Matthew V. Tirrell Interview
Sandeep Ravindran; PNAS December 28, 2021 118 (52) e2120415118
.png)
Figure: Matthew V. Tirrell. Image credit: University of Chicago, Chicago, IL.
Matthew V. Tirrell has been at the forefront of efforts to understand and apply the surface and interfacial properties of organic polymers and micellar nanoparticles. His contributions to the field led to his election to the National Academy of Sciences in 2019. Now dean of the Pritzker School of Molecular Engineering at the University of Chicago and a senior scientist at the Argonne National Laboratory, Tirrell has unraveled phase separation in polymers and nanoparticles and helped design and synthesize novel self-assembling materials with targeting and therapeutic potential. In his Inaugural Article, Tirrell describes self-assembling micelle nanoparticles that can target atherosclerotic plaques and deliver packaged nucleic acids to the plaques as potential treatments.
How did you first become interested in using nanoparticles to target atherosclerotic plaques?
Tirrell:More than a decade ago, when I was at the University of California, Santa Barbara, I made the acquaintance of a well-known scientist named Erkki Ruoslahti. He had been developing methods for phage-display discovery of targeting peptides, and we started focusing on this one peptide that homed in to blood clots. We published a couple of papers using the peptide that Erkki had discovered, placed into constructs we developed that at the time we called peptide amphiphiles. These were conjugate molecules, where a peptide is coupled to a hydrophobic tail with a polyethylene glycol spacer in between. The hydrophobic tails come together and make a well-defined spherical micelle with about a hundred molecules [and] a very high multivalent display of these targeting peptides on the outside of the micelle. We showed that a particle like this could be injected into the tail vein of a mouse and find pathological tissue that had blood clots on it. These tissues can be tumors, because tumors have leaky blood vessels, or they could be atherosclerotic plaques, because so-called vulnerable or unstable plaques that might be prone to rupture typically have microclots and microfractures on their surface.
Views: 196