Research Areas: DNA Nanotechnology, Biopolymers, Targeted Drug & Gene Delivery, Hydrogels
The field of DNA nanotechnology has transformed DNA from a material that stores genetic information into a construction tool that can be used to build 3D scaffolds and devices with nanoscale features. There are a variety of strategies that can be used to create DNA nanostructures, each that use a combination of many different single stranded DNA (ssDNA) sequences that when mixed together and subjected to specific annealing conditions can produce double stranded DNA segments that organize into highly uniform structures of the desired shape. In our group we use a different approach where we start with a single hydrophilic ssDNA sequence and conjugate it to a hydrophobic tail to form an amphiphilic molecule. The amphiphilic nature of the conjugate induces spontaneous assembly of the molecules when added to an aqueous environment. Our ssDNA-amphiphiles, containing a random nucleic acid headgroup or an aptamer, can adopt a variety of self-assembled structures including twisted and helical bilayer nanotapes and nanotubes. The ability to create DNA nanotubes from ssDNA-amphiphiles is particularly exciting, and our goal is to design and engineer different nanotubes and other DNA nanostructures that will be used for targeted delivery of small molecules and nucleic acids to tissues of interest.
Multi-Targeted Gene & Drug Delivery
Currently, the main problems associated with systemic drug administration are the necessity of a large drug dose to achieve high local concentration, non-specific toxicity and other adverse side-effects due to high drug doses, even biodistribution throughout the body and lack of specific affinity for the pathological site. Targeted drug delivery can bring a solution to all these problems. Our goal is to engineer multi-targeted therapeutic systems that could aid recognition of the site of interest and delivery of the therapeutic load into a variety of target cells. Therefore, higher degree of specificity for cancer cells could be achieved by designing a modular multi-targeted non-viral system that introduces simultaneous targeting of multiple overexpressed cancer surface receptors as the first level of targeting at the extracellular level. Subsequently, transcriptional targeting is introduced as the second level of specific targeting. Our studies provide an insight into the mechanisms by which surface molecules, such as peptide-amphiphile ligands and polymers, modulate the non-viral nanoparticle behavior, and will contribute significantly to the rational design and engineering of gene and drug delivery systems with improved targeting functionality.
Thermosensitive and Biodegradable Hydrogels for Local Delivery of Therapeutics and Tissue Engineering
Hydrogels are 3D polymeric networks that swell in water or biological fluids. They are attractive biomaterials with broad applications in the fields of drug delivery, tissue engineering and biosensing. Although both chemical and physical hydrogels have been extensively studied for biomedical applications, physical hydrogels are particularly attractive due to in-situ gelation in response to physiological stimuli, such as temperature, pH, and ionic strength. We have designed a new polymer that shows a spherical-to-wormlike liquid-gel transition, is a liquid at room temperature and gels at physiological temperature in water or cell media, degrades in vitro in about 45 days in cell media, and has more favorable degradation properties (e.g., moderate biodegradation rate and slower pH drop during degradation) compared to other hydrogels. Taken together with its porous structure, this newly developed thermosensitive and biodegradable hydrogel is an attractive candidate for biomedical applications, so we are currently exploring this for the local delivery of targeted nanoparticles to cancer and as a scaffold for tissue engineering.