Boron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization.

Autor:	Popov AL; P. N. Lebedev Physical Institute of the Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia.; Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 3 Institutskaya St., Pushchino 142290, Russia., Kolmanovich DD; P. N. Lebedev Physical Institute of the Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia.; Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 3 Institutskaya St., Pushchino 142290, Russia., Chukavin NN; Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 3 Institutskaya St., Pushchino 142290, Russia., Zelepukin IV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.; Department of Medicinal Chemistry, Uppsala University, 75310 Uppsala, Sweden., Tikhonowski GV; Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University MEPhI, Kashirskoe Shosse 31, Moscow 115409, Russia., Pastukhov AI; LP3, CNRS, Aix-Marseille University, 13288 Marseille, France., Popov AA; Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University MEPhI, Kashirskoe Shosse 31, Moscow 115409, Russia., Shemyakov AE; P. N. Lebedev Physical Institute of the Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia., Klimentov SM; Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University MEPhI, Kashirskoe Shosse 31, Moscow 115409, Russia., Ryabov VA; P. N. Lebedev Physical Institute of the Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia., Deyev SM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.; Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University MEPhI, Kashirskoe Shosse 31, Moscow 115409, Russia.; National Research Center 'Kurchatov Institute', Academician Kurchatov Square 1, Moscow 123182, Russia.; 'Biomarker' Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., Kazan 420008, Russia.; Institute of Molecular Theranostics, Sechenov University, Moscow 119991, Russia., Zavestovskaya IN; P. N. Lebedev Physical Institute of the Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia.; Institute of Engineering Physics for Biomedicine (PhysBio), National Research Nuclear University MEPhI, Kashirskoe Shosse 31, Moscow 115409, Russia.; National Research Center 'Kurchatov Institute', Academician Kurchatov Square 1, Moscow 123182, Russia., Kabashin AV; LP3, CNRS, Aix-Marseille University, 13288 Marseille, France.
Jazyk:	angličtina
Zdroj:	Molecules (Basel, Switzerland) [Molecules] 2024 Aug 21; Vol. 29 (16). Date of Electronic Publication: 2024 Aug 21.
DOI:	10.3390/molecules29163936
Abstrakt:	Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy. Spherical B NPs with a mode size of 25 nm were prepared by methods of pulsed laser ablation in water, followed by their coating by polyethylene glycol to improve their colloidal stability in buffers. Then, we assessed the efficiency of B NPs as sensitizers of cancer cell killing under irradiation with a 160.5 MeV proton beam. Our experiments showed that the combined effect of B NPs and proton irradiation induces an increased level of superoxide anion radical generation, which leads to the depolarization of mitochondria, a drop in their membrane mitochondrial potential, and the development of apoptosis. A comprehensive gene expression analysis (via RT-PCR) confirmed increased overexpression of 52 genes (out of 87 studied) involved in the cell redox status and oxidative stress, compared to 12 genes in the cells irradiated without B NPs. Other possible mechanisms responsible for the B NPs-induced radiosensitizing effect, including one related to the generation of alpha particles, are discussed. The obtained results give a better insight into the processes involved in the boron-induced enhancement of proton therapy and enable one to optimize parameters of proton therapy in order to maximize therapeutic outcomes.
Databáze:	MEDLINE
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