Peer-Reviewed Journal Details
Mandatory Fields
Evans, J. C.,Malhotra, M.,Guo, J.,O'Shea, J. P.,Hanrahan, K.,O'Neill, A.,Landry, W. D.,Griffin, B. T.,Darcy, R.,Watson, R. W.,O'Driscoll, C. M.
2016
July
Nanomedicine
Folate-targeted amphiphilic cyclodextrin.siRNA nanoparticles for prostate cancer therapy exhibit PSMA mediated uptake, therapeutic gene silencing in vitro and prolonged circulation in vivo
Validated
Optional Fields
Gene therapy Psma Prostate cancer RNAi
12
8
2341
2351
In this study, a folate targeted cyclodextrin (CD) nanoparticle was prepared by co-formulating CD.siRNA complexes with DSPE-PEG5000-folate to target the prostate specific membrane antigen (PSMA). Targeted formulations showed increased uptake, relative to untargeted controls, in two prostate cancer cell lines expressing PSMA (VCaP and LNCaP). Competitive uptake studies, using excess folate, significantly reduced uptake of targeted nanoparticles in PSMA positive cell lines (P<0.001). Relative to untreated controls, folate-targeted nanoparticles significantly reduced the levels of RelA mRNA in VCaP and LNCaP cells by 44% and 22% respectively (P<0.001). In contrast there was no significant reduction in RelA mRNA in these cell lines by untargeted complexes. Pharmacokinetic (PK) data indicated that the incorporation of PEG into the formulation increased the circulation time of siRNA 8-fold. This study highlights the ability of incorporating a folate ligand into CD.siRNA nanoparticles to allow for targeted delivery of siRNA to prostate cancer cells via the PSMA.
1549-9642 (Electronic) 15
http://www.ncbi.nlm.nih.gov/pubmed/27389146
10.1016/j.nano.2016.06.014
Grant Details