Engineered Extracellular Vesicles with Compound-Induced Cargo Delivery to Solid Tumors

Abstract

Efficient delivery of functional factors into target cells remains challenging. Although extracellular vesicles (EVs) are considered to be potential therapeutic delivery vehicles, a variety of efficient therapeutic delivery tools are still needed for cancer cells. Herein, we demonstrated a promising method to deliver EVs to refractory cancer cells via a small molecule-induced trafficking system. We generated an inducible interaction system between the FKBP12-rapamycin-binding protein (FRB) domain and FK506 binding protein (FKBP) to deliver specific cargo to EVs. CD9, an abundant protein in EVs, was fused to the FRB domain, and the specific cargo to be delivered was linked to FKBP. Rapamycin recruited validated cargo to EVs through protein-protein interactions (PPIs), such as the FKBP-FRB interaction system. The released EVs were functionally delivered to refractory cancer cells, triple negative breast cancer cells, non-small cell lung cancer cells, and pancreatic cancer cells. Therefore, the functional delivery system driven by reversible PPIs may provide new possibilities for a therapeutic cure against refractory cancers.

Extracellular Vesicles as Delivery Vehicles for Non-Coding RNAs: Potential Biomarkers for Chronic Liver Diseases

“…Due to their biocompatibility, EVs have also been engineered to specifically deliver therapeutic cargo to cancer cells. For instance, Kim et al recently described a rapamycin-induced protein–protein interaction cargo delivery system to modify EVs by using the binding affinity between the FKBP12–rapamycin-binding protein (FRB) domain and FK506-binding protein (FKBP) [ 44 ]. These EVs were functionally delivered to recipient refractory cancer cells, indicating that this system is promising for the delivery of therapeutic cargo specifically to target cells.…”