Hierarchical targeted hepatocyte mitochondrial multifunctional chitosan nanoparticles for anticancer drug delivery
Hierarchical targeted hepatocyte mitochondrial multifunctional chitosan nanoparticles for anticancer drug delivery
复制标题
DOI：
10.1016/j.biomaterials.2015.02.001
复制
发表时间：
2015-06-01
期刊：
影响因子：
14
通讯作者：
Li, Weidong
中科院分区：
文献类型：
--
作者：
Chen, Zhipeng;Zhang, Liujie;Li, Weidong
绝大多数药物在到达其作用靶点后发挥其药理作用，然而，这些靶点主要位于细胞质或细胞内细胞器中。因此，将药物递送到特定的细胞器是实现最大治疗效果和最小副作用的关键。本文根据肿瘤的生理环境和线粒体靶向给药的要求，设计、合成并评价了一种新型的基于壳聚糖衍生物的肿瘤靶向多功能纳米粒（MNP）。智能壳聚糖纳米粒具有隐身、肝细胞靶向、多级pH响应、溶酶体逃逸和线粒体靶向等多种功能，通过功能基团的逐步脱落实现药物的靶向释放，从而实现高效的细胞内递送和线粒体定位，抑制肿瘤生长，提高抗肿瘤疗效，降低抗癌药物的毒性。它为线粒体靶向抗癌药物提供了一个安全、高效的纳米载体平台。(C)2015爱思唯尔有限公司版权所有。
The overwhelming majority of drugs exert their pharmacological effects after reaching their target sites of action, however, these target sites are mainly located in the cytosol or intracellular organelles. Consequently, delivering drugs to the specific organelle is the key to achieve maximum therapeutic effects and minimum side-effects. In the work reported here, we designed, synthesized, and evaluated a novel mitochondrial-targeted multifunctional nanoparticles (MNPs) based on chitosan derivatives according to the physiological environment of the tumor and the requirement of mitochondrial targeting drug delivery. The intelligent chitosan nanoparticles possess various functions such as stealth, hepatocyte targeting, multistage pH-response, lysosomal escape and mitochondrial targeting, which lead to targeted drug release after the progressively shedding of functional groups, thus realize the efficient intracellular delivery and mitochondrial localization, inhibit the growth of tumor, elevate the antitumor efficacy, and reduce the toxicity of anticancer drugs. It provides a safe and efficient nanocarrier platform for mitochondria targeting anticancer drug delivery. (C) 2015 Elsevier Ltd. All rights reserved.