Helen Chen began her undergraduate research working on alternative, efficient sources of light. From there she moved on to a focus on novel methods of drug delivery, an area of high interest to pharmaceutical companies. Helen has found that her research experience, with its numerous failed experiments leading to a few successes, has helped her develop patience, persistence and optimism. She further demonstrated her passion for research by serving on the UROP Student Editorial Board, assisting with the publication of the 2007 UCI Undergraduate Research Journal. Helen is currently attending graduate school.

Most drugs are delivered in the body non-specifically and can act on healthy cells, potentially triggering side effects. The targeting of drug molecules to specific cells to reduce side effects has become the main aim of targeted therapeutics; however, the design of nanoscale drug delivery vehicles remains a challenge. One aspect of this design is the ability to hold and transport pharmaceutically-active molecules. To this end, we developed a protein assembly that can form complexes with drug molecules and essentially house them. The protein assembly is based on the E2 component of pyruvate dehydrogenase from Bacillus stearothermophilus. It forms a dodecahedral complex with twelve openings, each 5 nm in diameter, through which small molecules can diffuse. The hollow internal cavity gives the protein scaffold the ability to encapsulate molecules. Genetic modification of the cavity yields a scaffold with 60 cysteine thiol groups available for covalent linkage with guest molecules. Two different fluorescent dye molecules were used as model drugs to assess the reactivity of the thiol side chains. As expected, the cysteine mutant selectively reacted with the maleimide molecules, but not in reactions with the wild-type control. Our results demonstrate the ability of the engineered protein scaffold to encapsulate foreign molecules within its internal cavity and to potentially serve as a drug delivery vehicle.

Szu-Wen Wang Henry Samueli School of Engineering

The delivery of drug molecules to only their intended site of therapy has been a goal in the treatment of diseases but has not yet been fully realized. Such fine control over biodistribution would maximize the efficacy of treatment and minimize side effects. Nanoparticles have been investigated as vehicles for drug delivery, as they exhibit advantageous characteristics for targeting tumor cells. The challenges of traditional nanoparticles, however, are that the required size, size distribution, and chemical functionalization are difficult to achieve. Natural protein scaffolds that form hollow particles can address these issues. In this paper, Helen Chen has shown that the first major requirement, the encapsulation of drug molecules, is achievable. This opens up the possibility of using these scaffolds in therapeutic targeting.