Dodecaborate-Encapsulated Extracellular Vesicles with Modification of Cell-Penetrating Peptides for Enhancing Macropinocytotic Cellular Uptake and Biological Activity in Boron Neutron Capture Therapy
Dodecaborate-Encapsulated Extracellular Vesicles with Modification of Cell-Penetrating Peptides for Enhancing Macropinocytotic Cellular Uptake and Biological Activity in Boron Neutron Capture Therapy
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用于增强巨胞饮细胞摄取及硼中子俘获治疗中生物活性的经细胞穿透肽修饰的十二硼酸盐包封细胞外囊泡
DOI：
10.1021/acs.molpharmaceut.1c00882
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发表时间：
2022-04-04
影响因子：
4.9
通讯作者：
Nakase, Ikuhiko
中科院分区：
文献类型：
--
作者：
Hirase, Shiori;Aoki, Ayako;Nakase, Ikuhiko
硼中子俘获疗法（BNCT）是一种癌症放射疗法。在BNCT中，当用低能热中子照射时，癌细胞对硼-10原子的内化通过产生α粒子和反冲锂-7核诱导细胞死亡。在这项研究中，我们的目的是构建外泌体[细胞外囊泡（EV）]为基础的药物输送技术在BNCT。由于其药学上的优势，如控制免疫反应和有效利用细胞间通讯，电动汽车是潜在的下一代药物输送载体。在这项研究中，我们成功地开发了多面体硼烷阴离子封装的EV与修改的十六寡精氨酸，这是一种细胞穿透肽，在EV膜上诱导肌动蛋白依赖的内吞途径，巨胞饮，这导致有效的细胞摄取和显着的癌细胞杀伤BNCT活性。具有功能肽的“盒”修饰的基于EV的递送系统的简单和创新技术将不仅适用于BNCT，而且适用于各种各样的治疗方法。
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 alpha particles and recoiling lithium-7 nuclei when irradiated with lowenergy 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.