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

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.
LanguageEnglish
Article number26
Pages26-
Number of pages13
JournalPharmaceutical Research
Volume36
Issue number2
Early online date17 Dec 2018
DOIs
Publication statusPublished - 1 Feb 2019

Fingerprint

Polyglactin 910
Nanoparticles
Small Interfering RNA
Breast Neoplasms
Cell Movement
Cell Culture Techniques
Gene Knockdown Techniques
Mitogen-Activated Protein Kinase Kinases
Guanosine Triphosphate
Emulsions
Phosphatidylinositol 3-Kinases
Biological Assay
Genes
Cell Survival
Gene Expression
Cell Line

Keywords

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

Cite this

@article{15cdb417948943f89a56bc9440720648,
title = "Anti-invasive and anti-proliferative effects of shRNA-loaded poly(lactide-co-glycolide) nanoparticles following RAN silencing in MDA-MB231 breast cancer cells",
abstract = "BackgroundOverexpression 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.MethodsBiodegradable 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.ResultsshRNA-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.ConclusionResults 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.",
keywords = "Breast cancer, Intracellular delivery, Nanotechnology, PLGA, shRNA",
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Anti-invasive and anti-proliferative effects of shRNA-loaded poly(lactide-co-glycolide) nanoparticles following RAN silencing in MDA-MB231 breast cancer cells. / Sharma, Ankur; McCarron, P. A.; Matchett, Kyle; Hawthorne, Susan; El Tanani, Mohamed.

Vol. 36, No. 2, 26, 01.02.2019, p. 26-.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-invasive and anti-proliferative effects of shRNA-loaded poly(lactide-co-glycolide) nanoparticles following RAN silencing in MDA-MB231 breast cancer cells

AU - Sharma, Ankur

AU - McCarron, P. A.

AU - Matchett, Kyle

AU - Hawthorne, Susan

AU - El Tanani, Mohamed

PY - 2019/2/1

Y1 - 2019/2/1

N2 - BackgroundOverexpression 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.MethodsBiodegradable 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.ResultsshRNA-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.ConclusionResults 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.

AB - BackgroundOverexpression 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.MethodsBiodegradable 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.ResultsshRNA-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.ConclusionResults 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.

KW - Breast cancer

KW - Intracellular delivery

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