Supramolecular amino acid-based metallo-nanozyme through multicomponent coordination self-assembly for in-site tumor synergistic catalytic-chemotherapy

Simple biomolecules-based supramolecular self-assembly hold great promise on the fabrication of nanozyme for mimicking natural enzyme, both structurally and functionally. However, it remains a formidable challenge to design of tumor-specific nanozyme with promoted therapeutic efficiencies starting from such small biological molecule combinations and their cooperative interactions. Inspired by the metalloenzyme in living systems, i.e., peroxidase, herein the construction of metallo-nanozyme through a facile multicomponent coordination self-assembly based on the combination of amino acid, chemotherapeutic motif and metal ions is reported. The resulting metallo-nanozyme possess uniform size distribution, well-defined spherical nanostructure and high chemical drugs contents. Most importantly, the metallo-nanozyme depletes specifically high-level glutathione (GSH) in tumor cell and converts Fe³⁺ to Fe²⁺ for subsequent transformation of overproduced hydrogen peroxide (H₂O₂) into highly cytotoxic hydroxyl radical (·OH) in peroxidase-like catalytic manner. Meanwhile, the metallo-nanozyme are also activated in situ to release the chemical drugs in tumor cell for enhanced chemotherapy. In vitro and in vivo evaluations demonstrate that the supramolecular metallo-nanozyme suppresses remarkably tumor growth via combined catalytic-chemotherapy and without any systemic toxicity. Therefore, this study demonstrates that the tumor-specific biomimetic nanozyme with advanced catalytic therapeutic efficacy could be achieved through cooperative coordination of small biomolecules or therapeutic drugs, opening up opportunities in the development of catalytic anticancer nanozyme for efficiently combat cancers.