title: A gold nanoparticle platform for the delivery of functional microRNAs into cancer cells.
abstract: Lack of affordable technologies for delivering microRNAs and siRNAs into cells on a large scale has hindered our efforts to rapidly parse through hundreds of dysregulated genes/microRNAs in order to identify drivers of complex diseases. The instability and polyanionic nature of naked microRNAs impede efficient cellular uptake and reduce half-life. Viral delivery requires cloning, microRNA mimics/inhibitors require costly modifications, and both require toxic lipofection or electroporation. To address these challenges, we developed a robust method for delivering unmodified microRNAs into cells on cysteamine-functionalized gold nanoparticles (AuNPs). We validated our method in two different tumor models and found that the best formulation of miR(1)-AuNP(10)-S-PEG(0.5) had the highest payload (10-20 fold higher than lipofection), lowest toxicity (98% of cell viability following treatment), efficient uptake (96% of cells took it), fastest endosomal escape and increased half-lives (at least 5 days) impacting cell proliferation and patterns of target gene expression.
authors.affiliation: Department of Biology & Biochemistry, University of Houston, 4800 Calhoun Road, Houston, TX 77204, USA.
authors.forename: Rajib
authors.initials: R
authors.lastname: Ghosh
authors.forename: Lalithya C
authors.initials: LC
authors.lastname: Singh
authors.forename: Jason M
authors.initials: JM
authors.lastname: Shohet
authors.forename: Preethi H
authors.initials: PH
authors.lastname: Gunaratne
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D003543:Cysteamine / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006046:Gold / Q000737:chemistry*; D006801:Humans; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D003543:Cysteamine; D006046:Gold