Sang‐Yeob Kim

Exosomes are nano-sized membranous vesicles produced by nearly all types of cells. Since exosome-like vesicles are produced in an evolutionarily conserved manner for information and function transfer from the originating cells to recipient cells, an increasing number of studies have focused on their application as therapeutic agents, drug delivery vehicles, and diagnostic targets. Analysis of the in vivo distribution of exosomes is a prerequisite for the development of exosome-based therapeutics and drug delivery vehicles with accurate prediction of therapeutic dose and potential side effects. Various attempts to evaluate the biodistribution of exosomes obtained from different sources have been reported. In this review, we examined the current trends and the advantages and disadvantages of the methods used to determine the biodistribution of exosomes by molecular imaging. We also reviewed 29 publications to compare the methods employed to isolate, analyze, and label exosomes as well as to determine the biodistribution of labeled exosomes.

Recent technological advances have expanded fluorescence (FL) imaging into the second near-infrared region (NIR-II; wavelength = 1000-1700 nm), providing high spatial resolution through deep tissues. However, bright and compact fluorophores are rare in this region, and sophisticated control over NIR-II probes has not been fully achieved yet. Herein, we report an enzyme-activatable NIR-II probe that exhibits FL upon matrix metalloprotease activity in tumor microenvironment. Bright and stable PbS/CdS/ZnS core/shell/shell quantum dots (QDs) were synthesized as a model NIR-II fluorophore, and activatable modulators were attached to exploit photoexcited electron transfer (PET) quenching. The quasi type-II QD band alignment allowed rapid and effective FL modulations with the compact surface ligand modulator that contains methylene blue PET quencher. The modulator was optimized to afford full enzyme accessibility and high activation signal surge upon the enzyme activity. Using a colon cancer mouse model, the probe demonstrated selective FL activation at tumor sites with 3-fold signal enhancement in 10 min. Optical phantom experiments confirmed the advantages of the NIR-II probe over conventional dyes in the first near-infrared region.