Modification Technology for Exosome Membranes using Membrane-Curvature-Sensing Peptides and Its Application to Boron Neutron Capture Therapy.

Extracellular vesicles such as exosomes are expected to be used as drug delivery vehicles, particularly in personalized medicine, due to their pharmacological advantages. However, the development of functionalization techniques for isolated extracellular vesicles-including improving their intracellular uptake efficacy from the perspective of a drug delivery system and targeting disease-associated cells to reduce side effects-has become an urgent priority. The aim of this study was to develop a technology for modifying the surface of exosome membranes with functional molecules using membrane-curvature-sensing peptides. By using a cassette-based approach to modify the surface of exosomes with functional peptides that induce macropinocytosis, this technology achieved highly efficient intracellular delivery of exosomes. Furthermore, we applied this technology to boron neutron capture therapy (BNCT). By encapsulating therapeutic boron agents within exosomes, effective induction of cancer cell death through thermal neutron irradiation in BNCT was achieved.