Enhanced multienzyme catalytic activity of Mn MOF induced by bioligands for efficient tumor therapy

Nanozymes, as substitutes for natural enzymes, are widely used in various fields, such as cancer treatment. However, most nanozymes have low catalytic activity and selectivity, greatly limiting their clinical applications. Here, we propose a new design concept for nanozymes: modifying nanozymes with suitable multifunctional bioligands. This approach not only endows multiple biological functions but also enhances the multienzyme activity of nanozymes and avoids the effect of surface modification on nanozyme activity. In brief, this paper uses multifunctional bioligands to modify Mn MOF to obtain the nanozyme HPMZIF, which exhibits excellent biocompatibility and tumor-targeting ability. Interestingly, polyethyleneimine (PEI) modification not only effectively enhances the biocompatibility of Mn MOF, but also increases the peroxidase (POD)-, oxidase (OXD)- and glutathione peroxidase (GPx)-like activities of Mn MOF nanozymes. Furthermore, hyaluronic acid (HA) modification imparts the Mn MOF nanozymes with tumor targeting ability and enhanced the OXD- and GPx-like activities of the Mn MOF nanozymes. Ultimately, our nanoplatform cascade enhanced pyroptosis, chemotherapy, and chemodynamic therapy (CDT), significantly inhibiting the growth of 4T1 xenograft tumors. In summary, this work provides a feasible strategy for designing nanozymes with high activity and diverse biological functions, and offers new perspectives on the clinical translation of nanozymes.