Research ArticleBioengineering

Real-Time, Aptamer-Based Tracking of Circulating Therapeutic Agents in Living Animals

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Science Translational Medicine  27 Nov 2013:
Vol. 5, Issue 213, pp. 213ra165
DOI: 10.1126/scitranslmed.3007095

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Tracking Drugs in Real Time

You have the drug, it’s time to give to the patient. Now, what is the ideal dose? Many drugs have unwanted side effects when given at large doses; conversely, they are not efficacious at too low of a dose. Continuously monitoring a drug as it circulates throughout the body would give doctors a better grip on personalized medicine, by allowing them to then tailor the therapeutic dose and schedule for each patient. To this end, Ferguson et al. developed a biosensor that reports the concentration of a drug in real time in live animals and in patient samples.

The microfluidic sensing device, which the authors named MEDIC (microfluidic electrochemical detector for in vivo continuous monitoring), consisted of an electrochemically modified aptamer—a oligonucleotide that is highly specific for a target drug—attached to a gold electrode, as well as a filter to prevent blood cells from clogging up the device. The electrodes reported the change in charge as the drug bound to the aptamer. Ferguson et al. used two different aptamers: one specific for doxorubicin (DOX; a cancer drug) and one for kanamycin (an antibiotic). The authors first demonstrated that MEDIC could detect submicromolar concentrations of DOX in human whole blood. The MEDIC was then hooked up to live rats to continuously draw blood for monitoring. Injecting the animals with a drug-free solution yielded no change in device signal. However, injecting therapeutically relevant doses of DOX or kanamycin—depending on the device configuration—quickly produced a signal that corresponded to the in vivo drug concentration.

Such continuous monitoring of drugs could afford clinicians the opportunity to tailor therapeutic regimens to individual patients, thus preventing toxic side effects or dialing up the drug effect. Translating this technology to people may require tweaking the sensor for longer operation times (days to weeks, versus the hours described here), as well as safety testing. Once deemed useful and safe, the device could replace periodic and disruptive blood draws at the patient’s bedside, much like continuous glucose monitors in widespread use today for diabetes.