A Minimal Hemin-Albumin Nanozyme with Peroxidase-like Activity Enabling Tyrosine-Crosslinked Hydrogel Formation
Abstract
Heme enzymes catalyze key oxidative reactions, yet their use in biotechnology is often limited by high production costs, low stability, and intricate operational conditions. Hemin, the catalytic iron-porphyrin cofactor of heme enzymes, has been explored as an alternative. However, its practical use is limited by its aggregation and deactivation in aqueous media. Here, we report a minimal biomimetic nanozyme based on the stabilization of hemin with bovine serum albumin (BSA) to enable aqueous catalysis and hydrogel formation under mild aqueous conditions. Through alkaline-mediated synthesis, hemin was stabilized with BSA, allowing the generation of a Hemin@BSA noncovalent hybrid with peroxidase- and catalase-like activity, outperforming free hemin or BSA complexed with hemin prepared under physiological conditions. Beyond standard peroxidase assays, Hemin@BSA catalyzed the oxidative C–C coupling of N-acetyl-tyrosine (NAT), yielding dityrosine as the main product. This enzymatic-like property was successfully applied at the macromolecular level, enabling the crosslinking of hyaluronic acid-tyramine (HA-TyrA) conjugates, yielding the formation of hydrogel networks with mechanical properties comparable to HRP-mediated crosslinked hydrogels. The cytotoxicity of hemin and Hemin@BSA was evaluated in both U87 glioblastoma and normal human astrocytes (NHA) cells, while cellular uptake and reactive oxygen species (ROS) generation were investigated in U87 cells, demonstrating efficient cellular uptake of Hemin@BSA and higher ROS levels induced by free hemin compared with Hemin@BSA. Overall, simple heme-protein complexes lie as the interface between molecular catalysts and functional biomaterials. They provide a low-cost and robust alternative to natural peroxidases, making them promising tools for creating redox-based hydrogels towards biomedical applications.
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BibTeX
@article{lopezdomene2026minimal,
title = {{A Minimal Hemin-Albumin Nanozyme with Peroxidase-like Activity Enabling Tyrosine-Crosslinked Hydrogel Formation}},
author = {Rocío López-Domene and Alice Delhaes and Arthur Lamouroux and Maria Haykal and Léna Alembik and Thomas Daubon and Océane Martin and Sébastien Lecommandoux and Elisabeth Garanger},
journal = {ACS Applied Materials \& Interfaces},
year = {2026},
month = aug,
doi = {10.1021/acsami.6c10477},
url = {https://hal.science/hal-05764606v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A Minimal Hemin-Albumin Nanozyme with Peroxidase-like Activity Enabling Tyrosine-Crosslinked Hydrogel Formation
AU - Rocío López-Domene
AU - Alice Delhaes
AU - Arthur Lamouroux
AU - Maria Haykal
AU - Léna Alembik
AU - Thomas Daubon
AU - Océane Martin
AU - Sébastien Lecommandoux
AU - Elisabeth Garanger
PY - 2026
DA - 2026/08/31
JO - ACS Applied Materials & Interfaces
DO - 10.1021/acsami.6c10477
UR - https://hal.science/hal-05764606v1
AB - Heme enzymes catalyze key oxidative reactions, yet their use in biotechnology is often limited by high production costs, low stability, and intricate operational conditions. Hemin, the catalytic iron-porphyrin cofactor of heme enzymes, has been explored as an alternative. However, its practical use is limited by its aggregation and deactivation in aqueous media. Here, we report a minimal biomimetic nanozyme based on the stabilization of hemin with bovine serum albumin (BSA) to enable aqueous catalysis and hydrogel formation under mild aqueous conditions. Through alkaline-mediated synthesis, hemin was stabilized with BSA, allowing the generation of a Hemin@BSA noncovalent hybrid with peroxidase- and catalase-like activity, outperforming free hemin or BSA complexed with hemin prepared under physiological conditions. Beyond standard peroxidase assays, Hemin@BSA catalyzed the oxidative C–C coupling of N-acetyl-tyrosine (NAT), yielding dityrosine as the main product. This enzymatic-like property was successfully applied at the macromolecular level, enabling the crosslinking of hyaluronic acid-tyramine (HA-TyrA) conjugates, yielding the formation of hydrogel networks with mechanical properties comparable to HRP-mediated crosslinked hydrogels. The cytotoxicity of hemin and Hemin@BSA was evaluated in both U87 glioblastoma and normal human astrocytes (NHA) cells, while cellular uptake and reactive oxygen species (ROS) generation were investigated in U87 cells, demonstrating efficient cellular uptake of Hemin@BSA and higher ROS levels induced by free hemin compared with Hemin@BSA. Overall, simple heme-protein complexes lie as the interface between molecular catalysts and functional biomaterials. They provide a low-cost and robust alternative to natural peroxidases, making them promising tools for creating redox-based hydrogels towards biomedical applications.
SN - 1944-8244
SN - 1944-8252
ER -