Characterization of small intracellular vesicles uncovers their potential as drug carriers and therapeutic agents

Small extracellular vesicles (sEVs) have been extensively investigated as a source of clinically relevant cargo. Alongside the secretion of EVs, such as exosomes, cells house a multitude of internal vesicles involved in various physiologic processes and metabolic activities. Herein, we developed protocols to isolate small intracellular vesicles (sIVs) from different cell types and investigated their biological characteristics and potential therapeutic applications. SIVs are smaller in size, have higher yield, and display a markedly greater uptake in vitro and in vivo than sEVs. The composition of proteins, RNAs, and lipids of sIVs differed from that of sEVs. Additionally, sIVs derived from mesenchymal stem cells outperformed sEVs in ameliorating retinal degeneration by mitigating endoplasmic reticulum stress and providing neuroprotective factors in an in vivo model. This study identified a distinct functional intracellular nanoparticle as a suitable alternative to sEVs in clinical translation