Weber, Judith, Bollepalli, Laura, Belenguer, Ana M, Antonio, Marco Di, De Mitri, Nicola, Joseph, James, Balasubramanian, Shankar, Hunter, Christopher A and Bohndiek, Sarah E (2019) An Activatable Cancer-Targeted Hydrogen Peroxide Probe for Photoacoustic and Fluorescence Imaging. Cancer research, 79 (20). pp. 5407-5417. ISSN 1538-7445

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 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 (HO). 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 HO. The optical properties of the probe were characterized using absorption, fluorescence, and photoacoustic measurements; upon addition of pathophysiologic HO concentrations, a clear increase in fluorescence and red-shift of the absorption and photoacoustic spectra were observed. Studies performed 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 HO. In conclusion, the reported probe shows promise for the 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. http://cancerres.aacrjournals.org/content/canres/79/20/5407/F1.large.jpg.

Item Type:	Article
Date Deposited:	27 Jan 2022 00:45
Last Modified:	27 Jan 2022 00:45
URI:	https://oak.novartis.com/id/eprint/46679