State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
University of Science and Technology of China, Hefei, Anhui, 230029, P. R. China.
Nat Commun. 2022 Mar 18;13(1):1459. 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/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.
作为典型的生物正交反应之一，铜（I）催化的叠氮-炔环加成（CuAAC）反应在有机合成、生物缀合和表面功能化方面具有巨大的潜力。然而，Cu（I）的毒性、催化活性的低效以及现有催化剂缺乏细胞特异性靶向性，阻碍了它们在活体内系统中的实际应用。在此，我们设计并构建了一个基于 DNA 的平台，作为一种具有生物相容性、高效和精确靶向的生物正交纳米催化剂。该纳米催化剂在体外表现出优异的催化效率，比常用的催化剂 CuSO4/抗坏血酸钠高一个数量级。理论计算进一步支持了 DNA 结构及其与底物相互作用对优越催化活性的贡献。更重要的是，该系统可以通过细胞类型特异性识别在癌细胞中实现有效的前药激活，并产生比非靶向纳米催化剂高 40 倍的转化增强，从而提高抗肿瘤疗效并降低不良反应。体内肿瘤治疗证明了该系统在哺乳动物中的安全性和有效性。
