Journal
BIOMATERIALS
Volume 34, Issue 3, Pages 807-816Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.10.023
Keywords
miRNA delivery; In vitro delivery; Gold nanoparticles; Cysteamine-funtionalized; Cancer
Funding
- Cancer Prevention Research Institute of Texas (CPRIT) [RP110355]
- Alliance for Nanohealth (ANH) [98436-104014]
- Cullen Foundation
- McNair Foundation
- Virginia & L.E. Simmons Family Foundation
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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)-AuNP10-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. (c) 2012 Elsevier Ltd. All rights reserved.
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