A Bivalent Activatable Fluorescent Probe for Screening and Intravital Imaging of Chemotherapy-Induced Cancer Cell Death

Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202113020. doi: 10.1002/anie.202113020. Epub 2021 Dec 16.

Abstract

The detection and quantification of apoptotic cells is a key process in cancer research, particularly during the screening of anticancer therapeutics and in mechanistic studies using preclinical models. Intravital optical imaging enables high-resolution visualisation of cellular events in live organisms; however, there are few fluorescent probes that can reliably provide functional readouts in situ without interference from tissue autofluorescence. We report the design and optimisation of the fluorogenic probe Apotracker Red for real-time detection of cancer cell death. The strong fluorogenic behaviour, high selectivity, and excellent stability of Apotracker Red make it a reliable optical reporter for the characterisation of the effects of anticancer drugs in cells in vitro and for direct imaging of chemotherapy-induced apoptosis in vivo in mouse models of breast cancer.

Keywords: apoptosis; breast cancer; chemotherapy; fluorogenic probes; peptides.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Female
  • Fluorescent Dyes* / chemical synthesis
  • Fluorescent Dyes* / chemistry
  • Fluorescent Dyes* / pharmacology
  • Humans
  • Mice
  • Optical Imaging

Substances

  • Fluorescent Dyes
  • Antineoplastic Agents