Degradable polymer-coated gold nanoparticles for co-delivery of DNA and siRNA

Abstract

Gold nanoparticles have utility for in vitro, ex vivo, and in vivo imaging applications as well as for serving as a scaffold for therapeutic delivery and theranostic applications. Starting with gold nanoparticles as a core, layer-by-layer degradable polymer coatings enable co-delivery of both DNA and short interfering RNA simultaneously. To engineer release kinetics, polymers which degrade through two different mechanisms can be utilized to construct hybrid inorganic/polymeric particles. During fabrication of the nanoparticles, the zeta potential reverses upon the addition of each oppositely charged polyelectrolyte layer and the final nanoparticle size reaches approximately 200 nm in diameter. When the hybrid gold/polymer/nucleic acid nanoparticles are added to human primary brain cancer cells in vitro, they are internalizable by cells and reach the cytoplasm and nucleus as visualized by transmission electron microscopy and observed through exogenous gene expression. This nanoparticle delivery leads to both exogenous DNA expression and siRNA-mediated knockdown, with the knockdown efficacy superior to that of Lipofectamine® 2000, a commercially available transfection reagent. These gold/polymer/nucleic acid hybrid nanoparticles are an enabling theranostic platform technology capable of delivering combinations of genetic therapies to human cells.

Folate-decorated hydrophilic three-arm star-block terpolymer as a novel nanovehicle for targeted co-delivery of doxorubicin and Bcl-2 siRNA in breast cancer therapy

“…TEM is an effective means for observing the intracellular distribution of nanoparticles [56]. were mostly localized in the region near the nucleus, and a few was found in the nucleus ( Fig.…”

Biomimetic gold nanocomplexes for gene knockdown: Will gold deliver dividends for small interfering RNA nanomedicines?

“…Layer-by-layer (LbL) assembly is a prominent method of AuNP formulation for siRNA delivery in which multi-layered films with tailored properties can be fabricated on substrates [124]. This method has been used to prepare AuNPs with multi-layered shells through particle templating [125].…”

Gold nanoparticles for cancer theranostics — A brief update

“…43 It also demonstrated that NPs smaller than 10 nm could enter the nucleus for intranuclear delivery and therapy, whereas larger ones were found only in the cytoplasm. Although all kinds of polymer-coated AuNPs have been developed to load more nucleotides or to deliver combinations of genetic therapies to cancer cells, 44 there are still rare examples of using AuNPs-oligonucleotides conjugates for gene theranostics in vivo. It is partly because of instability of nucleic acid, especially for RNA.…”