2024 | Andrew G. Baker, Muhamad Hartono, Hui-Ling Ou, Andrea Bistrović Popov, Emma L. Brown, James Joseph, Monika Golinska, Estela González-Gualda, David Macias, Jianfeng Ge, Mary Denholm, Samir Morsli, Chandan Sanghera, Thomas R. Else, Heather F. Greer, Aude Vernet, Sarah E. Bohndiek, Daniel Muñoz-Espin, Ljiljana Fruk
A novel indocyanine green (ICG)-based nanoprobe, NanoJagg, was developed for in vivo detection of cellular senescence. NanoJagg is a biocompatible, injectable organic nanoprobe that selectively accumulates in senescent cells and is characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. The nanoprobe was synthesized through the self-assembly of ICG dimers under mild and scalable conditions, resulting in nanosized J-aggregate structures with high purity, physicochemical stability, and biocompatibility. NanoJagg was shown to be selectively taken up by senescent cells, accumulating in lysosomes, and exhibited a significant increase in fluorescence and PAT signals in senescent cells compared to non-senescent cells. The uptake of NanoJagg was found to be dependent on clathrin-mediated endocytosis and macropinocytosis. In vivo studies using tumor xenografts confirmed that NanoJagg could effectively detect chemotherapy-induced senescence, with a significant increase in signal in senescent tumors compared to control tumors. Additionally, NanoJagg was shown to be suitable for PAT imaging, providing high-resolution images of senescent cells with a strong PAT signal. The results demonstrate that NanoJagg is a promising tool for the detection and monitoring of senescence in various disease models, including cancer. The nanoprobe is also suitable for long-term storage and clinical translation due to its stability in biological media and its ability to be lyophilized. The study highlights the potential of NanoJagg as a versatile senoprobe for the detection of senescence in vivo, with applications in cancer therapy and other age-related diseases.A novel indocyanine green (ICG)-based nanoprobe, NanoJagg, was developed for in vivo detection of cellular senescence. NanoJagg is a biocompatible, injectable organic nanoprobe that selectively accumulates in senescent cells and is characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. The nanoprobe was synthesized through the self-assembly of ICG dimers under mild and scalable conditions, resulting in nanosized J-aggregate structures with high purity, physicochemical stability, and biocompatibility. NanoJagg was shown to be selectively taken up by senescent cells, accumulating in lysosomes, and exhibited a significant increase in fluorescence and PAT signals in senescent cells compared to non-senescent cells. The uptake of NanoJagg was found to be dependent on clathrin-mediated endocytosis and macropinocytosis. In vivo studies using tumor xenografts confirmed that NanoJagg could effectively detect chemotherapy-induced senescence, with a significant increase in signal in senescent tumors compared to control tumors. Additionally, NanoJagg was shown to be suitable for PAT imaging, providing high-resolution images of senescent cells with a strong PAT signal. The results demonstrate that NanoJagg is a promising tool for the detection and monitoring of senescence in various disease models, including cancer. The nanoprobe is also suitable for long-term storage and clinical translation due to its stability in biological media and its ability to be lyophilized. The study highlights the potential of NanoJagg as a versatile senoprobe for the detection of senescence in vivo, with applications in cancer therapy and other age-related diseases.