A Bottom?Up Approach to Red?Emitting Molecular?Based Nanoparticles with Natural Stealth Properties and their Use for Single?Particle Tracking Deep in Brain Tissue

Fluorescent nanoparticles dedicated to bioimaging applications should possess specific properties that have be maintained in the aqueous, reactive, and crowded biological environment. These include chemical photostability, small size (on scale of subcellular structures), biocompatibility, high brightness, good solubility. The latter is a major challenge for inorganic nanoparticles, which require surface coating made water soluble. Molecular-based fluorescent organic (FONs) may prove promising, spontaneously water-soluble alternative, whose bottom-up design allows fine-tuning individual properties. Here, critical controlling interaction with cellular membranes addressed. This report on bright, size-tunable, red-emitting, naturally stealthy FONs do not use antifouling agents impede interactions membranes. As proof concept, single diffusing up 150 µm deep brain tissue are imaged tracked.