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

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

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.

Keywords: MALAT1; cancer metastasis; gene therapy; long noncoding RNA; nanostructure.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Animals
  • Drug Delivery Systems*
  • Gold* / chemistry
  • Gold* / pharmacology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Metal Nanoparticles* / chemistry
  • Metal Nanoparticles* / therapeutic use
  • Mice
  • Neoplasm Metastasis
  • Oligonucleotides, Antisense* / chemistry
  • Oligonucleotides, Antisense* / genetics
  • Oligonucleotides, Antisense* / pharmacology
  • Peptides / chemistry
  • Peptides / pharmacology
  • RNA, Long Noncoding* / antagonists & inhibitors
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Neoplasm* / antagonists & inhibitors
  • RNA, Neoplasm* / genetics
  • RNA, Neoplasm* / metabolism
  • Xenograft Model Antitumor Assays
  • tat Gene Products, Human Immunodeficiency Virus / chemistry
  • tat Gene Products, Human Immunodeficiency Virus / pharmacology

Substances

  • MALAT1 long non-coding RNA, human
  • Oligonucleotides, Antisense
  • Peptides
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • tat Gene Products, Human Immunodeficiency Virus
  • Gold