Activatable Oligomerizable Imaging Agents for Photoacoustic Imaging of Furin-Like Activity in Living Subjects

Abstract

Photoacoustic imaging (PA) is continuing to be applied for physiological imaging and more recently for molecular imaging of living subjects. Owing to its high spatial resolution in deep tissues, PA imaging holds great potential for biomedical applications and molecular diagnostics. There is however a lack of probes for targeted PA imaging, especially in the area of enzyme-activatable probes. Here we introduce a molecular probe, which upon proteolytic processing is retained at the site of enzyme activity and provides PA contrast. The probe oligomerizes via a condensation reaction and accumulates in cells and tumors that express the protease. We demonstrate that this probe reports furin and furin-like activity in cells and tumor models by generating a significantly higher photoacoustic signal relative to furin-deficient and non-target controls. This probe could report enzyme activity in living subjects at depths significantly greater than fluorescence imaging probes and has potential for molecular imaging in deep tumors.

H 2 O 2 -responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay

“…For example, many types of nanoparticles with strong and constant NIR absorbance are often used for enhanced blood pool imaging and PA imaging of tumors (15,16,19). In addition, smart PA imaging nanoprobes with their absorbance spectra responsive to certain physiological signals such as reactive oxygen species (ROS), pH, and enzymes have also received substantial interest in recent years (12,21,22), because such a type of imaging would provide critical information directly related to disease progression and mechanisms. However, a sensitive and biocompatible nanoprobe that can precisely detect H 2 O 2 in vivo by PA imaging has not yet been reported, to our best knowledge.…”

Listen to the chemical and histological information in biological tissue

“…An example of PAI enhanced by oligomerizable agents is shown in Fig. 3 [42], where the contrast of PAI of mice tumors is increased significantly after the agent administration.…”

“…The applications of exogenous contrast agents give PAI the ability to measure chemical and biological information at the molecular level. A great variety of PA contrast agents have been developed in recent years, such as organic dyes [38], metallic nanoparticles [39,40], carbon nanotubes [41], and oligomer [42]. These agents have been wildly used in bio-medical and bio-chemical research.…”

“…These agents have been wildly used in bio-medical and bio-chemical research. Based on the passive targeting mechanism, agents can significantly increase the contrast of PAI in cancer detecting [38,42] and other applications [43]. PAI based on Doppler effect can achieve accurate flow measurements when powered by nanoparticles [44].…”

Quantitative Analysis of Caspase-1 Activity in Living Cells Through Dynamic Equilibrium of Chlorophyll-Based Nano-assembly Modulated Photoacoustic Signals

“…[1][2][3][4] In these cases, the small molecules have been designed with enzymatic-response and self-assembled inside cells or living bodies for determining enzyme activity. The pilot studies based on this strategy proved to be effective in biology and medicine [4][5][6] .…”