Polymer-Stabilized Elemental Boron Nanoparticles for Boron Neutron Capture Therapy: Initial Irradiation Experiments

Abstract

Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation after a single injection has been partially solved by its continuous infusion; however, its lack of persistence has driven the development of new compounds that overcome the imperfections of BPA. We propose using elemental boron nanoparticles (eBNPs) synthesized by cascade ultrasonic dispersion and destruction of elemental boron microparticles and stabilized with hydroxyethylcellulose (HEC) as a core component of a novel boron drug for BNCT. These HEC particles are stable in aqueous media and show no apparent influence on U251, U87, and T98G human glioma cell proliferation without neutron beam irradiation. In BNCT experiments, cells incubated with eBNPs or BPA at an equivalent concentration of 40 µg 10B/mL for 24 h or control cells without boron were irradiated at an accelerator-based neutron source with a total fluence of thermal and epithermal neutrons of 2.685, 5.370, or 8.055 × 1012/cm2. The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linear-quadratic model and calculated radiobiological parameters, though the effect of both compounds differed depending on the cell line. The results of our study warrant further tumor targeting-oriented modifications of synthesized nanoparticles and subsequent in vivo BNCT experiments.

BPA‐Containing Polydopamine Nanoparticles for Boron Neutron Capture Therapy in a U87 Glioma Orthotopic Model

“…Although our results, based on a limited record, suggest that this strategy has achieved the desired outcome, there are still some problems with B‐PDA nanoparticles. Compared with the previous B‐10 enriched nanoparticles, [ 38–44 ] our nanoparticles have a lower boron content, which led to more particles being injected to meet the demand of BNCT. Moreover, the metabolism, degradation and clearance performance of B‐PDA nanoparticles were still determined, and the nanoparticle size was over 100 nm.…”

A Laser Synthesis Route to Boron‐Doped Gold Nanoparticles Designed for X‐Ray Radiotherapy and Boron Neutron Capture Therapy Assisted by CT Imaging

“…These results suggest that the coexistence of boron and gold at the nanoscale may be associated with higher cytotoxicity than PEG‐coated pure Au NPs, which were not‐cytotoxic up to concentrations of 100 µg mL −1 , [ 75 ] and pure B NPs also evidenced limited cytotoxicity up to 250 µg mL −1 . [ 76 ]…”

Study of Lithium Biodistribution and Nephrotoxicity in Skin Melanoma Mice Model: The First Step towards Implementing Lithium Neutron Capture Therapy

“…In addition, the best results of BNCT studies and high concentrations of boron in the tumor, have recently been obtained by using the latest generation of boron agents, which significantly increase the selectivity of its delivery to tumor cells. These results have been obtained by using various types of liposomes [ 22 , 23 ], polymers [ 24 ], nanoparticles [ 25 , 26 , 27 ], mannopyranoside complexes [ 28 ] and an electrochemotherapy in combination with boron drugs [ 29 ]. Here we used LC salt, which, upon administration of Li ions, were nonselectively absorbed by tumor cells; therefore, it can be assumed that the creation of a special construction with Li based on a selective carrier, similar to boron drugs, will significantly increase the accumulation of Li in the tumor.…”