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3Application of laser-synthesized boron nanoparticles for boron
neutron capture therapy
A. Kasatova1'2*, K. Kuzmina2, I. Zelepukin3, K. Aiyyzhy4, E. Barmina14, A. Popov5, I. Razumov6, E. Zavjalov6, M. Grigoryeva1, S. Klimentov15, V. Ryabov1, S. Deyev35, A. Kabashin7,
S. Taskaev12, I. Zavestovskaya18
1-P.N. Lebedev Physical Institute of the Russian Academy of Sciences, Moscow 119991, Russia 2- Budker Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk
630090, Russia
3- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences,
Moscow 117997, Russia
4- A.M. Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow 119991, Russia 5- National Research Nuclear University MEPhI, Moscow 115409, Russia 6- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences,
Novosibirsk 630090, Russia 7- Aix-Marseille University, CNRS, LP3, Marseille13288, France 8- National Research Center "Kurchatov Institute", 1 Academician Kurchatov Square, Moscow 123182, Russia
Boron neutron capture therapy (BNCT) is a binary form of radiation therapy based on the selective destruction of cells of malignant tumors. The basic principle of BNCT is in the high ability of the non-radioactive 10B nucleus to absorb a thermal neutron, resulting in the reaction 10B(n,a)7Li, the products of which have a high deceleration rate and a short path length, thus the released energy of 2.79 MeV is limited by the size of one cell [1].
An important aspect of the successful implementation of BNCT in clinical practice is the development of targeted boron delivery drugs [2]. We investigated elemental boron nanoparticles (BNPs) fabricated using the methods of pulsed laser ablation in liquids as potential boron-containing agents for BNCT. Depending on the conditions (nanosecond and femtosecond pulses) of laser-ablative synthesis, the NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively, both coated with polyethylene glycol to improve their colloidal stability [3,4].
In in vitro experiments human tumor cell lines U87 (glioblastoma) and SW-620 (colorectal adenocarcinoma) were used. MTT-test and clonogenic assay did not show any cytotoxicity effects of BNPs up to 10B concentrations of 100 ^g/mL. The cells were preliminarily incubated with BNPs at a 10B concentration of 40 ^g/mL and were then irradiated with a thermal neutron beam at the accelerator-based neutron source at the Budker Institute of Nuclear Physics [5] for 30 min, providing the equivalent calculated dose of 8 Gy-Eq. Colony forming capacity of SW-620 cells dropped down to 12.6% for BNCT group previously incubated with a-BNPs and 1.6% for pc-BNPs BNCT group. Colony-forming capacity for U87 cells dropped down to 17%. The data is confirmed by MTT results.
For future BNCT in vivo, the boron biodistribution study was performed. Intratumoral administration of BNPs in immunodeficient SCID mice with subcutaneous U87 tumors demonstrated highest accumulation of boron in the tumor of 56 ^g/g and 82 ^g/g at 30 and 90 min after BNPs administration, respectively. The concentration of boron in the blood and in the surrounding normal tissue (skin and muscle) was statistically significantly lower, close to background values. Therefore, laser ablation of elemental boron powders and targets leads to the formation of spherical nanoparticles with a size of 20-50 nm. This technique provides the achieved boron content in the tumor, and the tumor/blood, tumor/ normal tissue boron concentration ratios is sufficient for successful BNCT in the case of boron enrichment with the therapeutically suitable isotope boron-10.
The research was supported by a grant from the Russian Science Foundation № 24-62-00018, https://rscf.ru/en/project/24-62-00018/.
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