UC Berkeley

Nanoparticle formulations of chemotherapeutics have been shown to be highly effective in the treatment of various cancers by increasing the amount of drug that can be delivered, reducing systemic toxicity, and increasing tumor uptake. Many nanoparticle scaffolds have been investigated in a drug delivery context, displaying diverse sizes, morphologies, compositions, and properties. One class of nanoparticles that has shown promise for drug delivery applications are those based on self-assembling proteins. These protein-based nanoparticles share many of the advantages of more traditional nanoparticle scaffolds made from synthetic materials, but also benefit from being biodegradable and genetically tuneable. Herein, the development of a new class of self-assembling proteins based on an intrinsically disordered protein sequence derived from human neurofilaments is discussed. Efforts to systematically alter the sequence space of these proteins to study variables that impact their physicochemical and self-assembling properties were undertaken. This allowed for the identification of protein variants that had favorable characteristics as drug delivery scaffolds and as general bio-surfactants. This work represents the initial steps in developing a quantitative model for the future engineering of self-assembling proteins based on this intrinsically disordered protein sequence.