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 (PEG-AuNPs@[4])
with hydrodynamic diameter of 37.8 0.5 nm, core diameter of 19.2 1.4 nm and -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. PEG-AuNPs@[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 PEG-AuNPs@[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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84654 |
| Date | 11 April 2023 |
| Creators | Pulagam, Krishna R., Gona, Kiran B., Gómez-Vallejo, Vanessa, Meijer, Jan, Zilberfain, Carolin, Estrela-Lopis, Irina, Baz, Zuriñe, Cossío, Unai, Llop, Jordi |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1420-3049, 3609 |
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