Boron phenyl alanine targeted ionic liquid decorated chitosan nanoparticles for mitoxantrone delivery to glioma cell line.

Nanotechnology has revolutionized drug delivery in cancer treatment. In this study, novel efficient pH-responsive boron phenylalanine (BPA) targeted nanoparticles (NPs) based on ionic liquid modified chitosan have been introduced for selective mitoxantrone (MTO) delivery to the U87MG glioma cells. Urocanic acid (UA) and imidazolium (Im) based ionic liquids were used for structural modification simultaneously. The NPs were prepared by ionic gelation and fully characterized; the pH-responding and swelling index of NPs were studied carefully. The drug release was studied at a pH of 5.5 in comparison to the neutral state. Also, the cytotoxicity of loaded NPs was evaluated on U87MG glial cells, and cellular uptake was studied. The NPs were smaller than 250 nm, with a spherical pattern and acceptable uniformity with a zeta potential around +20 mV. The loading efficacy was about 85%, and most of the loaded MTO released at a pH of 5.5 after 48 h with a swelling-controlled mechanism. The NPs showed a relatively lower IC50 than the free MTO, and the BPA-targeted NPs have lower IC50 and better cellular uptake than non-targeted NPs in U87MG cells. More studies on this promising formula are on the way, and the results will be published soon.

Evaluation of effectiveness of equivalent dose during proton boron fusion therapy (PBFT) for brain cancer: A Monte Carlo study.

Recently it has been suggested that the presence of boron-11 during proton therapy leads to a significant dose increasement in the BUR. Three high-LET alpha particles with an average energy of 4 MeV are generated at the point of interaction between proton and boron-11. Nevertheless, the cross-section of p+B11→3α interaction is negligible and dose increasement is unlikely. The purpose of this study is dose evaluation of the proton therapy with and without the boron-11. All simulations were performed using MCNPX 2.6.0 code at the Snyder head phantom. At the elderly stage, the range of Bragg-peaks was adapted to the tumor volume, with and without boron-11. Then, the different concentrations of boron-11 were assumed including 65,500,103,105,2.5×105 and 5×105ppm in the tumor region. To investigate the maximum effectiveness of PBFT (proton boron fusion therapy), the entire tumor was assumed full of boron-11, and the dose components were calculated. Consequently, In the best case, the maximum dose amplification was less than 5%, in which the entire tumor was assumed full boron-11. The total number of alpha particles generated from p+B11→3α interaction is negligible. As well as the presence of boron-11 during the proton therapy makes that the Bragg-peaks happen in greater depth. Hence, from the Monte Carlo standpoint, the effectiveness of the proton boron fusion therapy is not related to the alpha particles because the dose component of alpha particles is negligible.

Boron phenyl alanine targeted chitosan-PNIPAAm core-shell thermo-responsive nanoparticles: boosting drug delivery to glioblastoma in BNCT.

Boron neutron capture therapy (BNCT) is one of the best treatment modalities for glioblastoma multiform that could selectively kill the tumor cells. To be successful in BNCT, it is crucial to have enough 10B in the tumor. l-boron phenylalanine (l-BPA) targeted thermo-responsive core-shell nanoparticles (NPs) of chitosan-poly(N-isopropylacrylamide) (PNIPAAm) were our idea for endocytosis via sialic acid receptors, and selective delivery of 10B to glial cells. Methotrexate (MTX) was chosen as a model drug for evaluating the efficacy of NPs in tumor cells, and BPA was selected for BNCT purposes. The polymeric conjugates were synthesized and the chemical structures were approved by spectroscopic methods (FTIR, 1H NMR, and 11B NMR). Cargos were loaded efficiently (>95%) in the prepared NPs, and the release profile of MTX and BPA was studied around the lower critical solution temperature (LCST; about 39 °C). The loaded drugs were released quantitatively at the LCST, while almost no drug was released at 37 °C. The prepared NPs did not show considerable hemolysis ratio (<2%) and were still safe when loaded BPA, on U87MG cells. The MTX loaded NPs showed lower IC50 (30.78 µg/mL) than the free MTX (37.03 µg/mL) in MTT assay, and targeted NPs had the lowest IC50s in U87MG cell lines (27.35 µg/mL). Targeted BPA@CSSU-PNI NPs were uptaken better than the non-targeted ones by U87MG cells, and CR-39 assay showed the boron content efficiency for further applications in BNCT. This study's results introduce novel targeted thermo-responsive NPs for treating glioblastoma using BNCT.

Investigation of deep-seated brain tumor treatment based on Tehran research reactor new boron neutron capture therapy facility.

AIM: The main objective of this study is to evaluate the new proposed boron neutron capture therapy (BNCT) neutron beam based on the use of Tehran Research Reactor medical room to treat deep-seated brain tumors. MATERIAL AND METHODS: The Snyder head phantom has been simulated through the MCNPX Monte Carlo code to calculate different dose profiles and desired medical merits. The simulation consists of the full geometry of new beamline and the phantom. RESULTS: The medical merits related to the new proposed BNCT beamline have a good agreement with other facilities, which indicates the potential use of this new beam for treatment of deep-seated brain tumors. CONCLUSION: The obtained results show the capability of the new setup to treat deep-seated brain tumor, which was located up to ~5 cm of the skin surface.

Analysis of the caregiver effective dose during I-131 therapy of thyroid.

