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Open AccessArticle

Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation

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Radiochemistry and Nuclear Imaging Group, CIC biomaGUNE, 20014 San Sebastian, Spain
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Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06511, USA
3
Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA
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Radiochemistry Platform, CIC biomaGUNE, 20014 San Sebastian, Spain
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Institute of Medical Physics and Biophysics, Leipzig University, Härtelstrasse 16-18, 04107 Leipzig, Germany
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Felix Bloch Institute for Solid State Physics, Leipzig University, Linnéstraße 5, 04103 Leipzig, Germany
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Radioimaging and Image Analysis Platform, CIC biomaGUNE, 20014 San Sebastian, Spain
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Centro de Investigación Biomédica en red Enfermedades Respiratorias–CIBERES, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Piotr Kaszyński
Molecules 2019, 24(19), 3609; https://doi.org/10.3390/molecules24193609
Received: 16 September 2019 / Accepted: 1 October 2019 / Published: 7 October 2019
(This article belongs to the Special Issue Advances in Materials Derived from Polyhedral Boron Clusters)
Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN ([email protected][4]) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ξ-potential of −18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. [email protected][4] could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the [email protected][4]. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies. View Full-Text
Keywords: boron neutron capture therapy; gold nanoparticles; cobalt bis(dicarbollide); positron emission tomography; radiolabelling; iodine-124; HT1080 boron neutron capture therapy; gold nanoparticles; cobalt bis(dicarbollide); positron emission tomography; radiolabelling; iodine-124; HT1080
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Pulagam, K.R.; Gona, K.B.; Gómez-Vallejo, V.; Meijer, J.; Zilberfain, C.; Estrela-Lopis, I.; Baz, Z.; Cossío, U.; Llop, J. Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation. Molecules 2019, 24, 3609.

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