Nathan P. Gabrielson

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We previously reported that gene delivery efficiency of 25-kDa, branched polyethylenimine (PEI) increased upon acetylation of up to 43% of the primary amines with acetic anhydride. In the present work, we investigated the effects of further increasing the degree of acetylation and elucidated the source of the higher gene delivery efficiency. Despite reduced(More)
This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface(More)
Most in vivo gene therapies will require cell-specific targeting. Although vector targeting through ligand attachment has met with success in generating gene delivery particles that are capable of specific cellular interactions, little attention has been given to the possible effects of such ligands on subsequent intracellular processing. In this study, we(More)
Novel gene delivery agents based on combining cholesterol units with spermine-functionalised dendrons exhibit enhanced transfection ability-we report significant synergistic effects in mixed (hybrid) systems which combine aspects of both main classes of synthetic vectors, i.e., cationic polymers and lipids.
This paper develops a structure-activity relationship understanding of the way in which surfactant-like dendrons with hydrophilic spermine surface groups and a variety of lipophilic units at their focal points can self-assemble and subsequently bind to DNA with high affinity. The choice of functional group at the focal point of the dendron and the high(More)
Polypeptides were the first set of materials considered for use as nonviral gene delivery vectors. With its ability to bind and condense anionic plasmid DNA, cationic poly-l-lysine (PLL) was one of the most well studied of the early gene delivery polypeptides. Unfortunately, as a DNA delivery vector, unmodified PLL suffered from low transfection efficiency.(More)
Research interest in chitosan stems in part from the demonstrated wound healing properties. The benefits of chitosan as a therapeutic agent appear to be paradoxical because chitosan also elicits neutrophil infiltration indicative of an inflammatory response. While the affinity between chitosan and neutrophils has been well documented, the underlying(More)
Nonviral gene delivery with synthetic cationic polymeric vectors is widely recognized as an attractive alternative to viral gene delivery, which suffers from inherent immunogenicity and various side effects. The transfection efficiency and chemotoxicity of these polymeric vectors are often closely related to the density of their cationic charge. Materials(More)
Many human gene therapies will require cell-specific targeting. Though recombinant viruses are much more efficient than nonviral vectors, the latter, especially polymers, have the advantage of being targetable via conjugation of cell-specific ligands, including sugars, peptides, and antibodies, which can be covalently attached to the polymer using a variety(More)
Small molecule chemotherapeutics often have undesired physiochemical and pharmacological properties, such as low solubility, severe side effect and narrow therapeutic index. To address these challenges, polymeric nanomedicine drug delivery technology has been routinely employed, in particular with the use of biodegradable and biocompatible polyesters, such(More)