Degradable Hyaluronic Acid/Protamine Sulfate Interpolyelectrolyte Complexes as miRNA-Delivery Nanocapsules for Triple-Negative Breast Cancer Therapy

作者:Wang, Shihua; Cao, Minjun; Deng, Xiongwei; Xiao, Xiangqian; Yin, Zhaoxia; Hu, Qin; Zhou, Zhixiang; Zhang, Fang; Zhang, Ruirui; Wu, Yan*; Sheng, Wang; Zeng, Yi
来源:Advanced Healthcare Materials, 2015, 4(2): 281-290.
DOI:10.1002/adhm.201400222

摘要

Metastatic relapse is a leading cause of cancer-associated death and one of the major obstacles for effective therapy against triple-negative breast cancer. To address this problem, a miRNA-delivering nanocapsule technology based on hyaluronic acid (HA)/protamine sulfate (PS) interpolyelectrolyte complexes (HP-IPECs) is developed for efficient encapsulation and intracellular delivery microRNA-34a (miR-34a), which is a potent endogenous tumor suppressor of breast cancer. The nanocapsules are successfully generated through a self-assembly approach mediated by an electrostatic interaction. In vitro and in vivo experiments illustrate that miR-34a can be efficiently encapsulated into HP-IPECs and delivered into breast cancer cells or breast cancer tissues. Nanocomplex-assisted delivery of miR-34a induces cell apoptosis and suppresses migration, proliferation, and tumor growth of breast cancer cells via targeting CD44 and a Notch-1-signaling pathway. The obtained results suggest that HP-IPECs have a great potential as a biodegradable vector for microRNA-based therapy against triple-negative breast cancer.