反义寡核苷酸偶联纳米结构靶向 lncRNA MALAT1 抑制癌症转移。

Antisense Oligonucleotide-Conjugated Nanostructure-Targeting lncRNA MALAT1 Inhibits Cancer Metastasis.

机构信息

Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology , Tsinghua University , Beijing 100084 , P. R. China.

Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , P. R. China.

出版信息

ACS Appl Mater Interfaces. 2019 Jan 9;11(1):37-42. doi: 10.1021/acsami.8b18288. Epub 2018 Dec 18.

DOI:10.1021/acsami.8b18288

PMID:30548064

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA) located in the cell nucleus, is a critical regulator of tumor cell migration. Antisense oligonucleotides (ASOs), which can downregulate the expression level of specific RNAs, have been used in clinical for disease treatment. Herein, we constructed MALAT1-specific ASO and nucleus-targeting TAT peptide cofunctionalized Au nanoparticles, namely, ASO-Au-TAT NPs, which stabilized the fragile ASOs, enhanced nuclear internalization, and exhibited good biocompatibility. After treatment with the ASO-Au-TAT NPs, A549 lung cancer cells showed a greatly reduced MALAT1 expression level and decreased migration ability in vitro. Moreover, the ASO-Au-TAT NPs significantly reduced metastatic tumor nodule formation in vivo. Our results demonstrate that the ASO-Au-TAT nanostructures (NSs) have great potential for treatment of cancer metastasis.

摘要

转移相关肺腺癌转录本 1（MALAT1）是一种位于细胞核内的长链非编码 RNA（lncRNA），是肿瘤细胞迁移的关键调节因子。反义寡核苷酸（ASO）可下调特定 RNA 的表达水平，已在临床中用于疾病治疗。在此，我们构建了 MALAT1 特异性 ASO 和核靶向 TAT 肽共功能化的 Au 纳米粒子，即 ASO-Au-TAT NPs，其稳定了脆弱的 ASO，增强了核内内化，并表现出良好的生物相容性。用 ASO-Au-TAT NPs 处理后，A549 肺癌细胞的 MALAT1 表达水平显著降低，体外迁移能力下降。此外，ASO-Au-TAT NPs 显著减少了体内转移性肿瘤结节的形成。我们的结果表明，ASO-Au-TAT 纳米结构（NSs）在癌症转移的治疗中具有很大的潜力。