Abstract

Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL780/FL1113), but a small PA ratio between 755 and 905 nm (PA755/PA905). Oxidation of 1-Br-Et by •OH decreases the FL780/FL1113 while concurrently increasing the PA755/PA905, allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy.

Highlights

  • Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (OH) production

  • Radiation therapy (RT) is a clinically widely used cancer treatment strategy referring to radiation of tumor tissues by ionizing beams (e.g., X-ray)[8,9,10,11]; there is mounting evident that the OH production via radiolysis of water molecules plays an important role in killing cancer cells, as more than 50% of DNA damage in a standard radiotherapy is caused by OH3,12

  • The normalized PA755/ PA905 ratio (2.23 ± 0.12) in Fenton reagent-treated cells was ~1.7fold higher than that in tempol-treated cells (1.32 ± 0.19) (Fig. 4d, e). These findings demonstrate that 1-NP was able to detect Fenton reagent-induced OH production in RAW264.7 cells. 1-NP was further applied for the detection of endogenous OH fluctuation in RAW264.7 cells upon stimulation with lipopolysaccharide (LPS)[63] or phorbol 12-myristate 13-acetate (PMA)[64], which showed obviously decreased FL at 780 nm but strong NIR-II FL at 1113 nm in relative to unstimulated control cells (Fig. 4a, c)

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Summary

Introduction

Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (OH) production. While a few FL probes capable of emitting their FL in nearinfrared (NIR) regions have been reported, none of them has been applied for in vivo imaging of tumor OH28,33–36. They were all designed based on the change of FL intensity at a single wavelength, which could be largely influenced by the fluctuation of probe’s concentration in the dynamic and complex in vivo environments, potentially leading to false-positive results. People have recently reported several ratiometric FL imaging probes based on a FL intensity ratio at two different wavelengths, which might improve accuracy for the detection of intracellular OH as the built-in self-calibration effect could allow to minimize falsepositive errors resulting from environmental factors[28,37,38,39]

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