Engineered Lipid Coronas for Gold Nanoparticle-Based Bioorthogonal Catalysis

Abstract

Bioorthogonal catalysis provides a powerful biomedical tool for controlled ‘turn-on’ activation of prodrugs and pro-dyes. Gold-based catalysts are highly selective and nontoxic

however, they are susceptible to deactivation by serum proteins and biogenic thiols. We present here a strategy that protects gold nanoparticle (AuNP) catalysts with a lipid corona, enabling bioorthogonal catalysis in biological environments. The modular nature of the lipid corona enables tuning of the surface charge, membrane fluidity, and PEG content. The stability and activity of these lipid-coated AuNPs was demonstrated by successfully converting inactive propargylated doxorubicin to the active drug in cancer cells. © 2025 American Chemical Society.