Tumor targeting and therapeutic assessments of RNA nanoparticles carrying α9-nAChR aptamer and anti-miR-21 in triple-negative breast cancers

You Cheng Liao, Tzu Chun Cheng, Shih Hsin Tu, Jungshan Chang, Peixuan Guo, Li Ching Chen, Yuan-Soon Ho

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Triple-negative breast cancer (TNBC) is highly aggressive with a poor prognosis because of a lack of cell markers as drug targets. α9-Nicotinic acetylcholine receptor (nAChR) is expressed abundantly in TNBC; thus, it is a valuable biomarker for TNBC detection and treatment. In this study, we utilized thermodynamically stable three-way junction (3WJ) packaging RNA (pRNA) as the core to construct RNA nanoparticles with an α9-nAChR RNA aptamer as a targeting ligand and an anti-microRNA-21 (miR-21) as a therapeutic module. We compared the configuration of the two RNA nanoparticles and found that 3WJ-B-α9-nAChR-aptamer fluorescent RNA nanoparticles (3WJ-B-α9-apt-Alexa) exhibited better specificity for α9-nAChR in TNBC cells compared with 3WJ-C-α9-nAChR. Furthermore, 3WJ-B-α9-apt-Alexa bound more efficiently to TNBC patient-derived xenograft (PDX) tumors than 3WJ fluorescent RNA nanoparticles (3WJ-Alexa) with little or no accumulation in healthy organs after systemic injection in mice. Moreover, 3WJ-B-α9-nAChR-aptamer RNA nanoparticles carrying anti-miR-21 (3WJ-B-α9-apt-anti-miR-21) significantly suppressed TNBC-PDX tumor growth and induced cell apoptosis because of reduced miR-21 gene expression and upregulated the phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4) proteins. In addition, no pathological changes were detected upon toxicity examination of treated mice. In conclusion, the 3WJ-B-α9-nAChR-aptamer RNA nanoparticles established in this study efficiently deliver therapeutic anti-miR-21, indicating their potential as a novel TNBC therapy.

Original languageEnglish
Pages (from-to)351-366
Number of pages16
JournalMolecular Therapy Nucleic Acids
Volume33
DOIs
Publication statusPublished - Sept 12 2023

Keywords

  • fluorescence resonance energy transfer, FRET, microscopy
  • microRNA-21
  • MT: Oligonucleotides: Therapies and Applications
  • RNA aptamer
  • TNBC-PDX, triple-negative breast cancer, patient-derived xenograft
  • α9-nicotinic acetylcholine receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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