In Vivo Monitoring of Cellular Senescence by Photoacoustic and Fluorescence Imaging Utilizing a Nanostructured Organic Probe

Abstract

ABSTRACTSenescent cells accumulate in multiple age-related disorders, including cancer, exacerbating the pathological manifestations, and the eradication of these cells has emerged as a promising therapeutic strategy. Despite the impact of senescence in diseases, the development of tools to monitor the senescent burdenin vivoremains a challenge due to their suboptimal specificity, translatability, and tissue penetrance. Here, we have designed a nanostructured organic probe (NanoJaggs) based on biocompatible indocyanine green dye (ICG) building blocks forming J-aggregates, which possess distinct spectral properties allowing both fluorescence and photoacoustic tomography (PAT) detection. We show that NanoJaggs are taken up by an active process of endocytosis and exhibit selective accumulation at the lysosomal compartment in severalin vitromodels for senescence. Finally, NanoJagg probe is validated in twoin vivostudies including live PAT imaging and shows remarkable specificity to tumours with chemotherapy-induced senescence compared to untreated proliferative tumors.In vitro, ex vivoandin vivoall indicate that NanoJaggs are a clinically translatable tool for detection of senescence and their robust PAT signal makes them suitable for longitudinal monitoring of the senescent burden in solid tumors after chemo or radiotherapy.