The study introduces a novel biocompatible, injectable organic nanoprobe called NanoJagg, which is designed to detect cellular senescence in vivo. NanoJagg is derived from the self-assembly of indocyanine green (ICG) dimers and is characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. The probe selectively accumulates in senescent cells, particularly in their lysosomes, due to the enlarged lysosomal compartment in senescent cells. In vitro, ex vivo, and in vivo studies demonstrate that NanoJagg effectively detects senescent cells, with enhanced accumulation in senescent cells compared to non-senescent cells. The probe's accumulation is regulated by clathrin-mediated endocytosis and macropinocytosis, and its signal correlates with the increased lysosomal content in senescent cells. NanoJagg shows promise as a contrast agent for PAT imaging, providing a practical tool for monitoring senescent cell burden in solid tumors after chemotherapy or radiotherapy. The study highlights the potential of NanoJagg for clinical translation and its role in improving cancer treatment by preventing detrimental side effects, cancer recurrence, and metastases.The study introduces a novel biocompatible, injectable organic nanoprobe called NanoJagg, which is designed to detect cellular senescence in vivo. NanoJagg is derived from the self-assembly of indocyanine green (ICG) dimers and is characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. The probe selectively accumulates in senescent cells, particularly in their lysosomes, due to the enlarged lysosomal compartment in senescent cells. In vitro, ex vivo, and in vivo studies demonstrate that NanoJagg effectively detects senescent cells, with enhanced accumulation in senescent cells compared to non-senescent cells. The probe's accumulation is regulated by clathrin-mediated endocytosis and macropinocytosis, and its signal correlates with the increased lysosomal content in senescent cells. NanoJagg shows promise as a contrast agent for PAT imaging, providing a practical tool for monitoring senescent cell burden in solid tumors after chemotherapy or radiotherapy. The study highlights the potential of NanoJagg for clinical translation and its role in improving cancer treatment by preventing detrimental side effects, cancer recurrence, and metastases.