title: Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells.
abstract: The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer.
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland. Electronic address: j.guo@ucc.ie.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Caitriona M
authors.initials: CM
authors.lastname: O'Driscoll
authors.affiliation: Materials Chemistry and Analysis Group, Department of Chemistry and The Tyndall National Institute, University College Cork, Cork, Ireland; Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Holmes
authors.affiliation: Materials Chemistry and Analysis Group, Department of Chemistry and The Tyndall National Institute, University College Cork, Cork, Ireland; Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, Dublin 2, Ireland; Department of Sciences, Faculty of Natural and Applied Science, Notre Dame University (Louaize), Zouk Mosbeh, Lebanon. Electronic address: kamil.rahme@ndu.edu.lb.
authors.forename: Kamil
authors.initials: K
authors.lastname: Rahme
mesh_terms: D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006046:Gold / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D006046:Gold; D005492:Folic Acid
keywords: Gold nanoparticles; Non-viral siRNA delivery; Prostate cancer gene therapy; Receptor-mediated internalisation; Targeting ligands