A caspase-3 activatable photoacoustic probe for in vivo imaging of tumor apoptosis.

Abstract

Photoacoustic (PA) imaging is an emerging imaging technique, which combines high spatial resolution and deep tissue penetration of ultrasound imaging with high sensitivity of fluorescence imaging. In the past few years, PA has shown promise for noninvasive imaging of biomolecules in vivo. In this chapter, we present the synthesis and application of a tumor targeting and caspase-3 activatable PA probe (1-RGD) for real-time and noninvasive imaging of tumor apoptosis. 1-RGD can be efficiently delivered into tumor tissues and recognized by caspase-3, which triggered efficient proteolysis of DEVD substrate and subsequent intramolecular macrocyclization, followed by in situ self-assembly into nanoparticles, leading to prolonged retention in apoptotic tumors and enhanced PA signals. With 1-RGD, high-resolution 3D PA images of tumor tissues can be obtained, allowing to report on the activity and distribution of caspase-3 within DOX-treated tumors, which was helpful for early monitoring of tumor response to therapy. We provide detailed protocols for the synthesis, in vitro characterization and in vivo applications of 1-RGD.