In vivo disassembly of IV administered siRNA matrix nanoparticles at the renal filtration barrier.

Intravenous administration of siRNA nanocarriers may provide unique therapeutic opportunities for tissue-specific gene silencing. Although often engineered to overcome the numerous barriers that exist in the systemic circulation, many nanocarriers fail in extending the circulation time of the siRNA. A more detailed assessment of the different clearance mechanisms that are in play after intravenous injection could therefore be of value to improve siRNA nanocarrier design.

Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression.

Purpose: Tumor necrosis factor α (TNF-α) plays a key role in the progression of rheumatoid arthritis and is an important target for anti-rheumatic therapies. TNF-α expression can be silenced with small interfering RNA (siRNA), but efficacy is dependent on efficient and safe siRNA delivery vehicles. We aimed to identify polymeric nanocarriers for anti-TNF-α siRNA with optimal efficacy and minimal off-target effects in vitro.

Hemocompatibility of siRNA loaded dextran nanogels.

Although the behavior of nanoscopic delivery systems in blood is an important parameter when contemplating their intravenous injection, this aspect is often poorly investigated when advancing from in vitro to in vivo experiments. In this paper, the behavior of siRNA loaded dextran nanogels in human plasma and blood is examined using fluorescence fluctuation spectroscopy, platelet aggregometry, flow cytometry and single particle tracking. Our results show that, in contrast to their negatively charged counterparts, positively charged siRNA loaded dextran nanogels cause platelet aggregation and show increased binding to human blood cells.

Advanced fluorescence microscopy methods illuminate the transfection pathway of nucleic acid nanoparticles.

A great deal of attention in biopharmacy and pharmaceutical technology is going to the development of nanoscopic particles to efficiently deliver nucleic acids to target cells. Despite the great potential of nucleic acids for treatment of various diseases, progress in the field is fairly slow. One of the causes is that development of suitable nanoscopic delivery vehicles is hampered by insufficient knowledge of their physicochemical and biophysical properties during the various phases of the transfection process.