Anti-invasive and anti-proliferative effects of shRNA-loaded poly(lactide-co-glycolide) nanoparticles following RAN silencing in MDA-MB231 breast cancer cells

Ankur Sharma, P. A. McCarron, Kyle Matchett, Susan Hawthorne, Mohamed El Tanani

Research output: Contribution to journalArticle

2 Citations (Scopus)
8 Downloads (Pure)

Abstract

Background
Overexpression of the RAN GTP (RAN) gene has been shown to be linked to metastatic activity of MDA-MB231 human breast cancer cells by increasing Ras/MEK/ERK and PI3K/Akt/mTORC1 signalling. The aim of this study was to investigate the potential of polymeric nanoparticles to deliver two novel shRNA sequences, targeted against the RAN gene, to MDA-MB231 cells grown in culture and to assess their effects in a range of biological assays.
Methods
Biodegradable PLGA nanoparticles, loaded with shRNA-1 and shRNA-4, were fabricated using a double emulsion solvent evaporation technique and characterised for size, zeta potential and polydispersity index before testing on the MDA-MB231 cell line in a range of assays including cell viability, migration, invasion and gene knock down.
Results
shRNA-loaded nanoparticles were successfully fabricated and delivered to MDA-MB231 cells in culture, where they effectively released their payload, causing a decrease in both cell invasion and cell migration by knocking down RAN gene expression.
Conclusion
Results indicate the anti-RAN shRNA-loaded nanoparticles deliver and release biological payload to MDA-MB231 cells in culture. This works paves the way for further investigations into the possible use of anti-RAN shRNA-loaded NP formulations for the treatment of breast cancer in vivo.
Original languageEnglish
Article number26
Pages (from-to)26-
Number of pages13
JournalPharmaceutical Research
Volume36
Issue number2
Early online date17 Dec 2018
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • Breast cancer
  • Intracellular delivery
  • Nanotechnology
  • PLGA
  • shRNA

Fingerprint Dive into the research topics of 'Anti-invasive and anti-proliferative effects of shRNA-loaded poly(lactide-co-glycolide) nanoparticles following RAN silencing in MDA-MB231 breast cancer cells'. Together they form a unique fingerprint.

  • Profiles

    Cite this