Peroxidase-Mediated In Situ Fabrication of Multi-Stimuli-Responsive and Dynamic Protein Nanogels from Tyrosine-Conjugated Biodynamer and Ovablumin

Horseradish peroxidase (HRP)-mediated oxidation of tyrosine-conjugated biodynamer containing acylhydrazone linkages and ovalbumin (OVA)/reduced ovalbumin (rOVA) generated protein nanogels through simultaneous tyrosine coupling and thiol cross-linking in the presence of H₂O₂. The obtained nanogels are multi-stimuli-responsive to temperature, pH, and glutathione (GSH) and possess the dynamic character of reversible covalent bonds. The OVA-based or rOVA-based protein nanogels can be utilized as cargoes of anticancer drug curcumin (Cur). The Cur-loaded protein nanogels rapidly released Cur in intracellular-mimicking acidic and reductive environment, thus, making these protein nanogels promising nanocarriers for intracellular drug delivery. HRP-mediated cross-linking of the tyrosine-conjugated biodynamer and proteins provides a facile and versatile approach for fabrication of responsive and adaptive biohybrid nanogels under mild conditions.