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

Background Overexpression of the RAN GTP (RAN)gene has been shown to be linked to metastatic activity of MDAMB231 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 * SusanHawthorne [email protected] 1 2 3 School of Pharmacy and Pharmaceutical Sciences, Ulster University, Cromore Road, Coleraine, Co. Londonderry BT52 1SA, UK School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast BT9 7BL, UK Institute of Cancer Therapeutics, ICT building, University of Bradford, Richmond Road, Bradford, England BD7 1DP,UK shRNA-loaded NP formulations for the treatment of breast cancer in vivo