Type

Journal Article

Authors

Caitriona M O' Driscoll
Raphael Darcy
Fergal J O'Brien
Caroline M Curtin
Michael F. Cronin
Jianfeng Guo
Kathleen A Fitzgerald
Meenakshi Malhotra
James C Evans

Subjects

Biochemistry

Topics
rna interference cancer cell lines gene silencing surface charge gene delivery prostate cancer disease models cancer cells

Formulation and Evaluation of Anisamide-Targeted Amphiphilic Cyclodextrin Nanoparticles To Promote Therapeutic Gene Silencing in a 3D Prostate Cancer Bone Metastases Model. (2017)

Abstract In recent years, RNA interference (RNAi) has emerged as a potential therapeutic offering the opportunity to treat a wide range of diseases, including prostate cancer. Modified cyclodextrins have emerged as effective gene delivery vectors in a range of disease models. The main objective of the current study was to formulate anisamide-targeted cyclodextrin nanoparticles to interact with the sigma receptor (overexpressed on the surface of prostate cancer cells). The inclusion of octaarginine in the nanoparticle optimized uptake and endosomal release of siRNA in two different prostate cancer cell lines (PC3 and DU145 cells). Resulting nanoparticles were less than 200 nm in size with a cationic surface charge (∼+20 mV). In sigma receptor-positive cell lines, the uptake of anisamide-targeted nanoparticles was reduced in the presence of the sigma receptor competitive ligand, haloperidol. When cells were transfected in 2D, the levels of PLK1 mRNA knockdown elicited by targeted versus untargeted nanoparticles tended to be greater but the differences were not statistically different. In contrast, when cells were grown on 3D scaffolds, recapitulating bone metastasis, targeted formulations showed significantly higher levels of PLK1 mRNA knockdown (46% for PC3 and 37% for DU145, p < 0.05). To our knowledge, this is the first time that a targeted cyclodextrin has been used to transfect prostate cancer cells in a 3D model of bone metastasis.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Caitriona M O' Driscoll, Raphael Darcy, Fergal J O'Brien, Caroline M Curtin, Michael F. Cronin, Jianfeng Guo, Kathleen A Fitzgerald, Meenakshi Malhotra, James C Evans

Experts in our system

1
Caitriona M O' Driscoll
University College Cork
Total Publications: 8
 
2
Raphael Darcy
University College Cork
Total Publications: 37
 
3
Fergal J O'Brien
Royal College of Surgeons in Ireland
Total Publications: 268
 
4
Caroline M Curtin
Royal College of Surgeons in Ireland
Total Publications: 22
 
5
Michael F. Cronin
University College Cork
Total Publications: 3
 
6
Jianfeng Guo
University College Cork
Total Publications: 27
 
7
Kathleen A Fitzgerald
University College Cork
Total Publications: 10
 
8
Meenakshi Malhotra
University College Cork
Total Publications: 14
 
9
James C Evans
University College Cork
Total Publications: 13