An Indocyanine Green‐Based Nanoprobe for In Vivo Detection of Cellular Senescence

There is an urgent need to improve conventional cancer‐treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo‐ or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self‐assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy. Sound of Senescence: A nanostructured organic probe, NanoJaggs, can be used as photoacoustic contrast agent for in vivo imaging of the senescent cell burden in post‐chemotherapy tumors. Made of indocyanine green (ICG) dimers, 30 nm nanoparticles exploit an active endocytosis mechanism and increase the number of lysosomes to specifically light up senescent cells implicated in cancer initiation and progression.