Nanodiamond-based layer-by-layer nanohybrids mediate targeted delivery of miR-34a for triple negative breast cancer therapy.
Yang XiaXiongwei DengMinjun CaoSha LiuXiaofei ZhangXiangqian XiaoSisi ShenQin HuWang ShengPublished in: RSC advances (2018)
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.
Keyphrases
- long non coding rna
- cell proliferation
- poor prognosis
- long noncoding rna
- cancer therapy
- cell cycle arrest
- induced apoptosis
- pi k akt
- cell cycle
- oxidative stress
- drug delivery
- cell death
- reduced graphene oxide
- stem cells
- bone marrow
- mesenchymal stem cells
- gold nanoparticles
- stress induced
- anti inflammatory
- replacement therapy