Modularized Gold Nanocarriers for TAT‐Mediated Delivery of siRNA

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.

A DNA–Azobenzene Nanopump Fueled by Upconversion Luminescence for Controllable Intracellular Drug Release

“…Endowing the DNA–azo nanopump with nuclear‐targeting capacity can avoid the impairment and suppress multidrug resistance . Thus, HIV‐1 TAT was assembled on the nanopump, which increased the hydrodynamic diameter (Supporting Information, Figures S3 d and S10 a) and Zeta potential (Supporting Information, Figure S10 c). After anionic HA was introduced through electrostatic adsorption for specifically targeting cancer cells, the resulting nanopump had a hydrodynamic diameter of 118.8 nm (Supporting Information, Figure S10 b) and a negative Zeta potential.…”

Light‐Triggered Genome Editing: Cre Recombinase Mediated Gene Editing with Near‐Infrared Light

“…First, a 5′ thiol–DNA sequence terminated with a 3′ amine is assembled onto the particle surface by low pH induced adsorption . A complementary DNA strand is hybridized to the anchoring DNA strand to allow for a rigid assembly point for further functionalization and for high‐efficiency release . The 3′ amines of the anchoring strands are functionalized with a thiol–nitrilotriacetic acid (NTA) derivative by the bifunctional cross‐linker, N‐hydroxysuccinimide‐polyethylene glycol 4 ‐maleimide (NHS‐PEG 4 ‐maleimide).…”

Near Infrared-Triggered Liposome Cages for Rapid, Localized Small Molecule Delivery

“…In the following nanoseconds, however, the HGN dissipates its thermal energy by vaporizing a minute amount of water, nucleating transient nanobubbles around the HGN [19][20][21][23][24][25][26][27][28][29] .The nanobubbles rapidly expand and collapse, similar to cavitation bubbles formed by ultrasound 19 , without significantly changing the bulk liquid temperature. The mechanical forces caused by the growth and collapse of the nanobubbles ruptures the adjacent liposome membrane, and the cargo is jettisoned from the liposome with micron spatial resolution and millisecond time resolution 12,13,19,20,[30][31][32][33] . Triggered release can be accomplished within individual cells following endocytosis of liposome-HGN with sub-cell level resolution 12,13,[30][31][32][33][34] .…”