Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo
Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo
复制标题
硫适体结合的 CD44 靶向递送系统用于体外和体内治疗乳腺癌。
DOI：
10.3109/1061186x.2015.1077850
复制
发表时间：
2016-04-20
影响因子：
4.5
通讯作者：
Lu, Qiping
中科院分区：
文献类型：
--
作者：
Fan, Wei;Wang, Xiang;Lu, Qiping
近年来发展起来的药物递送系统的高转染效率和增强的治疗效果意味着配体修饰的纳米载体是潜在的用于乳腺癌治疗的靶向载体。本研究设计的硫适体修饰纳米粒主要由配体TA和树枝状聚酰胺胺（PAMAM）组成。由于TA可与乳腺癌中的CD44-受体结合，本研究旨在验证TA-PEG-PAMAM/miRNA（聚乙二醇-PEG）系统递送miRNA至乳腺癌细胞的安全性和可行性，体外验证其肿瘤靶向效率，并观察其系统给药至乳腺癌异种移植小鼠模型时的生物分布。在人乳腺癌荷瘤小鼠中的体内和离体成像结果表明，TA修饰能够增强NPs在乳腺癌肿瘤中的积累。我们的数据表明，TA-NPs没有诱导正常组织和重要器官的功能损伤。TA-NPs是一种安全有效的miRNA载体系统，有望在乳腺癌的临床前和临床治疗中得到广泛应用。
The high transfection efficiency and enhanced therapeutic effect of drug delivery systems developed in recent years imply that ligand-decorated nanocarriers are potentially targeted vectors for breast cancer treatment. Thioaptamer (TA)-modified nanoparticles (NPs) designed in this study mainly consisted of ligand TA and dendritic polyamidoamine (PAMAM). Knowing that TA can bind to CD44-receptors in breast cancer, this study was intended to validate the safety and feasibility of systemic miRNA delivery to breast cancer cells by TA-PEG-PAMAM/miRNA (polyethylene glycol - PEG), testify its tumor targeting efficiency in vitro, and observe its biodistribution when it was administered systemically to a xenograft mouse model of breast cancer. The in vivo and ex vivo imaging results in human breast cancer tumor-bearing mice showed that TA-modification was able to enhance the accumulation of NPs in the breast cancer tumor. Our data showed that TA-NPs did not induce functional impairment to normal tissues and vital organs. TA-NPs may prove to be a safe and effective miRNA deliver system for breast cancer treatment, and could be widely used in pre-clinical and eventually clinical arenas of breast cancer treatment.