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A DNA-Gated and Self-Protected Bioorthogonal Catalyst for Nanozyme-Assisted Safe Cancer Therapy |
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| Authors: | Yanjie Zhang Lu Zhang Wenjie Wang Qingqing Deng Mengmeng Liu Zitong Zhu Hao Liu Prof. Jinsong Ren Prof. Xiaogang Qu |
| Affiliation: | 1. State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022 Changchun, China School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026 Hefei, China Contribution: Data curation (lead);2. State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022 Changchun, China;3. State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022 Changchun, China School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026 Hefei, China Contribution: Data curation (supporting);4. State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022 Changchun, China School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026 Hefei, China Contribution: Methodology (supporting) |
| Abstract: | Transition metal catalysts (TMCs) mediated bioorthogonal uncaging catalysis has sparked increasing interest in prodrug activation. However, due to their “always-on” catalytic activity as well as the complex and catalytic-detrimental intracellular environment, the biosafety and therapeutic efficiency of TMCs are unsatisfactory. Herein, a DNA-gated and self-protected bioorthogonal catalyst has been designed by modifying nanozyme-Pd0 with highly programmable nucleic acid (DNA) molecules to achieve efficient intracellular drug synthesis for cancer therapy. Monolayer DNA molecules could endow the catalyst with targeting and perform as a gatekeeper to achieve selective prodrug activation within cancer cells. Meanwhile, the prepared graphitic nitrogen-doped carbon nanozyme with glutathione peroxidase (GPx) and catalase (CAT)-like activities could improve the catalytic-detrimental intracellular environment to prevent the catalyst from being inactivated and sensitize the subsequent chemotherapy. Overall, we believe that our work will promote the development of secure and efficient bioorthogonal catalytic systems and provide new insights into novel antineoplastic platforms. |
| Keywords: | Bioorthogonal Catalysis Cancer Therapy Intracellular Drug Synthesis Nanozyme Oxidative Stress |