Karina Kizjakina

Ph.D. Candidate

Virginia Tech

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Education: B.S. - Chemistry, University of Latvia, Riga, Latvia (2005)

Currently working towards Ph.D. in Organic/Polymer Chemistry (expected Fall 2010)

karina kizjakina cv-updated 8.13.2010.pdf

Projects:

The delivery of nucleic acids at the tissue and cellular levels still remains one of the major hurdles in this scientific area. Since nucleic acids are bulky macromolecules and unstable in the presence of nucleases, vehicles are required to compact them into nanosized particles, offer protection from degradation in vivo, and release the therapeutic cargo at the desired location. Polycationic vehicles are good candidates for these purposes since they can be chemically modified to tune the desired properties in nanoparticle formulations.

We designed families of carbohydrate/oligoamine copolymers which showed promising plasmid DNA (pDNA) transfection results in the presence of serum proteins. Trehalose, beta-cyclodextrin, or maltose moieties were copolymerized with linear oligoethyleneamines of varying length via stepgrowth Cu(I)-catalyzed azide-alkyne cycloadditon polymerization resulting in series of copolymers with different carbohydrates and a range of secondary amines (from 4 to 6) within the polymer backbone. Upon electrostatic complexation of the polycations and pDNA in aqueous media, nanosized particles were formed, and their sizes and zeta-potentials were characterized via dynamic light scattering (DLS). The glycopolymers were tested for pDNA binding, toxicity, cellular uptake, and transfection efficiency in vitro. Characterization of these polymers revealed a significant influence of minor structural modifications on bioactivity. In general, all of the polymers efficiently bind pDNA at low nitrogen to phosphate (N/P) ratios forming nanoparticles of 100-200 nm in size and demonstrated cellular uptake and transfection. Polymers comprised at trehalose moieties and four secondary amines in the repeat unit showed the greatest promise in pDNA delivery in vitro. Due to its large hydration volume, we hypothesize that trehalose contributes to particle stabilization in serum. These trehalose-based polymers with four secondary amines were subsequently modified with PEG (5kDa). This modification is leading to the development of well-defined polymeric structures with PEG moieties selectively incorporated at the ends of linear trehalose/oligoethyleneamine polycations. The study of the effect of this modification on bioactivity is still in progress.