Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27607, United States.
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States.
J Am Chem Soc. 2024 Feb 7;146(5):3230-3240. doi: 10.1021/jacs.3c11350. Epub 2024 Jan 26.
The ability to quantify cocaine in biological fluids is crucial for both the diagnosis of intoxication and overdose in the clinic as well as investigation of the drug's pharmacological and toxicological effects in the laboratory. To this end, we have performed high-stringency selection to generate DNA aptamers that bind cocaine with nanomolar affinity and clinically relevant specificity, thus representing a dramatic improvement over the current-generation, micromolar-affinity, low-specificity cocaine aptamers. Using these novel aptamers, we then developed two sensors for cocaine detection. The first, an fluorescent sensor, successfully detects cocaine at clinically relevant levels in 50% human serum without responding significantly to other drugs of abuse, endogenous substances, or a diverse range of therapeutic agents. The second, an electrochemical aptamer-based sensor, supports the real-time, seconds-resolved measurement of cocaine concentrations in the circulation of live animals. We believe the aptamers and sensors developed here could prove valuable for both point-of-care and on-site clinical cocaine detection as well as fundamental studies of cocaine neuropharmacology.
定量检测生物体液中的可卡因对于临床诊断中毒和过量以及实验室研究药物的药理学和毒理学效应至关重要。为此,我们进行了严格的筛选,以产生与可卡因具有纳摩尔亲和力和临床相关特异性的 DNA 适体,从而与当前一代具有微摩尔亲和力和低特异性的可卡因适体相比有了显著的改进。然后,我们使用这些新型适体开发了两种可卡因检测传感器。第一个是荧光传感器,可成功检测到 50%人血清中具有临床相关性的可卡因,而对其他滥用药物、内源性物质或各种治疗药物没有明显反应。第二个是基于电化学适体的传感器,支持实时、秒分辨率测量活体动物循环中的可卡因浓度。我们相信这里开发的适体和传感器可用于即时和现场临床可卡因检测以及可卡因神经药理学的基础研究。