title: Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.
abstract: A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance.
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan.
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Horiguchi
authors.affiliation: Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakai
authors.affiliation: Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-nishi 2-1010, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Asashiro-nishi 2-1010, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan; Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan. Electronic address: yukio@nagalabo.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000818:Animals; D001895:Boron / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects / Q000379:methods*; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D007554:Isotopes / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000517:prevention & control*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D007554:Isotopes; D019275:Radiopharmaceuticals; D017382:Reactive Oxygen Species; D001895:Boron
keywords: Adverse effect suppression; Boron cluster-containing redox nanoparticles; Boron neutron capture therapy; Drug delivery system; ROS scavenging