Efficient delivery of anti-miR-210 using Tachyplesin, a cell penetrating peptide, for glioblastoma treatment
Efficient delivery of anti-miR-210 using Tachyplesin, a cell penetrating peptide, for glioblastoma treatment
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DOI：
10.1016/j.ijpharm.2019.118789
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发表时间：
2019-12-15
影响因子：
5.8
通讯作者：
Kulshreshtha, Ritu
中科院分区：
文献类型：
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作者：
Jana, Anirban;Narula, Pankhuri;Kulshreshtha, Ritu
微小RNA（miRNA）的水平在包括胶质母细胞瘤（GBM）在内的各种疾病中发生改变，并且这种改变可能对癌细胞的各种标志具有广泛的影响。MiR 210在GBM中过表达，并作为致癌miRNA发挥作用。抗miR 210疗法前景广阔，但其有效递送仍然是一个重大挑战。我们在这里的工作探索了Tachyplesin（Tpl），一种细胞穿透抗菌肽，作为抗miR 210的纳米载体的新作用。Tpl与抗miR 210以1：25和1：50（抗miR：Tpl）重量比静电相互作用以形成复合物，并将抗miR 210有效地递送到作为2D和3D球状体模型培养的GBM细胞内。用复合物处理GBM细胞显著抑制miR 210水平（类似于90%）、增殖、迁移和球体形成能力，并诱导凋亡，如通过增加的半胱天冬酶3/7和ROS水平所证明的。还发现用抗miR 210：Tpl复合物预处理的GBM细胞对TMZ介导的作用敏感。GBM细胞中复合物的摄取诱导了miR 210靶向肿瘤抑制基因NeuroD 2和HIF 3A的水平。总的来说，我们的工作揭示了Tpl在胶质瘤细胞中的新颖且有效的miRNA递送能力，为治疗GBM和潜在的其他癌症带来了巨大的希望。
The levels of microRNAs (miRNAs) are altered in various diseases including glioblastoma (GBM) and this alteration may have widespread effects on various hallmarks of cancer cells. MiR210 is overexpressed in GBM and functions as an oncogenic miRNA. Anti-miR210 therapy holds great promise but its efficient delivery remains a major challenge. Our work here explores a novel role of Tachyplesin (Tpl), a cell-penetrating antimicrobial peptide, as a nanocarrier for anti-miR210. Tpl electrostatically interacts with anti-miR210 at 1:25 and 1:50 (anti-miR:Tpl) weight ratios to form a complex and efficiently delivers anti-miR210 inside GBM cells cultured as 2D and 3D spheroid model. Treatment of GBM cells with the complex significantly inhibited miR210 levels (similar to 90%), proliferation, migration and spheroid formation ability and induced apoptosis as evident by increased levels of caspase 3/7 and ROS. GBM cells pre-treated with anti-miR210:Tpl complex were also found to be sensitive to TMZ mediated action. Uptake of the complex in GBM cells induced the levels of miR210 targeted tumor suppressor genes, NeuroD2 and HIF3A. Overall, our work reveals a novel and efficient miRNA delivery ability of Tpl in glioma cells, holding a great promise for treatment of GBM and potentially for other cancers.