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Issue 35, 2019
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Seconds-resolved pharmacokinetic measurements of the chemotherapeutic irinotecan in situ in the living body

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Abstract

The ability to measure drugs in the body rapidly and in real time would advance both our understanding of pharmacokinetics and our ability to optimally dose and deliver pharmacological therapies. To this end, we are developing electrochemical aptamer-based (E-AB) sensors, a seconds-resolved platform technology that, as critical for performing measurements in vivo, is reagentless, reversible, and selective enough to work when placed directly in bodily fluids. Here we describe the development of an E-AB sensor against irinotecan, a member of the camptothecin family of cancer chemotherapeutics, and its adaptation to in vivo sensing. To achieve this we first re-engineered (via truncation) a previously reported DNA aptamer against the camptothecins to support high-gain E-AB signaling. We then co-deposited the modified aptamer with an unstructured, redox-reporter-modified DNA sequence whose output was independent of target concentration, rendering the sensor's signal gain a sufficiently strong function of square-wave frequency to support kinetic-differential-measurement drift correction. The resultant, 200 μm-diameter, 3 mm-long sensor achieves 20 s-resolved, multi-hour measurements of plasma irinotecan when emplaced in the jugular veins of live rats, thus providing an unprecedentedly high-precision view into the pharmacokinetics of this class of chemotherapeutics.

Graphical abstract: Seconds-resolved pharmacokinetic measurements of the chemotherapeutic irinotecan in situ in the living body

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Publication details

The article was received on 27 Mar 2019, accepted on 05 Jul 2019 and first published on 22 Jul 2019


Article type: Edge Article
DOI: 10.1039/C9SC01495K
Chem. Sci., 2019,10, 8164-8170
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Seconds-resolved pharmacokinetic measurements of the chemotherapeutic irinotecan in situ in the living body

    A. Idili, N. Arroyo-Currás, K. L. Ploense, A. T. Csordas, M. Kuwahara, T. E. Kippin and K. W. Plaxco, Chem. Sci., 2019, 10, 8164
    DOI: 10.1039/C9SC01495K

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