The emergence of multiple particle tracking in intracellular trafficking of nanomedicines

A growing number of nanoparticle systems, termed "nanomedicines", are being developed for diagnostic and therapeutic applications. Nanoparticles can employ various cellular entry pathways and trafficking mechanisms to effectively deliver drugs, biomolecules, and imaging agents to precise sub-cellular locations. However, the dynamic transport of nanoparticles through the complex intracellular environment is not well understood, having been primarily studied with static or bulk averaged methods in the past. Such techniques do not provide detailed information regarding the transport mechanism and rates of individual nanoparticles, where understanding of the interaction of nanoparticles with the cellular environment remains incomplete. Recent advances in live-cell fluorescence microscopy and real-time multiple particle tracking (MPT) have facilitated an improved understanding of cell trafficking pathways. Understanding the dynamic transport of nanoparticles as they are delivered into complex cellular components may lead to rational improvements in the design of nanomedicines. This review discusses different cellular uptake and trafficking pathways of nanomedicines, briefly highlights current fluorescence microscopy tools, and provides examples from the recent literature on the use of MPT and its applications.