All-natural gelatin-based bioorthogonal catalysts for efficient eradication of bacterial biofilms

Bioorthogonal catalysis mediated by transition metal catalysts (TMCs) presents a versatile tool for in situ generation of diagnostic and therapeutic agents. The use of ‘naked’ TMCs in complex media faces numerous obstacles arising from catalyst deactivation and poor water solubility. The integration of TMCs into engineered inorganic scaffolds provides ‘nanozymes’ with enhanced water solubility and stability, offering potential applications in biomedicine. However, the clinical translation of nanozymes remains challenging due to their side effects including the genotoxicity of heavy metal catalysts and unwanted tissue accumulation of the non-biodegradable nanomaterials used as scaffolds. We report here the creation of an all-natural catalytic “polyzyme”, comprised of gelatin–eugenol nanoemulsion engineered to encapsulate catalytically active hemin, a non-toxic iron porphyrin. These polyzymes penetrate biofilms and eradicate mature bacterial biofilms through bioorthogonal activation of a pro-antibiotic, providing a highly biocompatible platform for antimicrobial therapeutics.