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Ilya Zharov

Associate Professor of Chemistry

Diploma Chelyabinsk State University, Russia

Ph.D. University of Colorado, Boulder

Research

References

zharov@chem.utah.edu

Ilya Zharov's Lab Page

Ilya Zharov's PubMed Literature Search

Research

Our work related to biological chemistry is conducted in two main areas. The focus of the first area is on biomimetic nanopores. In particular, we work on the preparation and study of nanoporous colloidal materials. Synthetic colloidal crystals form via self-assembly of nanoscale-sized silica spheres into a close-packed face-centered cubic lattice and contain highly ordered arrays of three-dimensional interconnected pores 5-100 nm in size (Figure 1). We use nanoporous colloidal films, membranes and microfluidic channels for size-selective transport of drug molecules and biomacromolecules. Furthermore, we modify the surface of colloidal nanopores with organic moieties that can non-covalently interact with ions and molecules, and whose charge and shape respond to external stimuli, such as pH or light. As a result of the surface modification, we are able to control molecular transport through the colloidal nanopores, either by tuning the nature and strength of the non-covalent interactions or by changing the environmental conditions. We study the transport of small molecules and biomacromolecules through unmodified and surface-modified colloidal membranes. By using films and membranes possessing well defined nanopores, we are able to quantitatively analyze the molecular transport rate as a function of pore size, surface modification and environmental conditions. These studies provide mechanistic insights and allow achieving a fine control of molecular transport through the nanopores.

In the second research area we are working on two designs of modular macromolecular anti-cancer agents that will utilize boron neutron capture (BNC) as a cancer-fighting method. First, we prepare dendritic integrin antagonists. We are designing conjugates of synthetic integrin ligands with neutron capture functionality to allow highly selective targeting of the tumor neovasculature. Our modular approach, outlined in Figure 2, offers a high degree of structural flexibility and potential for rapid modification of each individual module. It simplifies the optimization of binding properties and bioavailability of the designed molecular antagonists without significant additional synthetic effort. We are using monomeric avb3-selective integrin ligands as the targeting module and fluorescent dyes as the imaging module. At the moment we are focusing on the preparation of ester-based dendrons carrying neutral, anionic and metal-coordinated carboranyl clusters. We plan to develop efficient convergent coupling strategies that will allow rapid conjugation of the designed dendritic modules into macromolecular agents. Synthesis of a macromolecular agent from the individual modules will require orthogonal protection of the functional groups to maximize yields of the desired product. In the future we will evaluate the affinity and specificity of the agents toward surface-immobilized integrins. Endothelial cell migration and proliferation assays will be used to evaluate the efficacy of the designed agents. Cellular localization/distribution will be evaluated by laser-scanning confocal microscopy. Functional testing of the pro-apoptotic activity of the macromolecular agents after neutron capture will be conducted at the Lujan Neutron Science Center at Los Alamos National Laboratory. Secondly, we work on the preparation of nanoparticle BNC materials. In this design we use dye-impregnated silica nanoparticles carrying boron-containing polymer brushes on their surface, or silica nanoparticles containing boron atoms as a part of the nanoparticle oxide structure. Both types of nanoparticles are capped with integrin ligands. This design combines the advantages of the modular approach with the ability to introduce a larger number of boron atoms and additional ease of materials preparation.

Figure 1: SEM images of the chemically-modified colloidal film prepared from 440 nm diameter silica spheres (A) top view, the geometric projection of a pore observed from the (111) plane is outlined in the inset. (B) Side view.

Figure 2: Schematic representation of a modular macromolecular antagonist incorporating integrin recognition functionality, fluorescent tag, and carboranyl moiety for Boron Neutron Capture.

 

References