Emerging interest in research of polymeric biomaterials towards human health has intrigued me to pursue my graduate research, primarily towards a few biomedical applications like radiation dosimetry, drug & gene delivery systems. Although Radiotherapy remains a foundation of cancer treatment procedures in clinic; overdosing of radiation can induce toxicity to sensitive organs and underexposure can lead to low efficacies of tumor treatment. Commercial sensors consist of several intrinsic disadvantages due to their sensitivity to heat and light, long processing times, and high costs. For real-time dose detection, a novel colorimetric hydrogel sensor was developed with formation of maroon-colored gold nanoparticles (templated by a variety of surfactants and amino acids) within an agarose-based polymeric hydrogel, upon exposure of ionizing radiation. Translational potential of sensor was demonstrated using anthropomorphic phantoms and in live canine patients undergoing radiotherapy treatments by qualitatively and quantitatively measuring the delivered dose. Combination therapy by simultaneously using drug & gene delivery with a single multifunctional carrier can lead to novel treatment modalities for various diseases like Cancer, Alzheimer etc. A library of lipid-based Aminoglycoside-derived cationic self-assembling polymer nanoparticles (LPNs) was developed with size ranging from (50-150) nm. Lead LPNs showed great potential for concurrent delivery of nucleic acids along with small molecule drug such as histone deacetylase (HDAC) inhibitor, AR-42 as a combination treatment to cancer cells.

Over the past four decades, DNA nanotechnology has grown exponentially from a field focused on simple structures to one capable of synthesizing complex nano-machines capable of drug delivery, nano-robotics, digital data storage, logic gated circuitry, nano-photonics, and other applications. The construction of these nanostructures is possible because of the predictable and programmable Watson-Crick base pairing of DNA. However, there is an increasing need for the incorporation of chemical diversity and functionality into these nanostructures. To overcome this challenge, this work explored creating hybrid DNA nanostructures by making self-assembling small molecule/protein-DNA conjugates.In one direction, well studied host-guest interactions (i.e. cucurbituril[7]-adamantane) were used as the choice of self-assembling species. Binding studies using these small molecule-DNA conjugates were performed and thereafter they were used to assemble larger DNA origami nanostructures. Finally, a stimulus responsive DNA nano-box that opens and closes based on these interactions was also demonstrated. In another direction, a trimeric KDPG aldolase protein-DNA conjugate was probed as a structural building block by assembling it into a DNA origami tetrahedron with four cavities. This hybrid building block was thereafter characterized by single particle cryo-EM and the resulting electron density map was best fit by simulating origami cages with varying number of proteins (ranging from 0 to 4). Next, to increase access and for larger democratization of the field, an automation designer software tool capable of making DNA nanostructures was made. In this work, the focus was on making curved 3D DNA nanostructures. The last direction probed in this work was to make optical metamaterials based on complex 3D DNA architectures. Realization of a self-assembled 3D tetrastack geometry is still an unachieved dream in the field of DNA self-assembly. Thus, this direction was probed using DNA origami icosahedrons. Finally, the work covered in my thesis probes multiple directions for advancing DNA nanotechnology, both fundamentally and for potential applications.