Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications

Abstract

Inorganic nanoparticles of boron-rich compounds represent an attractive alternative to boron-containing molecules, such as boronophenylalanine or boranes, for BNCT applications. This work describes the synthesis and biological activity of multifunctional boron carbide nanoparticles stabilized with polyacrylic acid (PAA) and a gadolinium (Gd)-rich solid phase. A fluorophore (DiI) was included in the PAA functionalization, allowing the confocal microscopy imaging of the nanoparticles. Analysis of the interaction and activity of these fluorescent Gd-containing B4C nanoparticles (FGdBNPs) with cultured cells was appraised using an innovative correlative microscopy approach combining intracellular neutron autoradiography, confocal, and SEM imaging. This new approach allows visualizing the cells, the FGdBNP, and the events deriving from the nuclear process in the same image. Quantification of 10B by neutron autoradiography in cells treated with FGdBNPs confirmed a significant accumulation of NPs with low levels of cellular toxicity. These results suggest that these NPs might represent a valuable tool for achieving a high boron concentration in tumoral cells.

Synthesis and Characterization of B4C-Based Multifunctional Nanoparticles for Boron Neutron Capture Therapy Applications

“…No peaks of the boron carbide phase can be observed, probably because of the shielding from the iron oxide NPs, which are heavier and with a higher concentration than B 4 C. The average crystallite size was calculated using the Debye Scherrer equation applied on (220), (311), and (400) peaks, and was found to be 3.7(0.4) nm. This crystallite size agrees with the TEM images, which show spherical, ultrasmall iron oxide NPs with diameters ranging from 4 nm to 6 nm, with an outer layer probably constituting the poorly crystalline region [28]. TEM also confirmed the successful co-localization of SPIONs and B 4 C NPs, as the latter seem to be surrounded by the ultrasmall SPION, and no bare B 4 C NPs are observed in the sample (Figure 2B).…”

“…Furthermore, boron carbide exhibits exceptional chemical inertness and high biocompatibility [23,24]. B 4 C NPs have already been investigated as possible 10 B carriers for BNCT [25][26][27][28][29]. The primary challenge associated with the use of B 4 C NPs is related to their inherent hydrophobicity and low chemical reactivity, posing obstacles to achieving effective chemical functionalization.…”

Gadolinium Neutron Capture Therapy for Cats and Dogs with Spontaneous Tumors Using Gd-DTPA

“…It has been employed in phase II clinical trials in patients with brain metastases and in phase I trials in patients with glioblastoma, lung, cervical, and pancreatic cancer [61]. Other newly synthesized gadolinium nanoparticles have recently been introduced, and further development of GdNCT is in progress [62,63].…”