【作者】 蔡小丽； 杜丹； 林跃河；

【Author】 Xiaoli Cai;Dan Du;Yuehe Lin;Key Laboratory of Pesticide and Chemical Biology of Ministry of Education,College of Chemistry,Central China Normal University;

【机构】 华中师范大学化学学院；

【摘要】 肺癌是我国目前死亡率第一的恶性肿瘤。近年来,随着空气污染越来越严重,肺癌死亡率不断增加^[1]。但是,传统的抗癌药物无法选择性的杀死癌细胞,药效低,水溶性等,则急需开发功能化纳米载体,将药物选择性运送到治疗部位,提高治疗效率。量子点具有优异的性质,它被广泛应用于体内和体外荧光成像中。Frangioni等人把量子点用在活体实验中^[2],不但成功定位淋巴结的位置,还通过量子点的荧光区域变化模拟淋巴细胞的实时流动。本文设计了基于ZnO QDs的pH响应的载药体系,来靶向治疗肺癌。在酸敏感,有强烈荧光的ZnO QDs表面修饰PEG来增加稳定性和兼容性。另外,量子点表面连接靶向分子HA以定向识别肺癌细胞A549表面大量表达的CD44蛋白。抗癌药物DOX不仅能和载体共价连接还能和量子点形成螯合物,使设计的载药体系有很高的载药率。在癌细胞酸性条件下,氧化锌量子点溶解,实现可控药物释放。同时,由于ZnO QDs溶解后对癌细胞产生毒性,在药物和载体的协同作用下,该载药体系能够获得较好的疗效。更多还原

【Abstract】 In this paper,we reported a ZnO quantum dots-based pH-responsive drug delivery system for intracellular drug controlled release.Acid-decomposable,luminescent aminated ZnO QDs was synthesized as nanocarriers with an average particle diameter of 3-4 nm.The dicarboxyl-terminated poly（ethylene glycol） is introduced to NH₂-ZnO QDs,which render it stable under physiological fluid.Moreover,a targeting ligand hyaluronic acid（HA） was conjugated to ZnO QDs for specifically binding to the overexpressed glycoprotein CD44 by cancer cells.Doxorubicin（DOX） as model drug was successfully loaded onto the functionalized ZnO QDs via forming metal-DOX complexes and covalent interactions.The pH-Sensitive ZnO QDs dissolved to Zn²⁺ in acidic endosome/lysosome after uptaked by cancer cells,which triggered the dissociation of metal-drug complex and a controlled DOX release.As result,a synergistic therapy was achieved due to the corporation of antitumor effect of Zn²⁺and DOX.更多还原