Structure-Dependent Biodistribution of Liposomal Spherical Nucleic Acids.

Spherical nucleic acids (SNAs) are a class of nanomaterials with a structure defined by a radial distribution of densely packed, short DNA or RNA sequences around a nanoparticle core. This structure allows SNAs to rapidly enter mammalian cells, protects the displayed oligonucleotides from nuclease degradation, and enables co-delivery of other drug cargoes. Here, we investigate the biodistribution of liposomal spherical nucleic acid (LSNA) conjugates, SNA architectures formed from liposome templates and DNA modified with hydrophobic end groups (tails).

Impact of Sequence Specificity of Spherical Nucleic Acids on Macrophage Activation in Vitro and in Vivo.

The effects of spherical nucleic acid (SNA) gold nanoparticle conjugates on the activation of macrophages in vitro and release of cytokines in vivo were explored. Herein, we show that G-quadruplexes, the formation of which is enhanced on gold nanoparticle surfaces, elicit an increase in cytokine release from mouse and human macrophages and induce the upregulation of activation receptors as well as NO production in vitro. Moreover, these G-rich SNAs can induce cytokine release when injected intravenously, though there were no severe, long-term effects observed.

Dual Toll-Like Receptor Targeting Liposomal Spherical Nucleic Acids.

Liposomal spherical nucleic acids (LSNAs) are a class of nanomaterial used broadly for biomedical applications. Their intrinsic capacity to rapidly enter cells and engage cell surface and intracellular ligands stems from their unique three-dimensional architecture, which consists of densely packed and uniformly oriented oligonucleotides on the surface of a liposomal core. Such structures are promising for therapeutics because they can carry chemical cargo within the lipid core in addition to the nucleic acids that define them, in principle enabling delivery of multiple signals to a single cell.

Relationships between Poly(ethylene glycol) Modifications on RNA-Spherical Nucleic Acid Conjugates and Cellular Uptake and Circulation Time.

Two synthetic approaches that allow one to control PEG content within spherical nucleic acids (SNAs) have been developed. One approach begins with RNA-modified gold nanoparticles followed by a backfill of PEG 2K alkanethiols, and the other involves co-adsorption of the two entities on a gold nanoparticle template. These two methods have been used to explore the role of PEG density on the chemical and biological properties of RNA-SNAs.

New Tools in Experimental Cellular Therapy for the Treatment of Liver Diseases.

The current standard of care for end stage liver disease is orthotopic liver transplantation (OLT). Through improvement in surgical techniques, immunosuppression, and general medical care, liver transplantation has become an effective treatment over the course of the last half-century. Unfortunately, due to the limited availability of donor organs, there is a finite limit to the number of patients who will benefit from this therapy.