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Nanodiamond-based layer-by-layer nanohybrids mediate targeted delivery of miR-34a for triple negative breast cancer therapy

Author:
Xia, Yang, Deng, Xiongwei, Cao, Minjun, Liu, Sha, Zhang, Xiaofei, Xiao, Xiangqian, Shen, Sisi, Hu, Qin, Sheng, Wang
Source:
RSC advances 2018 v.8 no.25 pp. 13789-13797
ISSN:
2046-2069
Subject:
antineoplastic agents, apoptosis, breast neoplasms, cell proliferation, folic acid, microRNA, nanodiamonds, nanohybrids, prognosis, risk, therapeutics
Abstract:
Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer and significantly associated with poor prognosis and high risk of recurrence. miR-34a has been identified as a potent tumor suppressor whose expression is dramatically downregulated in TNBC. Currently, rectification of miRNA abnormality serves as a novel tumor therapeutic strategy. miR-34a is thus used as powerful antitumor agent for miRNA-based therapy against TNBC. However, miRNA-based antitumor therapy is challenged by effective targeted delivery of miRNA. In the present study, nanodiamond (ND), protamine (PS) and folic acid (FA) were used to construct ND-based layer-by-layer nanohybrids through a self-assembly approach for targeted miR-34a delivery in TNBC cells and xenograft TNBC tumors. We found that the targeted delivery of miR-34a remarkably suppressed cell proliferation, migration and induced the apoptosis of TNBC cells in vitro and inhibited tumor growth in vivo via down-regulating Fra-1 expression. The data suggest a great potential of ND-based nanohybrids for targeted intratumoral delivery of miR-34a for TNBC therapy.
Agid:
6183347