DNA-based platform for efficient and precisely targeted bioorthogonal catalysis in living systems

• Published in: Nature communications Vol. 13; no. 1; p. 1459
• Main Authors: You, Yawen, Deng, Qingqing, Wang, Yibo, Sang, Yanjuan, Li, Guangming, Pu, Fang, Ren, Jinsong, Qu, Xiaogang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 631/61; 631/61/54; 639/638/77; Alkynes; Alkynes - chemistry; Animals; Anticancer properties; Antitumor activity; Aptamers; Ascorbic acid; Azides - chemistry; Biocompatibility; Cancer; Catalysis; Catalysts; Catalytic activity; Cell activation; Chemical reactions; Chemistry; Click Chemistry - methods; Copper; Copper - chemistry; Cycloaddition; Cycloaddition Reaction; Deoxyribonucleic acid; DNA; DNA structure; Humanities and Social Sciences; Laboratories; Mammals; multidisciplinary; Nanocomposites; Nanoparticles; Science; Science (multidisciplinary); Substrates; Toxicity; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29167-x

As one of the typical bioorthogonal reactions, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction holds great potential in organic synthesis, bioconjugation, and surface functionalization. However, the toxicity of Cu(I), inefficient catalytic activity, and the lack of cell specific targeting of the existing catalysts hampered their practical applications in living systems. Herein, we design and construct a DNA-based platform as a biocompatible, highly efficient, and precisely targeted bioorthogonal nanocatalyst. The nanocatalyst presents excellent catalytic efficiency in vitro, which is one order of magnitude higher than the commonly used catalyst CuSO 4 /sodium ascorbate. The theoretical calculation further supports the contribution of DNA structure and its interaction with substrates to the superior catalytic activity. More importantly, the system can achieve efficient prodrug activation in cancer cells through cell type-specific recognition and produce a 40-fold enhancement of transformation compared to the non-targeting nanocatalyst, resulting in enhanced antitumor efficacy and reduced adverse effects. In vivo tumor therapy demonstrates the safety and efficacy of the system in mammals. Copper-click reaction has been used for a wide range of bio-conjugations but does suffer from toxicity issues. Here, the authors report on the growth of copper nanoparticles on DNA with linked aptamer targeting and demonstrate high catalytic effect and improved application due to targeting and biocompatibility.