title: Degradable hyaluronic acid/protamine sulfate interpolyelectrolyte complexes as miRNA-delivery nanocapsules for triple-negative breast cancer therapy.
abstract: 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.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, No. 100 Pingleyuan, Beijing, 100124, P. R. China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
authors.forename: Minjun
authors.initials: M
authors.lastname: Cao
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Deng
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Xiao
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Yin
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.forename: Ruirui
authors.initials: R
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Wang
authors.initials: W
authors.lastname: Sheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004573:Electrolytes; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D053769:Nanocapsules / Q000737:chemistry*; D011479:Protamines / Q000737:chemistry*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D004573:Electrolytes; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D053769:Nanocapsules; D011479:Protamines; D006820:Hyaluronic Acid
keywords: breast cancer; hyaluronic acid; interpolyelectrolyte complex; microRNA-34a; tumor therapy