Dual-Stimulus Responsive Near-Infrared Reversible Ratiometric Fluorescent and Photoacoustic Probe for <i>In Vivo</i> Tumor Imaging

Abstract

Tumor-specific imaging is a major challenge in clinical tumor resection. To overcome this problem, several activatable probes have been developed for use in tumor imaging. However, most of these probes are activated based on a single-factor stimulation and are irreversible. Therefore, false signals that make tumor-specific imaging difficult are easily generated. We have developed a new dual-stimulus responsive near-infrared (NIR) reversible adenosine 5'-triphosphate (ATP)-pH probe for fluorescence and photoacoustic ratiometric imaging of tumors. Since the H⁺ and ATP content is significantly higher in the tumor microenvironment than that in normal tissues, the Förster resonance energy transfer-based probe ATP-pH was constructed with silicon rhodamine as the donor, CS dye as the acceptor, and ATP/H⁺ recognition units that could only be activated when both H⁺ and ATP were connected to the acceptor. The ATP-pH probe is reversibly activated by both the H⁺ and ATP, which effectively reduces the cumulative response of the probe in circulation after intravenous injection. Further, the NIR ratiometric property of the probe makes it suitable for <i>in vivo</i> imaging. Finally, our probe was successfully utilized in ratiometric photoacoustic and fluorescence tumor imaging and ratiometric fluorescence imaging-guided tumor resection.