Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors

Abstract

Boron neutron capture therapy (BNCT) is an anticancer modality realized through 10B accumulation in tumor cells, neutron irradiation of the tumor, and decay of boron atoms with the release of alpha-particles and lithium nuclei that damage tumor cell DNA. As high-LET particle release takes place inside tumor cells absorbed dose calculations are difficult, since no essential extracellular energy is emitted. We placed gold nanoparticles inside tumor cells saturated with boron to more accurately measure the absorbed dose. T98G cells accumulated ~50 nm gold nanoparticles (AuNPs, 50 µg gold/mL) and boron-phenylalanine (BPA, 10, 20, 40 µg boron-10/mL), and were irradiated with a neutron flux of 3 × 108 cm−2s−1. Gamma-rays (411 keV) emitted by AuNPs in the cells were measured by a spectrometer and the absorbed dose was calculated using the formula D = (k × N × n)/m, where D was the absorbed dose (GyE), k—depth-related irradiation coefficient, N—number of activated gold atoms, n—boron concentration (ppm), and m—the mass of gold (g). Cell survival curves were fit to the linear-quadratic (LQ) model. We found no influence from the presence of the AuNPs on BNCT efficiency. Our approach will lead to further development of combined boron and high-Z element-containing compounds, and to further adaptation of isotope scanning for BNCT dosimetry.

Dose-Dependent Suppression of Human Glioblastoma Xenograft Growth by Accelerator-Based Boron Neutron Capture Therapy with Simultaneous Use of Two Boron-Containing Compounds

“…In order to develop new protocols to establish clinical-scale trials, the optimization of both compound and neutron beams are especially important in light of this shift away from reactor-based sources. We believe that, based on the results of previous trials at nuclear reactors and accelerator-based neutron sources by other research groups [ 2 , 3 , 4 , 5 , 43 , 53 , 54 ], as well as our own data [ 19 , 21 , 22 , 23 , 24 , 26 , 50 , 55 ], biodistribution of boron-containing compounds with regard to accelerator-based neutron sources is the current and well-reported future of BNCT [ 26 , 43 ]. It was thus necessary to continue the selection of optimal conditions for such experiments.…”

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

“…Fourteen days after irradiation, the cells were washed with PBS, fixed with glutaraldehyde, and stained with crystal violet. The dishes were scanned and the colonies (≥50 cells) were counted [48,58].…”

“…Based on the number of colonies, cell survival curves were plotted as a function of neutron fluence and fit to the linear-quadratic (LQ) model using the equation SF = e −(αC+βC 2 ) , where SF was the surviving fraction [59,60]. Radiobiological parameters α (alpha) and β (beta) were calculated from the cell survival curve fits in Microsoft Excel with the SOLVER add-on (Microsoft, Inc., Redmond, WA, USA) [58,61]. Differences in survival fractions between the cells irradiated with eBNPs, BPA, or without boron were evaluated by comparing the corresponding areas under the fitted curves (AUCs), which corresponded to the definite integrals of the LQ function with the fluence (F) range as a function of x [58,61]:…”

Packaging and Delivery of Asthma Therapeutics

“…Studying the effect of nanoparticles with incorporated active ingredients for the treatment of asthma, just as with liposomes, allows new vectors for delivery technology. In contrast to other areas of biology and medicine, such as oncology and radiology, where metallic nanoparticles (particularly gold) enhance therapeutic effect and diagnosis, the systemic absorption of these in long-term asthma use leads to side effects and thus emphasizes the use of biodegradable, non-metallic nanoparticles [133][134][135]. Lee at al.…”