A Photoacoustic Probe for the Imaging of Tumor Apoptosis by Caspase-Mediated Macrocyclization and Self-Assembly

Angew Chem Int Ed Engl. 2019 Apr 1;58(15):4886-4890. doi: 10.1002/anie.201813748. Epub 2019 Feb 20.

Abstract

Photoacoustic (PA) imaging shows promise in the sensitive detection of caspase-3 activated in early tumor apoptosis in response to chemotherapy; smart PA probes are thus in high demand. Herein, we report the first smart PA probe (1-RGD) responsive to caspase-3, enabling real-time and high-resolution imaging of tumor apoptosis. 1-RGD is designed to leverage the synergetic effect of active delivery and caspase-3 activation. It is selectively recognized by active caspase-3 to trigger peptide substrate cleavage and biocompatible macrocyclization-mediated self-assembly, leading to an amplified PA imaging signal and prolonged retention in apoptotic tumor cells. Strong, high-resolution PA images are obtained in chemotherapy-induced apoptotic tumors in living mice after intravenous administration with 1-RGD, facilitating sensitive reporting of caspase-3 activity and distribution within tumor tissues.

Keywords: activatable probes; apoptosis; caspase-3; photoacoustic imaging; self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Caspases / chemistry
  • Caspases / metabolism*
  • Cyclization
  • Glioblastoma / diagnostic imaging*
  • Humans
  • Macrocyclic Compounds / chemistry*
  • Macrocyclic Compounds / metabolism
  • Molecular Imaging
  • Molecular Probes / biosynthesis
  • Molecular Probes / chemistry*
  • Molecular Structure
  • Optical Imaging*
  • Photoacoustic Techniques*

Substances

  • Macrocyclic Compounds
  • Molecular Probes
  • Caspases