5 research outputs found
Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation
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
Single cell study of adipose tissue mediated lipid droplet formation and biochemical alterations in breast cancer cells
Obesity is a known risk factor for breast cancer and a negative prognostic factor for cancer recurrence and survival. Several studies demonstrated that aggressive breast tumor cells contain higher numbers of intracellular lipid droplets (LDs). Here we applied simultaneous visualization, identification and quantification of the lipid accumulation in lipid droplets (LDs) of aggressive, human triple-negative MDA-MB-231 breast cancer cells treated with adipose tissue-conditioned medium (ACM) derived from overweight and obese patients. In addition to Oil Red O and AdipoRed fluorescent staining, label-free confocal Raman microspectroscopy (CRM) has been applied. CRM enables imaging of cell compartments as well as quantification and monitoring of specific biomolecules and metabolic processes on a single cell level. Interestingly, breast cancer cells incubated with ACM showed a significantly higher number of intracellular LDs. Cultivation of breast tumor cells with ACM of obese patients induced the formation of LDs with a 20-fold higher lipid concentration than cultivation with basal medium. This is in line with the significantly higher levels of NEFAs (non-esterified fatty acids) detected in the ACM obtained from obese patient compared to ACM obtained from overweight patients or basal medium. Further, by principal component analysis, we identified a significant increase in unsaturation, esterification and lipid to protein ratio in LDs in breast cancer cells incubated with ACM. CRM analyses might function as a valuable diagnostic tool to identify metabolic alterations in biological samples which in turn could provide more detailed insights in the pathogenesis of breast cancer in association with obesity
Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation
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 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. 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
Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation
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
Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In Vivo Evaluation
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