CEST MRI detection of Glycoengineered Extracellular Vesicles

Motivation: Extracellular vesicles (EVs) are innovative carriers for drug and gene delivery, yet current imaging relies on fluorescent, metallic, or isotopic labels, complicating clinical translation. Metabolic glycoengineering (MGE) may enhance EV targeting naturally by incorporating non-natural sugars into EV surfaces. Goal(s): To leverage CEST MRI for non-labeled detection of MGE-EVs in vivo. To examine MGE's impact on EV properties and optimize non-natural glycan selection. Approach: MGE incorporates non-natural monosaccharides into EV surfaces, creating a profile suitable for CEST MRI-based visualization. Results: In vitro and in vivo studies validate MGE-EVs as innovative theranostic platforms, with inherent imaging properties advancing clinical potential. Impact: Leveraging non-natural sugars as CEST MRI agents equips MGE-EVs with advanced MRI tracking capabilities. This innovation is poised to accelerate both preclinical development and clinical translation of more effective MGE-EV-based drug delivery vectors for a wide variety of diseases.