标题: 多功能性奈米双亲性几丁聚醣包覆双药系统 应用于癌症治疗
Fabrication of multifunctional chitosan based dual drug nanocarrier for application in cancer treatment
作者: 江俞谦
刘典谟
Chiang, Yu-Chian
Liu, Dean-Mo
材料科学与工程学系所
关键字: 双性几丁聚醣;非小细胞肺癌;化学疗法;共同运送;协同效应;Amphiphilic chitosan;Non-small-cell lung cancer;Chemotherapy;Co-delivery;synergistic effect
公开日期: 2017
摘要: 癌症是现今造成人类死亡的主要原因之一,然而肺癌又是众多癌症之中发生率和致死率最高的,目前非小细胞肺癌治疗方式仍以化学治疗为主。若是长时间持续给予同一药物容易使癌细胞产生多重抗药性(MDR)是肿瘤转移和治疗失败的主因。因此,开发能够有效抑制多重抗药性(MDR)的药物系统为本研究的主轴。
我们透过奈米双性几丁聚醣(CHC)自组装的特性来达到同时包覆二线抗癌药健择(dFdC)及去甲氧基姜黄素(DMC), 形成具有高包药率、生物相容性的药物载体系统。在奈米载体外嫁接特定抗体能够提供奈米粒子标靶效果,还能形成壳状结构,进而减少药物在血液循环中的释放。除此之外,在这个设计中,我们能有效调控药物浓度,使两种药物以特定比例同时到达癌细胞,以增加药物的协同效应(synergetic effect)更有效的毒杀癌细胞。
在小鼠种植异位肺癌细胞(A549)的研究中。标靶双药奈米粒子比起纯药物,表现出优异的肿瘤抑制效果,另外,我们利用急毒性实验的结果证实了标靶双药奈米粒子的生物安全性远高过纯药物,并了解其药物动力特性与体内分布情况。实验结果充分表现出此设计无论在生物安全性和功效方面都有前瞻性的治疗潜力。将在这个合并疗法(combination therapy)盛行的时代扮演重要的角色

Multi-drug resistance (MDR) in cancer cells, is the main reason for tumor metastasis and invalid treatment. Thus, to develop an anti-MDR cancer therapy become the emergency work. This research established one multifunctional dual-drug delivery system with one-pot synthesis, which combined targeting, biodegradable and dual-drug encapsulation on one nanoparticle to inhibit MDR-pathway in caner stem cells. The second-line anti-cancer drug, gemcitabine (dFdC), and the Chinese herbal extract demethoxycurcumin (DMC) were chosen and loaded in biodegradable carboxymethyl-hexanoyl chitosan (CHC) nanoparticles modified with EGFR antibody, which is the biomarker on non-small cell lung cancer, A549.
The CHC/dual-drug/anti-EGFR nanoparticle did out-standing IC50 and CI value on killing A549 compared with free dFdC and DMC combination, which meant the highly efficiency and synergy of this drug co-delivery system. In addition, CHC/dual-drug/anti-EGFR nanoparticle performed better treatment on A549 xenograft in mice than other experiment groups, indicating that this multifunctional nanocarrier may provide a new way for chemotherapy in cancer treatment.
URI: http://etd.lib.nctu.edu.tw/cdrfb3/record/nctu/#GT070451558
http://hdl.handle.net/11536/141713
显示于类别:Thesis