Emerging strategies for labeling and tracking of extracellular vesicles

Extracellular vesicles (EVs) are cell-derived lipid bilayer-enclosed nanovesicles. EVs are emerging as keys for identifying molecular mechanisms by mediating intercellular communication. EVs allow the exchange of various components with neighboring and distant cells through the extracellular environment, thereby involving in various biological processes in both physiological and pathological conditions such as wound healing, immune response, and tumorigenesis. EVs are also growing rapidly as cargo carrier for their natural delivery properties. Development of bioinspired delivery nanoplatforms based on exosomes-like mimetics also showed potentials to overcome limitations of synthetic nanoparticles. EVs offer a window to multicomponent diagnosis and a tool for design therapeutics. However, for successful clinical translation of EVs, the understanding of in vivo behavior is essential. Advancements in molecular imaging enabled high-resolution in vivo tracking of EVs, providing valuable information regarding trafficking, biodistribution, cellular uptake and molecular mechanism of EVs. Recent studies have explored various methods for visualizing EVs, each imaging technique has certain strengths and limitations. Highly specific, sensitive and biocompatible labeling and tracking strategies still in demand in EV visualization. In this review, we summarized methods for labeling and tracking of EVs and discussed benefits and drawbacks for each method. Future novel imaging modalities and combined strategies will provide avenues for understanding EV behavior and accelerate their clinical translation.