RRC ID 71940
Author Hirase S, Aoki A, Hattori Y, Morimoto K, Noguchi K, Fujii I, Takatani-Nakase T, Futaki S, Kirihata M, Nakase I.
Title Dodecaborate-Encapsulated Extracellular Vesicles with Modification of Cell-Penetrating Peptides for Enhancing Macropinocytotic Cellular Uptake and Biological Activity in Boron Neutron Capture Therapy.
Journal Mol Pharm
Abstract Boron neutron capture therapy (BNCT) is a radiation therapy for cancer. In BNCT, the internalization of boron-10 atoms by cancer cells induces cell death through the generation of α particles and recoiling lithium-7 nuclei when irradiated with low-energy thermal neutrons. In this study, we aimed to construct exosomes [extracellular vesicles (EVs)]-based drug delivery technology in BNCT. Because of their pharmaceutical advantages, such as controlled immune responses and effective usage of cell-to-cell communication, EVs are potential next-generation drug delivery carriers. In this study, we successfully developed polyhedral borane anion-encapsulated EVs with modification of hexadeca oligoarginine, which is a cell-penetrating peptide, on the EV membrane to induce the actin-dependent endocytosis pathway, macropinocytosis, which leads to efficient cellular uptake and remarkable cancer cell-killing BNCT activity. The simple and innovative technology of the EV-based delivery system with "cassette" modification of functional peptides will be applicable not only for BNCT but also for a wide variety of therapeutic methodologies.
Volume 19(4)
Pages 1135-1145
Published 2022-4-4
DOI 10.1021/acs.molpharmaceut.1c00882
PMID 35298163
MeSH Boron Compounds Boron Neutron Capture Therapy* / methods Cell-Penetrating Peptides* Extracellular Vesicles* Neutrons
IF 4.321
Resource
Human and Animal Cells HeLa