MSE PhD Prospectus Defense: Haoyi Hou

MSE PhD Prospectus Defense: Haoyi Hou

TITLE: Molecular Self Assembly and Drug Delivery

ADVISOR: Arturo Vegas (Chemistry)

COMMITTEE: Mark Grinstaff (BME, MSE, Chemistry); Pinghua Liu (Chemistry); Joerg Werner (ME, MSE)

ABSTRACT: Self-assembly materials are composed of molecules that spontaneously organize into ordered structures without external guidance, often mimicking biological systems. However, self-assembly drug delivery systems often face the challenge of drug loading, controlled release, and targeting specification. Inspired by protein structure, the assembly and sequence of the composited amino acids can impact their secondary and tertiary structure, which further results in different properties. We assume the same strategy can be applied to integrate the functionality of the polymeric building blocks. Here, we applied a synthetic strategy to construct block polymers with pre-programmed drug delivery kinetics and developed a quantification tool for the biodistribution of targeting ligand and delivery vehicle. This Prospectus summarizes the synthesis and characterization of a degradable amphiphilic diblock hydrogel. The strategy towards controlling the degradation kinetics and the microstructural-functional relationship was examined. And the control of nanostructure was achieved through the implementation of a tertiary polymeric block. This block polymeric hydrogel showed the capability of cell delivery with preprogrammed degradation kinetics, and the nanoparticle system showed increased small molecule drug loading capacity and controlled release. This Prospectus also details a metal-encoded method to track the biodistribution of drug delivery material. A lanthanide metal-based complex was first conjugated with a small molecule targeting ligand using a single-strand DNA linker. And the quantification methods were tested and validated in vitro by comparing with FDA-approved targeting molecules. Then, an analog of this approach was further developed and applied for the discovery of lipid nanoparticles for agrichemical delivery.