂化药物缓释制剂的细胞毒性及细胞摄取、在荷瘤鼠体内生物分布及对肿瘤抑制和杀伤的效果；研究金纳米棒优异的光热转换效率与药物缓释制剂的协同作用，揭示热疗及缓释药物化疗一体化肿瘤治疗的机制，为实现热疗及缓释药物化疗一体化肿瘤治疗奠定基础。

中文关键词： 金纳米棒；壳聚糖；肿瘤治疗；杂化材料；药物制剂

英文摘要： Gold nanorods with unique optical properties are conjugated with polymer which can transfer near-infrared light into heat and load drugs. This drug delivery system has potential applications in cancer therapy because of combining chemo- and photo-thermo therapy. Our group has the foundation on controllable synthesis of gold nanorods and nanocarriers with drugs. Therefore, we intend to prepare the chemo- and photothermal drug delivery materials which combine Chitosan (CS) and gold nanorods (GNRs). Thiol-modified polyethylene imine (PEI)-CS-PEG derivatives will be synthesized. Functional nanoparticles will be prepared by Chitosan derivatives (CS-PEG-PEI) and uniform GNRs. The modified conditions, coupling mechanism and effect, thermal sensitivity and storage stability will be studied. The loading and release properties of chitosan drug delivery system will be tested with or without near-infrared light laser, and the effect of near-infrared light will be analyzed by studying the difference of release behavior. Properties of drug delivery materials will be studied by In intro and in vivo experiments, including cytotoxicity, cellular uptake, biodistribution and tumor suppression. Furthermore, the synergistic effect of chemo- and photothermal therapy will be researched, and the mechanism on tumor therapy with hybrid p

英文关键词： Gold nanorods；Chitosan； Tumor therapy；Hybrid nanomaterial；Drug delivery system