1. Supramolecular amino acid-based metallo-nanozyme through multicomponent coordination self-assembly for in-site tumor synergistic catalytic-chemotherapy.
- Author
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Zhang, Shuo, Li, Yongxin, Liu, Chunlei, Zhang, Yanhui, Sun, Pan, Lan, Xiaopeng, and Liu, Chunzhao
- Subjects
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BIOMOLECULES , *TUMOR growth , *SMALL molecules , *HYDROXYL group , *CISPLATIN , *HYDROGEN peroxide , *COORDINATION polymers , *PEROXIDASE - Abstract
Peroxidase-like metallo-nanozyme is developed based on multicomponent cooperative coordination among amino acid, metal ion and therapeutic agent, the metallo-nanozyme achieves synergetic chemo-catalytic therapy through depleting high-level glutathione in tumor cell and converting Fe3+ to Fe2+ for catalyzation of hydrogen peroxide into highly cytotoxic hydroxyl radical, as well as the specific activation of chemical drugs for enhanced chemotherapy. [Display omitted] • Peroxidase-like metallo-nanozymes are simply constructed by amino acid-based cooperative coordinated self-assembly. • The biomimetic nanozymes demonstrate tumor in-site activated catalytic-chemotherapy. • The metallo-nanozymes suppress remarkably tumor growth and without any systemic toxicity. 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 (H 2 O 2) 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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