Lin Jianhong, Hu Yi, Zhao Jian-Jun
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic.
J Vis Exp. 2018 Dec 13(142). doi: 10.3791/58598.
The single-wall carbon nanotube (SWCNT) is a new type of nanoparticle, which has been used to deliver multiple kinds of drugs into cells, such as proteins, oligonucleotides, and synthetic small-molecule drugs. The SWCNT has customizable dimensions, a large superficial area, and can flexibly bind with drugs through different modifications on its surface; therefore, it is an ideal system to transport drugs into cells. Long noncoding RNAs (lncRNAs) are a cluster of noncoding RNA longer than 200 nt, which cannot be translated to protein but play an important role in biological and pathophysiological processes. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved lncRNA. It was demonstrated that higher MALAT1 levels are related to the poor prognosis of various cancers, including multiple myeloma (MM). We have revealed that MALAT1 regulates DNA repair and cell death in MM; thus, MALAT1 can be considered as a therapeutic target for MM. However, the efficient delivery of the antisense oligo to inhibit/knockdown MALAT1 in vivo is still a problem. In this study, we modify the SWCNT with PEG-2000 and conjugate an anti-MALAT1 oligo to it, test the delivery of this compound in vitro, inject it intravenously into a disseminated MM mouse model, and observe a significant inhibition of MM progression, which indicates that SWCNT is an ideal delivery shuttle for anti-MALAT1 gapmer DNA.
单壁碳纳米管（SWCNT）是一种新型纳米颗粒，已被用于将多种药物递送至细胞内，如蛋白质、寡核苷酸和合成小分子药物。单壁碳纳米管具有可定制的尺寸、较大的表面积，并且可以通过其表面的不同修饰与药物灵活结合；因此，它是将药物转运到细胞内的理想系统。长链非编码RNA（lncRNA）是一类长度超过200个核苷酸的非编码RNA，其不能翻译为蛋白质，但在生物学和病理生理过程中发挥重要作用。转移相关的肺腺癌转录本1（MALAT1）是一种高度保守的lncRNA。已证明较高的MALAT1水平与包括多发性骨髓瘤（MM）在内的各种癌症的不良预后相关。我们已经揭示MALAT1在MM中调节DNA修复和细胞死亡；因此，MALAT1可被视为MM的治疗靶点。然而，在体内有效递送反义寡核苷酸以抑制/敲低MALAT1仍然是一个问题。在本研究中，我们用聚乙二醇-2000修饰单壁碳纳米管，并将抗MALAT1寡核苷酸与其偶联，在体外测试该化合物的递送，将其静脉注射到播散性MM小鼠模型中，并观察到MM进展受到显著抑制，这表明单壁碳纳米管是抗MALAT1缺口mer DNA的理想递送载体。
