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A gold nanoparticle platform for the delivery of functional microRNAs into cancer cells.

Biomaterials (2012-11-01)
Rajib Ghosh, Lalithya C Singh, Jason M Shohet, Preethi H Gunaratne
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cysteamine hydrochloride, ≥98% (titration)
Sigma-Aldrich
Cysteamine, ~95%
Sigma-Aldrich
Cysteamine, ≥98.0% (RT)
Sigma-Aldrich
Cysteamine hydrochloride, BioXtra
Sigma-Aldrich
Cysteamine hydrochloride, ≥97.0% (RT)