Engineering a Hollow Nanocontainer Platform with Multifunctional Molecular Machines for Tumor-Targeted Therapy in Vitro and in Vivo
Engineering a Hollow Nanocontainer Platform with Multifunctional Molecular Machines for Tumor-Targeted Therapy in Vitro and in Vivo
复制标题
利用多功能分子机器设计中空纳米容器平台，用于体外和体内肿瘤靶向治疗
DOI：
10.1021/nn404676w
复制
发表时间：
2013-11-01
期刊：
影响因子：
17.1
通讯作者：
Zhao, Yanli
中科院分区：
文献类型：
--
作者：
Luo, Zhong;Ding, Xingwei;Zhao, Yanli
为了选择性地靶向恶性细胞并消除常规化疗的严重副作用，制备了具有肿瘤特异性的生物相容性和氧化还原响应性的中空纳米容器。机械化纳米容器通过锚定机械互锁的分子来实现，即，[2]轮烷，通过二硫键连接到中空介孔二氧化硅纳米颗粒的孔上，作为细胞内谷胱甘肽触发的药物释放的中间连接体。所用的轮烷[2]主要由美国食品和药物管理局批准的四甘醇链、α-环糊精和叶酸组成。在这项研究中，机械化中空纳米容器上的叶酸基团既充当肿瘤靶向剂，又充当[2]轮烷的阻止剂。详细的研究表明，装载抗癌药物阿霉素的机械化纳米容器可以选择性地诱导肿瘤细胞的凋亡和死亡。载药纳米容器在体外增强了对肿瘤组织的靶向能力，在体内抑制肿瘤生长，副作用最小。本发明的受控和靶向药物递送系统为开发下一代纳米治疗药物以实现有效的癌症治疗铺平了道路。
In order to selectively target malignant cells and eliminate severe side effects of conventional chemotherapy, biocompatible and redox-responsive hollow nanocontainers with tumor specificity were fabricated. The mechanized nanocontainers were achieved by anchoring mechanically interlocked molecules, i.e., [2]rotaxanes, onto the orifices of hollow mesoporous silica nano-particles via disulfide bonds as intermediate linkers for intracellular glutathione-triggered drug release. The [2]rotaxane employed was mainly composed of U.S. Food and Drug Administration approved tetraethylene glycol chains, alpha-cyclodextrin, and folic acid. In this study, folate groups on the mechanized hollow nanocontainers act as both the tumor-targeting agents and stoppers of the [2]rotaxanes. Detailed investigations showed that anticancer drug doxorubicin loaded mechanized nanocontainers could selectively induce the apoptosis and death of tumor cells. The drug-loaded nanocontainers enhanced the targeting capability to tumor tissues in vitro and inhibited the tumor growth with minimal side effects in vivo. The present controlled and targeted drug delivery system paves the way for developing the next generation of nanotherapeutics toward efficient cancer treatment.