Citation: ZHANG Ben-Hua, LIANG Ting-Xi-Zi, HE Zhi-Mei, JIANG Yao-Wen, HUANG Shan, MIN Qian-Hao. Zinc Peroxide-Mesoporous Silica Core-Shell Dual-Enzyme Nanoreactors for Gene-Chemodynamic Synergistic Therapy of Cancer[J]. Chinese Journal of Analytical Chemistry, ;2021, 49(11): 1855-1863. doi: 10.19756/j.issn.0253-3820.210506 shu

Zinc Peroxide-Mesoporous Silica Core-Shell Dual-Enzyme Nanoreactors for Gene-Chemodynamic Synergistic Therapy of Cancer

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

Corresponding author: MIN Qian-Hao, minqianhao@nju.edu.cn
Received Date: 12 May 2021
Revised Date: 11 August 2021

Fund Project: Supported by the National Natural Science Foundation of China (Nos.21974062, 92053102).

Stimuli-responsiveness of nanoreactors offers a good opportunity for designing site-specific therapeutic agents to maximize the therapeutic efficacy and minimize the side effect. In this work, a dual-enzyme reactor with zinc peroxide-mesoporous silica core-shell structure was constructed for pH-responsive gene therapy and chemodynamic therapy of cancer. The ZnO₂@FcDMSN@DNAzyme/GOx (ZFDG) nanoreactors were fabricated by modifying ferrocene (Fc) on the surface of mesoporous silica-coated zinc peroxide nanoparticles, followed by electrostatic adsorption of DNAzyme and glucose oxidase (GOx) in the outer pore structures. After internalization into tumor cells, intracellular acidic environment spurred the release of Zn²⁺to activate DNAzyme, leading to the cleavage of the target mRNA for downregulation of early growth factor-1 (EGR-1) and consequent inhibition of tumor cell growth. In addition, GOx could transform abundant intracellular glucose into gluconic acid and hydrogen peroxide (H₂O₂), which increased the acidity in cells and provided massive substrates for Fenton reaction. The results showed that the presented ZFDG nanoreactors could be degraded under acidic environment and produced Zn²⁺, which further triggered gene therapy to reduce cell viability down to 70%. Upon combination with enhanced chemodynamic therapy, the cell survival rate could be further lowered to 20% when the concentration of nanoreactor was 50 μg/mL. Therefore, the collaboration of precisely triggered gene therapy and enhanced chemodynamic therapy synchronously improved the treatment efficiency and provided a potential tool for effective cancer therapy.
- Acidic environment-responsiveness,
- Gene therapy,
- Enhanced chemodynamic therapy,
- Synergistic therapy
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