Emission Wavelength-Tunable Bicyclic Dioxetane Chemiluminescent Probes for Precise In Vitro and In Vivo Imaging

Abstract

Chemiluminescent probes have become increasingly popular in various research areas including precise tumor imaging and immunofluorescence analysis. Nevertheless, previously developed chemiluminescence probes are mainly limited to studying oxidation reaction-associated biological events. This study presents the first example of bioimaging applicable bicyclic dioxetane chemiluminescent probes with tunable emission wavelengths that range from 525 to 800 nm. These newly developed probes were able to detect the analytes of β-Gal, H 2 O 2 , and superoxide with high specificity and a limit of detection of 77 mU L −1 , 96, and 28 nM, respectively. The bioimaging application of the probes was verified in ovarian and liver cancer cells and macrophage cells, allowing the detection of the content of β-Gal, H 2 O 2 , and superoxide inside the cells. The high specificity allowed us to image the xenografted tumor in mice. We expect that our probes will receive extensive applications in recording complex biomolecular events using noninvasive imaging techniques.

High Contrast Bioimaging of Tumor and Inflammation with a Bicyclic Dioxetane Chemiluminescent Probe

“…The chemiluminescence (CL) method is increasingly recognized as a superior tool in biomedical research and diagnostics − due to its remarkable sensitivity, favorable signal-to-noise ratio, and independence from external light excitation, which altogether enhance the precision and clarity of biomedical imaging. − Despite its proven efficacy, the deployment of CL for the concurrent visualization of tumors and inflammatory sites through ONOO – detection using a single, bespoke probe has remained uncharted territory. This is largely attributable to the scarcity of ONOO – specific CL probes, their tendency to emit at shorter wavelengths, and their limited selectivity and depth of tissue penetration. − To overcome these challenges, our study introduces a novel NIR (near-infrared) CL probe tailored to detect peroxynitrite (ONOO – ) with unparalleled sensitivity and precision, paving the way for the targeted imaging of both inflammation and tumor tissues (Figure b).…”