Yoneoka Shuichiro, Nakagawa Yasuhiro, Uto Koichiro, Sakura Kazuma, Tsukahara Takehiko, Ebara Mitsuhiro
Laboratory for Advanced Nuclear Energy, Tokyo Institute of Technology, Tokyo, Japan.
International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, Japan.
Sci Technol Adv Mater. 2019 Mar 29;20(1):291-304. doi: 10.1080/14686996.2019.1586051. eCollection 2019.
Combining immunotherapeutic and radiotherapeutic technique has recently attracted much attention for advancing cancer treatment. If boron-incorporated hemagglutinating virus of Japan-envelope (HVJ-E) having high membrane fusion ability can be used as a boron delivery agent in boron neutron capture therapy (BNCT), a radical synergistic improvement of boron accumulation efficiency into tumor cells and antitumor immunity may be induced. In this study, we aimed to develop novel boron-containing biocompatible polymers modified onto HVJ-E surfaces. The copolymer consisting of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylamide benzoxaborole (MAAmBO), poly[MPC--MAAmBO], was successfully synthesized by using a simple free radical polymerization. The molecular structures and molecular weight of the poly[MPC--MAAmBO] copolymer were characterized by nuclear magnetic resonance and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, respectively. The poly[MPC--MAAmBO] was coated onto the HVJ-E surface via the chemical bonding between the MAAmBO moiety and the sugar moiety of HVJ-E. DLS, AFM, UV-Vis, and fluorescence measurements clarified that the size of the poly[MPC--MAAmBO]-coated HVJ-E, HVJ-E/p[MPC-MAAmBO], to be about 130 ~ 150 nm in diameter, and that the polymer having 9.82 × 10 boron atoms was steadily coated on a single HVJ-E particle. Moreover, cellular uptake of poly[MPC--MAAmBO] could be demonstrated without cytotoxicity, and the hemolysis could be successfully suppressed by 20%. These results indicate that the HVJ-E/p[MPC-MAAmBO] may be used as boron nanocarriers in a combination of immunotherapy with BNCT.
结合免疫治疗和放射治疗技术最近在推进癌症治疗方面备受关注。如果具有高膜融合能力的含硼日本血凝病毒包膜（HVJ-E）能够用作硼中子俘获疗法（BNCT）中的硼递送剂，那么可能会诱导肿瘤细胞中硼积累效率和抗肿瘤免疫力的显著协同提高。在本研究中，我们旨在开发修饰在HVJ-E表面的新型含硼生物相容性聚合物。通过简单的自由基聚合成功合成了由2-甲基丙烯酰氧基乙基磷酰胆碱（MPC）和甲基丙烯酰胺苯并硼氧六环（MAAmBO）组成的共聚物聚[MPC-MAAmBO]。聚[MPC-MAAmBO]共聚物的分子结构和分子量分别通过核磁共振和基质辅助激光解吸电离飞行时间质谱进行表征。通过MAAmBO部分与HVJ-E的糖部分之间的化学键合，将聚[MPC-MAAmBO]包被在HVJ-E表面。动态光散射（DLS）、原子力显微镜（AFM）、紫外可见光谱（UV-Vis）和荧光测量表明，聚[MPC-MAAmBO]包被的HVJ-E（HVJ-E/p[MPC-MAAmBO]）的直径约为130至150nm，并且具有9.82×10个硼原子的聚合物稳定地包被在单个HVJ-E颗粒上。此外，可以证明聚[MPC-MAAmBO]的细胞摄取没有细胞毒性，并且溶血可成功抑制20%。这些结果表明，HVJ-E/p[MPC-MAAmBO]可作为免疫疗法与BNCT联合使用的硼纳米载体。
