De Novo-Designed Near-Infrared Nanoaggregates for Super-Resolution Monitoring of Lysosomes in Cells, in Whole Organoids, and in Vivo.

As the cleaners of cells, lysosomes play an important role in circulating organic matter within cells, recovering damaged organelles, and removing waste via endocytosis. Because lysosome dysfunction is associated with various diseases-lysosomal storage diseases, inherited diseases, rheumatoid arthritis, and even shock-it is vital to monitor the movement of lysosomes in cells and in vivo. To that purpose, a method of optical imaging, super-resolution imaging technology (e.g., SIM and STORM), can overcome the limitations of traditional optical imaging and afford a range of possibilities for fluorescence imaging. However, the short wavelength excitation and easy photobleaching of super-resolution fluorescence probes somewhat problematize super-resolution imaging. As described herein, we designed a low-toxicity, photostable, near-infrared small molecule fluorescence probe HD-Br for use in the super-resolution imaging of lysosomes. The interaction of lysosomes and mitochondria was dynamically traced while using the probe's properties to label the lysosomes. Because the probe has the optimal near-infrared excitation and emission wavelengths, liver organoid 3D imaging and Caenorhabditis elegans imaging were also performed. Altogether, our findings indicate valuable approaches and techniques for super-resolution 3D and in vivo imaging.