A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy,Chemical Science

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A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy
Chemical Science ( IF 7.6 ) Pub Date : 2022-06-10 , DOI: 10.1039/d2sc02050e
Yawen You _{1,

2} , Hao Liu _{1,

2} , Jiawei Zhu _{1,

2} , Yibo Wang ₃ , Fang Pu _{1,

2} , Jinsong Ren _{1,

2} , Xiaogang Qu _{1,

2}

Affiliation

As one of the representative bioorthogonal reactions, the copper-catalyzed click reaction provides a promising approach for in situ prodrug activation in cancer treatment. To solve the issue of inherent toxicity of Cu(I), biocompatible heterogeneous copper nanoparticles (CuNPs) were developed for the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. However, the unsatisfactory catalytic activity and off-target effect still hindered their application in biological systems. Herein, we constructed a DNAzyme-augmented and targeted bioorthogonal catalyst for synergistic cancer therapy. The system could present specificity to cancer cells and promote the generation of Cu(I) via DNAzyme-induced value state conversion of DNA-templated ultrasmall CuNPs upon exposure to endogenous H₂O₂, thereby leading to high catalytic activity for in situ drug synthesis. Meanwhile, DNAzyme could produce radical species to damage cancer cells. The synergy of in situ drug synthesis and chemodynamic therapy exhibited excellent anti-cancer effects and minimal side effects. The study offers a simple and novel avenue to develop highly efficient and safe bioorthogonal catalysts for biological applications.

中文翻译：

用于协同癌症治疗的 DNAzyme 增强生物正交催化系统

作为代表性的生物正交反应之一，铜催化的点击反应为癌症治疗中的原位前药激活提供了一种有前途的方法。为了解决Cu（）的固有毒性问题，开发了生物相容性异质铜纳米粒子（CuNP）用于铜催化叠氮化物-炔环加成（CuAAC）反应。然而，催化活性不理想和脱靶效应仍然阻碍了它们在生物系统中的应用。在此，我们构建了一种 DNAzyme 增强的靶向生物正交催化剂，用于协同癌症治疗。该系统可以对癌细胞呈现特异性，并通过DNAzyme 诱导 DNA 模板超小 CuNPs 暴露于内源 H ₂ O ₂时促进 Cu() 的生成，从而对原位药物合成产生高催化活性。同时，DNAzyme可以产生自由基物质来破坏癌细胞。原位药物合成和化学动力学疗法的协同作用表现出优异的抗癌效果和最小的副作用。该研究为开发用于生物应用的高效且安全的生物正交催化剂提供了一种简单而新颖的途径。

更新日期：2022-06-10

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