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

Yawen You, Qingqing Deng, Yibo Wang, Yanjuan Sang, Guangming Li (), Fang Pu (), Jinsong Ren () and Xiaogang Qu ()
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Yawen You: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
Qingqing Deng: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
Yibo Wang: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
Yanjuan Sang: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
Guangming Li: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
Fang Pu: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
Jinsong Ren: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
Xiaogang Qu: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract 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 CuSO4/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.

Date: 2022
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DOI: 10.1038/s41467-022-29167-x

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