【作者】 张雪琼； 张红； 尹亮泉； 胡瑞； 邱彤； 殷以华； 熊雄； 郑化； 王群；

【Author】 Xueqiong Zhang;Hong Zhang;Liangquan Yin;Rui Hu;Tong Qiu;Yihua Yin;Xiong Xiong;Hua Zheng;Qun Wang;School of Chemistry,Chemical Engineering and Life Sciences,Wuhan University of Technology;

【机构】 武汉理工大学化工与生命科学学院；

【摘要】 本文采用羧甲基壳聚糖(Carboxymethyl Chitosan,CMCS)为大分子载体,通过酸可降解的腙键连接DNR与CMCS,制备了两亲性高分子前药CMCS-hyd-DNR。采用傅里叶红外光谱仪(FT-IR)、核磁共振波谱仪(~1H-NMR)对结构进行表征。在水介质中,自发形成的复合物纳米颗粒具有核-壳结构(CMCS和DNR为外壳和核心,)。动态光散射(DLS)和透射电子显微镜(TEM)表明所制备的纳米颗粒的形状为球形。采用HPLC法研究CMCS-hyd-DNR纳米粒在不同pH释放介质中的释药情况,研究其pH敏感性。采用CCK-8法研究该纳米系统的细胞毒性,发现CMCS-hyd-DNR纳米粒及free-DNR对肿瘤的抑制作用都表现出良好的剂量依赖性以及时间依赖性。采用激光共聚焦显微镜(CLSM)对CMCS-hyd-DNR纳米粒的细胞摄取情况进行研究,观察相同DNR浓度的CMCS-hyd-DNR纳米粒和free-DNR于不同时间点进入细胞的状况。更多还原

【Abstract】 Nanoparticles,such as polymeric micelles,are currently regarded as effective drug delivery vehicles.In this study,a series of carboxymethyl chitosan/daunorubicin(CMCS/DNR) conjugates with macromolecular carriers of different molecular weights(MWs) were prepared and structurally characterized by Fourier transform infrared spectroscopy(FT-IR) and ~1H-NMR spectroscopy.In aqueous media,the conjugates spontaneously formed nano-sized particles with core-shell structures.In addition,in vitro drug release studies demonstrated that the micelles were highly sensitive to mild acidic conditions(pH 5.0) but remained reasonably stable at pH 6.5 and pH 7.4.Importantly,cell counting kit-8(CCK-8) assays demonstrated that DNR-conjugated nanoparticles exerted a cytotoxic effect on HeLa cells.Furthermore,confocal laser scanning microscopy(CLSM) revealed that the CMCS-hyd-DNR nanosystem could efficiently deliver and release DNR in the nuclei of cancer cells.更多还原