Aptamer-conjugated extracellular nanovesicles for targeted drug delivery

Extracellular nanovesicles (ENV) released by many cells contain lipids, proteins, and nucleic acids that contribute to intercellular communication. ENVs have emerged as biomarkers and therapeutic targets but they have also been explored as drug delivery vehicles. However, for the latter application, clinical translation has been limited by low yield and inadequate targeting effects. ENV vectors with desired targeting properties can be produced from parental cells engineered to express membrane-bound targeting ligands, or they can be generated by fusion with targeting liposomes; however, neither approach has met clinical requirements. In this study, we demonstrate that mechanical extrusion of approximately 10⁷ cells grafted with lipidated ligands can generate cancer cell–targeting ENV and can be prepared in approximately 1 hour. This rapid and economic approach could pave the way for clinical implementation in the future. Significance: A new and rapid method for production of drug-targeting nanovesicles has implications for cancer treatment by chimeric antigen receptor T cells and other therapies.