Characterization of biomolecular nanoconjugates by high-throughput delivery and spectroscopic difference.

Robert K Delong, Azure Risor, Masaaki Kanomata, Amanda Laymon, Brooke Jones, Scott D Zimmerman, Joseph Williams, Colette Witkowski, Mathew Warner, Michael Ruff, Richard Garrad, John K Fallon, Anthony J Hickey, Reza Sedaghat-Herati

Index: Nanomedicine (Lond.) 7(12) , 1851-62, (2012)

Full Text: HTML

Abstract

Nanoparticle conjugates have the potential for delivering siRNA, splice-shifting oligomers or nucleic acid vaccines, and can be applicable to anticancer therapeutics. This article compares tripartite conjugates with gold nanoparticles or synthetic methoxypoly(ethylene glycol)-block-polyamidoamine dendrimers.Interactions with model liposomes of a 1:1 molar ratio of tripalmitin:cholesterol or phospholipid:cholesterol were investigated by high-throughput absorbance, as well as fluorescence difference and cellular luminescence assays.Spectral differences and dynamic light-scattering spectroscopy shifts demonstrated the interaction of conjugates with liposomes. Biological activity was demonstrated by upregulation of gene expression via splice-shifting oligomers, delivery of anti-B-Raf siRNA in cultured human cancer cells or tuberculosis antigen 85B plasmid expression vector in a coculture model of antigen presentation.The data suggests that gold nanoparticles and methoxypoly(ethylene glycol)-block-polyamidoamine dendrimer nanoconjugates may have potential for binding, stabilization and delivery of splice-shifting oligomers, siRNA and nucleic acid vaccines for preclinical trials.