Tumor-activatable ultrasmall nanozyme generator for enhanced penetration and deep catalytic therapy
| Autor: | Zhengwei Liu, Si Wu, Kai Dong, Yanjuan Sang, Xinping Liu, Ya Zhou, Tingting Cui, Jinsong Ren, Xiaogang Qu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Radical
Biophysics chemistry.chemical_element Bioengineering 02 engineering and technology Oxygen Catalysis Biomaterials Glucose Oxidase 03 medical and health sciences chemistry.chemical_compound Neoplasms Tumor Microenvironment Humans Glucose oxidase Hydrogen peroxide 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species biology Penetration (firestop) 021001 nanoscience & nanotechnology chemistry Mechanics of Materials Ceramics and Composites biology.protein Reactive Oxygen Species 0210 nano-technology Peroxidase |
| Zdroj: | Biomaterials. 258:120263 |
| ISSN: | 0142-9612 |
| Popis: | Tumor-activatable ultrasmall nanozyme generation is an unprecedented strategy to overcome intrinsically fatal defects of traditional reactive oxygen species (ROS)-based nanoagents for deep tumor penetration, including limited tissue-penetrating depth of external energy, heavy reliance on oxygen and nonspecific toxicity of therapeutic agents. Here, based on the cascade reaction between glucose oxidase (GOx) and ultrasmall peroxidase nanozyme embedded into acid-dissociable zeolitic imidazolate framework-8 (ZIF-8), such a tumor-activatable ultrasmall nanozyme generator is designed for enhanced penetration and deep catalytic therapy. With the aid of mildly acidic tumor microenvironment, the produced gluconic acid from intratumoral glucose can gradually induce the dissociation of ZIF-8 to release ultrasmall peroxidase nanozyme with significant intratumoral penetration. On the other hand, the generated hydrogen peroxide with relatively long-life can be subsequently catalyzed by penetrated peroxidase nanozyme into toxic hydroxyl radicals for deep catalytic therapy. In this way, the well-designed nanoplatform not only can greatly enhance tumor penetration but also directly induce exogenous ROS without oxygen participation and external energy input, thereby thoroughly avoiding the inactivation of traditional ROS-based nanoagents in the extremely hypoxic tumor center and finally resulting in remarkable deep catalytic therapy. |
| Databáze: | OpenAIRE |
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