A novel10B-enriched carboranyl-containing phthalocyanine as a radio- and photo-sensitising agent for boron neutron capture therapy and photodynamic therapy of tumours: in vitro and in vivo studies

The quality manajement system program of in vitro / in vivo test facility of Boron Neutron Capture Therapy (BNCT) methode as quality assurance requirement for utilization of radial pearcing beamport of Kartini research have been done. Identification and management of technical specification and parameters meassurement of to the radial piercing beamport have been determined for preparing in vitro / in vivo test facility. The parameters are epithermal neutron flux is 9,8243E+05 n cm-2 s-1and thermal neutron flux is 3,0691E+06 n cm-2 s-1, radiation shielding of parafin, dimension and size of piercing radial and instrumentatin and control system for automatic transfer of in vitro / in vivo samplels have been documented. Management system of the documents for fullfil basic guidance to perform working job of in vitro / in vivo at the piercing radial beamport of Kartini Research Reactor in order purpose utilization of the reactor for safety worker of the radiation area, society and invironment beeing safely

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Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

10.1101/471128 ◽

2018 ◽

Cited By ~ 1

Author(s):

Guillaume Vares ◽

Vincent Jallet ◽

Yoshitaka Matsumoto ◽

Cedric Rentier ◽

Kentaro Takayama ◽

...

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Mesoporous Silica Nanoparticles ◽

Alpha Particles ◽

Neutron Capture Therapy ◽

Boron Neutron Capture

AbstractTreatment resistance, relapse and metastasis remain critical issues in some challenging cancers, such as chondrosarcomas. Boron-neutron Capture Therapy (BNCT) is a targeted radiation therapy modality that relies on the ability of boron atoms to capture low energy neutrons, yielding high linear energy transfer alpha particles. We have developed an innovative boron-delivery system for BNCT, composed of multifunctional fluorescent mesoporous silica nanoparticles (B-MSNs), grafted with an activatable cell penetrating peptide (ACPP) for improved penetration in tumors and with Gadolinium for magnetic resonance imaging (MRI)in vivo. Chondrosarcoma cells were exposedin vitroto an epithermal neutron beam after B-MSNs administration. BNCT beam exposure successfully induced DNA damage and cell death, including in radio-resistant ALDH+ cancer stem cells (CSCs), suggesting that BNCT using this system might be a suitable treatment modality for chondrosarcoma or other hard-to-treat cancers.

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

Biomedicines ◽

10.3390/biomedicines9010074 ◽

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.

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Optimization of Neutron Collimator in The Thermal Column of Kartini Research Reactor for in vitro and in vivo Trials Facility of Boron Neutron Capture Therapy using MCNP-X Simulator

Indonesian Journal of Physics and Nuclear Applications ◽

10.24246/ijpna.v1i1.54-62 ◽

2016 ◽

Vol 1 (1) ◽

pp. 54

Author(s):

Ranti Warfi ◽

Andang Widi Harto ◽

Yohannes Sardjono ◽

Widarto Widarto

Keyword(s):

Neutron Beam ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Epithermal Neutron ◽

Research Reactor ◽

Neutron Capture Therapy ◽

Boron Neutron Capture ◽

Thermal Column

The optimization of thermal column collimator has been studied which resulted epithermal neutron beam for in vivo and in vitro trials of Boron Neutron Capture Therapy (BNCT) at Kartini Research Reactor of 100 kW by means of Monte Carlo N-Particle Extended (MCNP-X) codes. The design criteria were based on recommendation from the International Atomic Energy Agency (IAEA). MCNP-X calculations indicated by using 5 cm thickness of Ni as collimator wall, 30 cm thickness of Al as moderator, 20 cm thickness of 60Ni as filter, 2 cm thickness of Bi as γ-ray shielding, 3 cm thickness of 6Li2CO3-polyethylene as beam delimiter, and for in vivo in vitro trials purpose, aperture was designed 8 cm radius size, an epitermal neutron beam with an intensity 1.13E+09 n.cm-2.s-1, fast neutron and γ-doses per epithermal neutron of 1.76E-13 Gy.cm2.n-1 and 1.45E-13Gy.cm2.n-1,minimum thermal neutron per epithermal neutron ratio of 0.008,and maximum directionality of 0.73, respectively could be produced. The results have passed all the IAEA’s criteria.

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Dosimetry of in vitro and in vivo Trials in Thermal Column Kartini Reactor for Boron Neutron Capture Therapy (BNCT) facility by using MCNPX Simulator Code

Indonesian Journal of Physics and Nuclear Applications ◽

10.24246/ijpna.v1i2.63-72 ◽

2016 ◽

Vol 1 (2) ◽

pp. 63

Author(s):

Adrian Tesalonika ◽

Andang Widi Harto ◽

Yohannes Sardjono ◽

Isman Mulyadi Triatmoko

Keyword(s):

Dose Rate ◽

Exposure Time ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Neutron Capture Therapy ◽

Boron Neutron Capture ◽

Thermal Column ◽

Tissue Material

A dosimetry study of in vitro and in vivo trials system in thermal column of Kartini Reactor for Boron Neutron Capture Therapy (BNCT) facility has been conducted by using the Monte Carlo N-Particle Extended (MCNPX) software. Source of neutron originated from the 100 kW reactor which has been modified by the previous researcher. Models have been made by using simple geometries to represent tissues. Models of in vitro have been made by 4 spheres each has 1 cm diameter to represent tumour, whereas in vivo by 4 cylinders each has 6 cm length, 3 cm diameter, and breast soft tissue material with 1 cm sphere each located in the center of the cylinders to represent models of mouse with tumour. An increase in value of the boron concentration will increase the value of dose rate as well, then the exposure time should be shorter. The exposure times (in minutes) of in vitro trials for 20, 25, 30, 50, 75, 100, 125, and 150 μg boron/g tissues are 117.77, 117.77, 117.07, 115.69, 114.02, 112.39, 110.80, and 109.27. Whereas the exposure times of in vivo trials are 163.58, 162.78, 161.98, 158.88, 155.16, 151.61, 148.22, dan 144.98. In vitro trials have greater values of dose rate so that in vitro trials have shorter exposure time.

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

Molecules ◽

10.3390/molecules24193609 ◽

2019 ◽

Vol 24 (19) ◽

pp. 3609 ◽

Cited By ~ 6

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.

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