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- Title
Structure-switching aptamer sensors for the specific detection of piperaquine and mefloquine.
- Authors
Coonahan, Erin S.; Yang, Kyung-Ae; Pecic, Stevan; De Vos, Maarten; Wellems, Thomas E.; Fay, Michael P.; Andersen, John F.; Tarning, Joel; Long, Carole A.
- Abstract
Diligent drug detection: Plasmodium falciparum resistance to slow-clearing artemisinin-based combination therapies is an emerging problem in the fight against malaria. Rather than relying on liquid chromatography–mass spectrometry, Coonahan et al. developed a rapid method using aptamer sensors to detect antimalarial compounds in human blood samples and crushed tablets. Aptamers specific to two antimalarial drugs, piperaquine and mefloquine, were selected and used to develop fluorescent sensors that detected the drugs in drug-spiked human serum and blood from patients with malaria, and modified versions of the sensors detected the amount of drug in a dissolved, crushed piperaquine tablet. This assay could help improve tracking of antimalarial drug use and parasite resistance. Tracking antimalarial drug use and efficacy is essential for monitoring the current spread of antimalarial drug resistance. However, available methods for determining tablet quality and patient drug use are often inaccessible, requiring well-equipped laboratories capable of performing liquid chromatography–mass spectrometry (LC-MS). Here, we report the development of aptamer-based fluorescent sensors for the rapid, specific detection of the antimalarial compounds piperaquine and mefloquine—two slow-clearing partner drugs in current first-line artemisinin-based combination therapies (ACTs). Highly selective DNA aptamers were identified that bind piperaquine and mefloquine with dissociation constants (Kd's) measured in the low nanomolar range via two independent methods. The aptamers were isolated from a library of single-stranded DNA molecules using a capture–systematic evolution of ligands by exponential enrichment (SELEX) technique and then adapted into structure-switching aptamer fluorescent sensors. Sensor performance was optimized for the detection of drug from human serum and crushed tablets, resulting in two sensing platforms. The patient sample platform was validated against an LC-MS standard drug detection method in samples from healthy volunteers and patients with malaria. This assay provides a rapid and inexpensive method for tracking antimalarial drug use and quality for the containment and study of parasite resistance, a major priority for malaria elimination campaigns. This sensor platform allows for flexibility of sample matrix and can be easily adapted to detect other small-molecule drugs.
- Subjects
APTAMERS; LIQUID chromatography-mass spectrometry; MEFLOQUINE; DRUG utilization; SINGLE-stranded DNA; DETECTORS
- Publication
Science Translational Medicine, 2021, Vol 13, Issue 585, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abe1535