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

2018 ◽  
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.

scholarly journals Quality Management System Program of in Vitro/in Vivo Test Facility of Boron Neutron Capture Therapy at Kartini Research Reactor

2016 ◽  
Vol 1 (2) ◽  
pp. 108
Author(s):  
Widarto Widarto ◽  
Isman Mulyadi Tri Atmoko ◽  
Gede Sutresna Wijaya
Keyword(s):  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Research Reactor ◽  
Test Facility ◽  
Neutron Capture Therapy ◽  
In Vivo Test ◽  
Boron Neutron Capture ◽  
System Program

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<sup>-2</sup> s<sup>-1</sup>and  thermal neutron flux is 3,0691E+06 n cm<sup>-2</sup> s<sup>-1</sup>, 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

scholarly journals Boron neutron capture therapy in cancer: past, present and future

2007 ◽  
Vol 51 (5) ◽  
pp. 852-856 ◽  
Author(s):  
Mario A. Pisarev ◽  
Maria Alejandra Dagrosa ◽  
Guilermo J. Juvenal
Keyword(s):  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Alpha Particles ◽  
Neutron Capture Therapy ◽  
Selective Uptake ◽  
Complete Control ◽  
Boron Neutron Capture ◽  
A Cell ◽  
Undifferentiated Thyroid Cancer

Undifferentiated thyroid cancer (UTC) is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron non-radioactive compounds by a tumor, and the subsequent irradiation of the area with an appropriate neutron beam. 10B is then activated to 11B, which will immediately decay releasing alpha particles and 7Li, of high linear energy transfer (LET) and limited reach. Clinical trials are being performed in patients with glioblastoma multiforme and melanoma. We have explored its possible application to UTC. Our results demonstrated that a cell line of human UTC has a selective uptake of borophenylalanine (BPA) both in vitro and after transplantation to nude mice. Treatment of mice by BNCT led to a complete control of growth and cure of 100% of the animals. Moreover dogs with spontaneous UTC also have a selective uptake of BPA. At the present we are studying the biodistribution of BPA in patients with UTC before its application in humans.

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.

scholarly journals 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

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

<span>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 </span><em>Monte Carlo N-Particle Extended </em><span>(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.</span>

scholarly journals 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

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

<span>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.</span>

scholarly journals Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy

Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3337
Author(s):  
Sara Hooshmand ◽  
Sahar Mollazadeh ◽  
Negar Akrami ◽  
Mehrnoosh Ghanad ◽  
Ahmed El-Fiqi ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Skin Regeneration ◽  
Bioactive Molecules ◽  
Wound Management ◽  
Bioactive Glasses ◽  
Wide Range

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.

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