Research Seminar –

Abstract: Bottlebrush polymer prodrugs are an important emerging class of synthetic macromolecules for biomedical applications such as gene and drug delivery. Currently, there exists a lack in understanding of how bottlebrush polymer prodrugs interact with proteins in biological media. It is known that when foreign particles (such as synthetic macromolecules) of a particular size are introduced into blood serum proteins rapidly accumulate onto their surfaces forming a “protein corona.” Importantly, the formation of protein coronas around foreign particles ultimately changes their intended biological identity and effects biodistribution, pharmacokinetics, cell uptake, etc. As such, it is important to understand how to control protein corona formation especially for synthetic macromolecules designed for gene and drug delivery. Standard approaches for protein corona characterization are not viable for small (~10 nm) macromolecules such as bottlebrush polymer prodrugs nor are they suited for elucidating the dynamics of protein corona formation over short durations of time. This lack of technology and gap in understanding poses a critical barrier in advancing the efficacy of bottlebrush polymer prodrugs. In the proposed work, an emerging technology (MicroMapping) in photocatalyzed proximity labeling will be leveraged to realize the first example of time-resolved and in situ characterization of molecular bottlebrush polymer protein coronas. Overall, this work will introduce a new tool for characterizing the protein coronas of small nanoparticles, provide the first protein corona map of molecular bottlebrush polymers, and significantly augment the clinical translation of bottlebrush polymer prodrugs.