CL4-modified exosomes deliver lncRNA DARS-AS1 siRNA to suppress triple-negative breast cancer progression and attenuate doxorubicin resistance by inhibiting autophagy

Xinli Liu, Ge Zhang, Tongyao Yu, Jie Liu, Xiaoxia Chai, Dachuan Yin*, Chenyan Zhang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

12 Citations (Scopus)

Abstract

Triple-negative breast cancer (TNBC) is a fatal disease. Drug resistance and the lack of effective drugs are the leading causes of death in patients with TNBC. Recently, long non-coding RNAs have been proven to be effective drug design targets owing to their high tissue specificity; however, an effective drug delivery system is necessary for their clinical application. In this study, we constructed a novel nanodrug delivery system based on the epidermal growth factor receptor (EGFR)-targeted aptamer CL4-modified exosomes (EXOs-CL4) for the targeted delivery of aspartyl-tRNA synthetase-antisense RNA 1 (DARS-AS1) small interfering RNA (siRNA) and doxorubicin (DOX) to TNBC cells in vitro and in vivo. This delivery system exerted potent anti-proliferation, anti-migration, and pro-apoptotic effects on TNBC cells. Silencing DARS-AS1 increased the sensitivity of TNBC cells to DOX by suppressing the transforming growth factor-β (TGF-β)/Smad3 signaling pathway-induced autophagy, thereby enhancing the synergetic antitumor effects. Collectively, our findings revealed that EXOs-CL4-mediated delivery of DARS-AS1 siRNA can be used as a new treatment strategy for DOX-resistant TNBC. Moreover, EXOs-CL4 can be used as effective drug delivery systems for targeted TNBC therapy.

Original languageEnglish
Article number126147
Number of pages14
JournalInternational Journal of Biological Macromolecules
Volume250
Early online date5 Aug 2023
DOIs
Publication statusPublished - 1 Oct 2023

Scopus Subject Areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

User-Defined Keywords

  • Autophagy
  • Chemosensitivity
  • CL4-modified exosomes (EXOs-CL4)
  • Exosome (EXOs)
  • Triple-negative breast cancer (TNBC)

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