Repository logo
 

An Activatable Cancer-Targeted Hydrogen Peroxide Probe for Photoacoustic and Fluorescence Imaging.

Accepted version
Peer-reviewed

Loading...
Thumbnail Image

Type

Article

Change log

Authors

Weber, Judith 

Abstract

Reactive oxygen species play an important role in cancer, however, their promiscuous reactivity, low abundance, and short-lived nature limit our ability to study them in real time in living subjects with conventional noninvasive imaging methods. Photoacoustic imaging is an emerging modality for in vivo visualization of molecular processes with deep tissue penetration and high spatiotemporal resolution. Here, we describe the design and synthesis of a targeted, activatable probe for photoacoustic imaging, which is responsive to one of the major and abundant reactive oxygen species, hydrogen peroxide (H2O2). This bifunctional probe, which is also detectable with fluorescence imaging, is composed of a heptamethine carbocyanine dye scaffold for signal generation, a 2-deoxyglucose cancer localization moiety, and a boronic ester functionality that specifically detects and reacts to H2O2. The optical properties of the probe were characterized using absorption, fluorescence, and photoacoustic measurements; upon addition of pathophysiologic H2O2 concentrations, a clear increase in fluorescence and red-shift of the absorption and photoacoustic spectra were observed. Studies performed in vitro showed no significant toxicity and specific uptake of the probe into the cytosol in breast cancer cell lines. Importantly, intravenous injection of the probe led to targeted uptake and accumulation in solid tumors, which enabled noninvasive photoacoustic and fluorescence imaging of H2O2. In conclusion, the reported probe shows promise for the in vivo visualization of hydrogen peroxide. SIGNIFICANCE: This study presents the first activatable and cancer-targeted hydrogen peroxide probe for photoacoustic molecular imaging, paving the way for visualization of hydrogen peroxide at high spatiotemporal resolution in living subjects.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/20/5407/F1.large.jpg.

Description

Keywords

Absorption, Radiation, Adenocarcinoma, Animals, Cell Line, Tumor, Deoxyglucose, Fluorescent Dyes, Heterografts, Humans, Hydrogen Peroxide, Liver Neoplasms, MCF-7 Cells, Mice, Mice, Nude, Molecular Imaging, Neoplasm Transplantation, Optical Imaging, Oxidative Stress, Photoacoustic Techniques, Piperazines, Tissue Distribution

Journal Title

Cancer Res

Conference Name

Journal ISSN

0008-5472
1538-7445

Volume Title

79

Publisher

American Association for Cancer Research (AACR)

Rights

All rights reserved
Sponsorship
European Commission (630729)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research UK (C14303/A17197)
Cancer Research UK (C14303/A17197)
Cancer Research UK (18618)
Cancer Research UK (CB4330)