Micelle-based activatable probe for in vivo near-infrared optical imaging of cancer biomolecules

Near-infrared (NIR: 800-1000 nm) fluorescent probes, which activate their fluorescence following interaction with functional biomolecules, are desirable for noninvasive and sensitive tumor diagnosis due to minimal tissue interference. Focusing on bioavailability and applicability, we developed a probe with a self-assembling polymer micelle, a lactosome, encapsulating various quantities of NIR dye (IC7-1). We also conjugated anti-HER2 single chain antibodies to the lactosome surface and examined the probe’s capacity to detect HER2 in cells and in vivo. Micelles encapsulating 20 mol% IC7-1 (hIC7L) showed 30-fold higher fluorescence (λem: 858 nm) after micelle denaturation compared to aqueous buffer. Furthermore, antibody modification allowed specific activation of the probe (HER2-hIC7L) following internalization by HER2-positive cells, with the probe concentrating in lysosomes. HER2-hIC7L intravenously administered to mice clearly and specifically visualized HER2-positive tumors by in vivo optical imaging. These results indicate that HER2-hIC7L is a potential activatable NIR probe for sensitive tumor diagnosis.From the Clinical EditorNear-infrared probes that activate their fluorescence following interaction with specific biomolecules are desirable for noninvasive and sensitive tumor detection due to minimal tissue interference. This team of authors developed a probe termed hIC7L and demonstrate its potential in HER2 tumor diagnosis.

Graphical AbstractWe describe an NIR fluorescence activatable probe (HER2-hIC7L) composed of a self-assembling polymer micelle encapsulating quantities of near-infrared (NIR) fluorophore (IC7-1) with a surface modification by anti-HER2 single chain antibodies. HER2-hIC7L first interacts with HER2 on tumor cells via immunoreaction, followed by probe internalization by the cells, whereupon denaturation causes probe dequenching and a 30-fold increase in fluorescence. The probe could clearly visualize HER2-positive tumors but not HER2-negative tumors in in vitro and in vivo studies. Therefore, HER2-hIC7L would be effective for in vivo detection of HER2-expressing tumors.Figure optionsDownload high-quality image (139 K)Download as PowerPoint slide