Ultralong-Term Super-Resolution Tracking of Lysosomes in Brain Organoids by Near-Infrared Noble Metal Nanoclusters

To study lysosomes with an ultralong term, herein, noble-metal Au and Ag nanoclusters (MNCs) modified with biocompatible protein bovine serum albumin (BSA) called BSA–NCs were applied to image lysosomes under structured illumination microscopy (SIM). Compared with commercial lysosomal dyes, BSA–NCs exhibited remarkable anti-interference in pH fluctuation, excellent antiphotobleaching for ultralong-term lysosomal tracking, and impressive near-infrared fluorescence. The lysosomal events (i.e., fission, fusion, and kiss-and-run events) were observed with the BSA–NCs under SIM, as was the interplay between lysosomes and mitochondria leading to mitophagy. With their molecular-like properties and near-infrared fluorescence, BSA–Au NCs proved able to enter the internal cells of organoids and, for the first time, were applied to track subcellular lysosomal dynamics. The results not only demonstrate that MNCs are excellent tools for imaging organelles in living cells and organoids with super-resolution technology but also highlight new fields for using MNCs in ultralong-term bioimaging.