Ratiometric Fluorescence Monitoring of Antibody-Guided Drug Delivery to Cancer Cells

Dvir Poplinger, Maksym Bokan, Arkadi Hesin, Ebaston Thankarajan, Helena Tuchinsky, Gary Gellerman, Leonid Patsenker

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Ratiometric measurements utilizing two independent fluorescence signals from a dual-dye molecular system help to improve the detection sensitivity and quantification of many analytical, bioanalytical, and pharmaceutical assays, including drug delivery monitoring. Nevertheless, these dual-dye conjugates have never been utilized for ratiometric monitoring of antibody (Ab)-guided targeted drug delivery (TDD). Here, we report for the first time on the new, dual-dye TDD system, Cy5s-Ab-Flu-Aza, comprising the switchable fluorescein-based dye (Flu) linked to the anticancer drug azatoxin (Aza), reference pentamethine cyanine dye (Cy5s), and Her2-specific humanized monoclonal Trastuzumab (Herceptin) antibody. The ability of ratiometric fluorescence monitoring of drug release was demonstrated with this model system in vitro in the example of the human breast cancer SKBR3 cell line overexpressing Her2 receptors. The proposed approach for designing ratiometric, antibody-guided TDD systems, where a "drug-switchable dye"conjugate and a reference dye are independently linked to an antibody, can be expanded to other drugs, dyes, and antibodies. Replacement of the green-emitting dye Flu, which was found not detectable in vivo, with a longer-wavelength (red or near-IR) switchable fluorophore should enable quantification of drug release in the body.

Original languageEnglish
Pages (from-to)1641-1651
Number of pages11
JournalBioconjugate Chemistry
Issue number8
StatePublished - 18 Aug 2021


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