Modularized Gold Nanocarriers for TAT‐Mediated Delivery of siRNA. Issue 8 (18th November 2016)

• Record Type: Journal Article
• Authors: Huang, Xiao; Lai, Yifan; Braun, Gary B.; Reich, Norbert O.
• Is Part Of: Small. Volume 13:Issue 8(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-11-18
• Subjects: gold nanocarriers -- siRNA -- streptavidin -- TAT peptides; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201602473
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract : Targeted delivery of siRNA controlled by near‐infrared light using hollow gold nanoshells has been demonstrated in cancer and stem cells models. Here, a universal surface module and several functionalization rules for the maximized delivery of short nucleic acids (here, siRNA) applicable for diverse gold nanocarriers are described. Streptavidin is devised as a handle to assemble biotinylated cell penetrating peptides (e.g., transactivating transcriptional activator (TAT)), as well as an insulator between the positive charge of TAT and the dense negative charge of RNA. However, direct linking of streptavidin to functional siRNA inhibits its silencing activity. The approach then involves the orthogonal assembly of two types of RNA strands: one with biotin modification for cell targeting and penetration (scaffold RNA); the other without biotin as functional RNA (i.e., siRNA). Initially, flexible single‐stranded RNA is used for dense surface‐packing, followed by hybridization with the complementary RNA strand to maximize the assembly of the targeting peptide for cellular uptake and siRNA delivery. This orthogonal approach for the delivery of short oligonucleotides, together with novel surface functionalization rules discovered here, should enable the use of these materials for nanomedicinal research and applications. Abstract : A modular RNA scaffold is designed on gold nanocarriers for efficient functional RNA delivery in diverse mammalian cells. The universal biotin‐modified RNA strands are densely loaded on surface, and hybridized with RNA to maximize the amount of streptavidin for transactivating transcriptional activator (TAT) peptide coating and cell penetrating. Functional RNA strands of interest are assembled orthogonally with scaffold RNA at an optimal ratio.