scholarly journals Therapeutic Pretargeting with Gold Nanoparticles as Drug Candidates for Boron Neutron Capture Therapy

2020 ◽  
Vol 37 (12) ◽  
pp. 2000200 ◽  
Author(s):  
Irene V. J. Feiner ◽  
Krishna R. Pulagam ◽  
Vanessa Gómez‐Vallejo ◽  
Kepa Zamacola ◽  
Zuriñe Baz ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Drug Candidates ◽  
Boron Neutron Capture

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

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3609 ◽  
Author(s):  
Pulagam ◽  
Gona ◽  
Gómez-Vallejo ◽  
Meijer ◽  
Zilberfain ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Mouse Model ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
The Core ◽  
Boron Neutron Capture ◽  
Biodistribution Studies ◽  
Imaging Results

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.

scholarly journals Rational Design of Albumin Theranostic Conjugates for Gold Nanoparticles Anticancer Drugs: Where the Seed Meets the Soil?

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 74
Author(s):  
Tatyana V. Popova ◽  
Inna A. Pyshnaya ◽  
Olga D. Zakharova ◽  
Andrey E. Akulov ◽  
Oleg B. Shevelev ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Rational Design ◽  
Chemotherapeutic Agents ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture ◽  
Theranostic Agents

Multifunctional gold nanoparticles (AuNPs) may serve as a scaffold to integrate diagnostic and therapeutic functions into one theranostic system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. Herein, albumin-AuNP theranostic agents have been obtained by conjugation of an anticancer nucleotide trifluorothymidine (TFT) or a boron-neutron capture therapy drug undecahydro-closo-dodecaborate (B12H12) to bimodal human serum albumin (HSA) followed by reacting of the albumin conjugates with AuNPs. In vitro studies have revealed a stronger cytotoxicity by the AuNPs decorated with the TFT-tagged bimodal HSA than by the boronated albumin conjugates. Despite long circulation time, lack of the significant accumulation in the tumor was observed for the AuNP theranostic conjugates. Our unique labelling strategy allows for monitoring of spatial distribution of the AuNPs theranostic in vivo in real time with high sensitivity, thus reducing the number of animals required for testing and optimizing new nanosystems as chemotherapeutic agents and boron-neutron capture therapy drug candidates.

Rational design of gold nanoparticles functionalized with carboranes for application in Boron Neutron Capture Therapy

2013 ◽  
Vol 458 (2) ◽  
pp. 340-346 ◽  
Author(s):  
Laura Ciani ◽  
Silva Bortolussi ◽  
Ian Postuma ◽  
Laura Cansolino ◽  
Cinzia Ferrari ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Rational Design ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture

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

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1490
Author(s):  
Alexander Zaboronok ◽  
Sergey Taskaev ◽  
Olga Volkova ◽  
Ludmila Mechetina ◽  
Anna Kasatova ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Tumor Cells ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Malignant Tumors ◽  
Absorbed Dose ◽  
Alpha Particles ◽  
Neutron Capture Therapy ◽  
Linear Quadratic ◽  
Boron Neutron Capture

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.

scholarly journals HGG-05. REGRESSION OF RECURRENT GLIOBLASTOMA AFTER BORON NEUTRON CAPTURE THERAPY AND CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IN A CHILD

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii345-iii345
Author(s):  
Hsin-Hung Chen ◽  
Yi-Wei Chen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Antigen Receptor ◽  
Neutron Capture Therapy ◽  
T Cell Therapy ◽  
Boron Neutron Capture ◽  
Car T

Abstract A 6 y/o girl with recurrent multifocal glioblastoma received 3 times of boron neutron capture therapy (BNCT) and chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen HER2. Multiple infusions of CAR T cells were administered over 30 days through intraventricular delivery routes. It was not associated with any toxic effects of grade 3 or higher. After BNCT and CAR T-cell treatment, regression of all existing intracranial lesions were observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid, but new lesions recurred soon after the treatment. This clinical response continued for 14 months after the initiation of first recurrence.

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