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

Ningqiang Gong; Xucong Teng; Jinghong Li; Xing-Jie Liang

doi:10.1021/acsami.8b18288

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.

Authors

Ningqiang Gong^{1

2

3

4}, Xucong Teng¹, Jinghong Li¹, Xing-Jie Liang^{2

3

4}

Affiliations

¹ Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology , Tsinghua University , Beijing 100084 , P. R. China.
² Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , P. R. China.
³ Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety , National Center for Nanoscience and Technology , Beijing 100190 , P. R. China.
⁴ University of Chinese Academy of Sciences , Beijing 100049 , P. R. China.

PMID: 30548064
DOI: 10.1021/acsami.8b18288

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