Nanocarrier-mediated intracellular protein delivery is a promising strategy for treatment of disease, but is hindered by limitations to chemical design space and endosomal entrapment of delivered protein cargo. We developed a robust polymeric-protein nanocomposite (PPNC) platform to achieve direct cytosolic protein delivery, as demonstrated by imaging flow imaging cytometry. We synthesized a library of semi-rigid homopolymers with varying molecular weights and cationic functionality to electrostatically bind to and deliver co-engineered proteins featuring anionic glutamate ‘E-tags’  to the cytosol of mammalian cells. These PPNC platforms demonstrated effective intracellular protein delivery for proteins of ranging size and charge, including an active therapeutic endonuclease (Cre recombinase) and a multimeric fluorescent protein (tdTomato). Higher molecular weight polymers demonstrate a larger range of effective formulations for protein delivery under serum conditions, making them robust agents for therapeutic protein delivery with potential for clinical translatability.

Rationally designed polymers for intracellular protein delivery

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.