Extracellular Vesicles Comprising Carborane Prepared by a Host Exchanging Reaction as a Boron Carrier for Boron Neutron Capture Therapy

• DOI: 10.1021/acsami.4c07650
• Publication Date: 2024-08-06T18:38:21Z
• Authors: Riku Kawasaki; Ayano Oshige; Nanami Kono; Keita Yamana; Hidetoshi Hirano; Yamato Miura; Ryuji Yorioka; Kaori Bando; Anri Tabata; Naoki Yasukawa; Masahiro Sadakane; Yu Sanada; Minoru Suzuki; Takushi Takata; Yoshinori Sakurai; Hiroki Tanaka; Dilimulati Yimiti; Shigeru Miyaki; Nobuo Adachi; Ryosuke Mizuta; Yoshihiro Sasaki; Kazunari Akiyoshi; Yoshihide Hattori; Mitsunori Kirihata; Takeshi Nagasaki; Atsushi Ikeda
• Keywords: Carborane; Extracellular Vesicles

With their low immunogenicity and excellent deliverability, extracellular vesicles (EVs) are promising platforms for drug delivery systems. In this study, hydrophobic molecule loading techniques were developed via an exchange reaction based on supramolecular chemistry without using organic solvents that can induce EV disruption harmful side effects. To demonstrate the availability of exchanging to prepare drug-loading EVs, boron cluster carborane (CB) was introduced EVs (CB@EVs), which is expected as a agent neutron capture therapy (BNCT). The enabled encapsulation CB disrupting structure forming aggregates. Single-particle analysis revealed uniformly introduce cargo molecules advantageous in formulating pharmaceuticals. performance CB@EVs agents BNCT demonstrated vitro vivo. Compared L-BPA, clinically available agent, delivered with liposomes, CB@EV systems exhibited highest activity due deliverability endocytosis-independent pathway. system deeply penetrate 3D cultured spheroids even presence matrices. EV-based could efficiently accumulate tumor tissues xenograft model mice high selectivity, mainly enhanced permeation retention effect, vivo therapeutic benefits compared L-BPA/fructose complex. All features also establishing anticancer platforms.