TY - JOUR
T1 - A Bivalent Activatable Fluorescent Probe for Screening and Intravital Imaging of Chemotherapy‐Induced Cancer Cell Death
AU - Barth, Nicole D.
AU - Mendive‐tapia, Lorena
AU - Subiros‐funosas, Ramon
AU - Ghashghaei, Ouldouz
AU - Lavilla, Rodolfo
AU - Maiorino, Laura
AU - He, Xue‐yan
AU - Dransfield, Ian
AU - Egeblad, Mikala
AU - Vendrell, Marc
N1 - Funding Information:
N.D.B. acknowledges funding from the Engineering and Physical Sciences Research Council (EP/L016559/1). L.M.T. acknowledges the support of Fundacion Antonio Martin Escudero (FAME) in the form of a postdoctoral fellowship. R.S.F. acknowledges an MSCA Individual Fellowship (659046). R.L. acknowledges funding from the Ministry of Science and Innovation-Spain (PID2019-107991RB-I00). X.Y.H was supported by the 2021 AACR-AstraZeneca Breast Cancer Research Fellowship (21–40-12-HE). M.E. acknowledges funding from Cold Spring Harbor Laboratory Cancer Center (P30-CA045508), Northwell Health, and the Thompson Family Foundation. M.V. acknowledges funding from an ERC Consolidator Grant (771443), the Wellcome Trust iTPA (PIII-006) and The Royal Society (RG160289). The authors thank the technical support from the QMRI Flow Cytometry and Confocal Advanced Light Microscopy facilities at the University of Edinburgh and Luxembourg BioTechnologies Ltd (Rehovot) for the kind supply of reagents for peptide synthesis.
Funding Information:
N.D.B. acknowledges funding from the Engineering and Physical Sciences Research Council (EP/L016559/1). L.M.T. acknowledges the support of Fundacion Antonio Martin Escudero (FAME) in the form of a postdoctoral fellowship. R.S.F. acknowledges an MSCA Individual Fellowship (659046). R.L. acknowledges funding from the Ministry of Science and Innovation‐Spain (PID2019‐107991RB‐I00). X.Y.H was supported by the 2021 AACR‐AstraZeneca Breast Cancer Research Fellowship (21–40‐12‐HE). M.E. acknowledges funding from Cold Spring Harbor Laboratory Cancer Center (P30‐CA045508), Northwell Health, and the Thompson Family Foundation. M.V. acknowledges funding from an ERC Consolidator Grant (771443), the Wellcome Trust iTPA (PIII‐006) and The Royal Society (RG160289). The authors thank the technical support from the QMRI Flow Cytometry and Confocal Advanced Light Microscopy facilities at the University of Edinburgh and Luxembourg BioTechnologies Ltd (Rehovot) for the kind supply of reagents for peptide synthesis.
Publisher Copyright:
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
PY - 2022/1/26
Y1 - 2022/1/26
N2 - 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. Here 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.
AB - 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. Here 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.
U2 - 10.1002/anie.202113020
DO - 10.1002/anie.202113020
M3 - Article
VL - 61
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
SN - 1433-7851
IS - 5
ER -