A goal of materials research is to make responsive, biocompatible materials that can respond uniquely to environmental conditions and also be targeted to specific sites in the body. The development of carriers that can specifically target sites of disease would increase the efficacy of treatments and reduce toxic side effects of drugs delivered systemically. Nano-materials, such as spherical micelles and vesicles, can be used to carry large payloads of drugs and imaging agents. For all of the promise of targeted drug delivery, there are relatively nanomaterials that afford robust, targeted delivery while being responsive to environmental conditions. To meet this significant need, the PI's goal is to make a class of nanocarriers, made from a naturally occurring plant protein called oleosin, that can target specific sites, be turned on for drug delivery only in specific locations, and have reduced immunogenicity. The PI will introduce responsive domains into the protein using recombinant biotechnology, and demonstrate how carriers made of the protein can bind to sites of inflammation using a flow chamber lined with endothelial cells, the cells which line blood vessels. This work will also impact the lives of students who are trained in the PI's laboratory. The graduate students who work on this project will be trained in the most current techniques in materials science, and be prepared for careers in scientific research. In addition, the PI will continue to run a highly successful summer program to introduce and encourage talented high school students to pursue careers in science and engineering.
This award by the Biomaterials program in the Division of Materials Research to University of Pennsylvania is to engineer an amphiphilic plant protein, oleosin, to make targeted, responsive nanocarriers for drug delivery and imaging. Because oleosin is made recombinantly, we can embed designer functionality within these vesicles using the tools of molecular biology. The resulting investigation will lead to a new class of responsive, bio-inspired materials with enormous flexibility for targeted delivery. The PI hypothesize that large stretches of oleosin can be replaced with domains from other proteins, preserving the amphilicity and self-assembly of the molecules, but allowing the design of new materials. One strategy will be to embed protease cleavable domains into materials that allow for environmental proteases to trigger the binding of nano-materials, or the release of drugs they are carrying after binding. A second strategy will be to incorporate domains from human intrinsically disordered proteins into oleosin, which will allow us to make humanized oleosins. The PI will study how the length, number and type of IDP affects the assembly of the nanocarrier and reduces its immunogenicity. The PI will demonstrate how these materials can be used to deliver drugs specifically to inflammatory sites using activated endothelial cells in a flow chamber, targeting the endothelial surface molecule E-selectin. In the process, graduate students will be educate in cutting edge methods for making and testing the activity of recombinant proteins, and introduce high school students to research at the university level and encourage them to pursue careers in science and engineering.