PT  - JOURNAL ARTICLE
AU  - Ji-Won Seo
AU  - Kaiyu Fu
AU  - Santiago Correa
AU  - Michael Eisenstein
AU  - Eric A. Appel
AU  - H. Tom Soh
TI  - Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals
AID  - 10.1101/2021.07.03.451023
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.03.451023
4099  - http://biorxiv.org/content/early/2021/07/04/2021.07.03.451023.short
4100  - http://biorxiv.org/content/early/2021/07/04/2021.07.03.451023.full
AB  - The efficacy and safety of a chemotherapy regimen fundamentally depends on its pharmacokinetics. This is currently measured based on blood samples, but the abnormal vasculature and physiological heterogeneity of the tumor microenvironment can produce radically different drug pharmacokinetics relative to the systemic circulation. We have developed an implantable microelectrode array sensor that can collect such tissue-based pharmacokinetic data by simultaneously measuring intratumoral pharmacokinetics from multiple sites. We employ gold nanoporous microelectrodes that maintain robust sensor performance even after repeated tissue implantation and extended exposure to the tumor microenvironment. We demonstrate continuous in vivo monitoring of concentrations of the chemotherapy drug doxorubicin at multiple tumor sites in a rodent model, and demonstrate clear differences in pharmacokinetics relative to the circulation that could meaningfully affect drug efficacy and safety. This platform could prove valuable for preclinical in vivo characterization of cancer therapeutics, and may offer a foundation for future clinical applications.Competing Interest StatementThe authors have declared no competing interest.