AIMS: The main objective of the present research is to analyze the caregiver effective dose during I-131 therapy of thyroid in some different situations using MCNP4C Monte Carlo code. PATIENTS AND METHODS: Two separate whole body Medical Internal Radiation Dosimetry (MIRD) phantoms have been defined simultaneously in a single Monte Carlo N-Particle (MCNP) input file as the patient and the caregiver. Two different groups of irradiation situations have been assumed for the caregiver related to the patient, (1) both the patient and the caregiver are standing and (2) the patient is lying in the bed while the caregiver is standing beside the patient. RESULTS: The results show that the caregiver effective dose is highly dependent on the position of the caregiver related to the patient. When the patient is lying on the bed and the caregiver is standing beside the patient near the head of the patient, the effective dose of caregiver will be the maximum value. CONCLUSIONS: Although the maximum effective dose (0.2 mSv) is smaller than the allowed value for caregivers (5 mSv for each treatment), the final results of this research indicate the importance of caregiver position in close contact with the patient.

Evaluation of boron neutron capture therapy in-phantom parameters by response matrix method.

AIM: Determination of boron neutron capture therapy in-phantom parameters by response matrix (RM) method. MATERIALS AND METHODS: In this study, various in-phantom figures-of-merit including therapeutic gain, advantage depth dose rate, advantage depth, therapeutic depth, treatment time, skin dose rate, and skull dose rate have been analyzed using the RM method. This method is based on the division of neutron/gamma spectrum and calculation of various dose components of each energy group. Summation of these dose responses is equal to the total dose of the whole spectrum. Based on this method, in-phantom parameters could be calculated by a computer program in a very short time. RESULTS: There is a good agreement between direct calculation and RM method. The maximum allowable contaminations of the thermal and fast neutrons in a neutron beam have been calculated by RM method. It was found that these values are 17.4% and 2.6%, for thermal and fast neutron, respectively. CONCLUSION: The results confirm that the RM method is a fast method to evaluate in-phantom parameters without repeating simulations due to change in neutron spectrum and treatment conditions.

Thermal and epithermal neutron flux distributions measurement in thermal column of TRR using an experimental-simulation method.

For designing an appropriate neutron beam, the determination of neutron flux at any irradiation facility is an important key factor. Due to the importance of determining the thermal and epithermal neutron fluxes in a typical thermal column of a reactor, a simple and accurate technique is introduced in this study. Absolute thermal and epithermal fluxes were measured experimentally at a certain point using the foil activation method by neutron bombardment of bare and cadmium covered Au foils. The relative neutron fluxes were also derived simply by means of Monte Carlo simulation by accurate modelling of the reactor components. Finally, by normalization of the relative distribution flux with regard to information about the absolute neutron flux, the accurate thermal and epithermal neutron distributions were derived, separately.

A novel design of beam shaping assembly to use D-T neutron generator for BNCT.

In order to use 14.1MeV neutrons produced by d-T neutron generators, two special and novel Beam Shaping Assemblies (BSA), including multi-layer and hexagonal lattice have been suggested and the effect of them has been investigated by MCNP4C Monte Carlo code. The results show that the proposed BSA can provide the qualified epithermal neutron beam for BNCT. The final epithermal neutron flux is about 6e9 n/cm2.s. The final proposed BSA has some different advantages: 1) it consists of usual and well-known materials (Pb, Al, Fluental and Cd); 2) it has a simple geometry; 3) it does not need any additional gamma filter; 4) it can provide high flux of epithermal neutrons. As this type of neutron source is under development in the world, it seems that they can be used clinically in a hospital considering the proposed BSA.

Measurement of in-phantom neutron flux and gamma dose in Tehran research reactor boron neutron capture therapy beam line.

AIM: Determination of in-phantom quality factors of Tehran research reactor (TRR) boron neutron capture therapy (BNCT) beam. MATERIALS AND METHODS: The doses from thermal neutron reactions with 14N and 10B are calculated by kinetic energy released per unit mass approach, after measuring thermal neutron flux using neutron activation technique. Gamma dose is measured using TLD-700 dosimeter. RESULTS: Different dose components have been measured in a head phantom which has been designed and constructed for BNCT purpose in TRR. Different in-phantom beam quality factors have also been determined. CONCLUSIONS: This study demonstrates that the TRR BNCT beam line has potential for treatment of superficial tumors.

Evaluation of the effective dose during BNCT at TRR thermal column epithermal facility.

An epithermal neutron beam has been designed for Boron neutron Capture Therapy (BNCT) at the thermal column of Tehran Research Reactor (TRR) recently. In this paper the whole body effective dose, as well as the equivalent doses of several organs have been calculated in this facility using MCNP4C Monte Carlo code. The effective dose has been calculated by using the absorbed doses determined for each individual organ, taking into account the radiation and tissue weighting factors. The ICRP 110 whole body male phantom has been used as a patient model. It was found that the effective dose during BNCT of a brain tumor is equal to 0.90Sv. This effective dose may induce a 4% secondary cancer risk.

Capability of NIPAM polymer gel in recording dose from the interaction of (10)B and thermal neutron in BNCT.

The capability of N-isopropylacrylamide (NIPAM) polymer gel to record the dose resulting from boron neutron capture reaction in BNCT was determined. In this regard, three compositions of the gel with different concentrations of (10)B were prepared and exposed to gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared with the gels without (10)B. It was also found that the neutron sensitivity of the gel increased by the increase of concentration of (10)B. It can be concluded that NIPAM gel might be suitable for the measurement of the absorbed dose enhancement due to (10)B and thermal neutron reaction in BNCT.

Role of gel dosimeters in boron neutron capture therapy.

Gel dosimeters have acquired a unique status in radiotherapy, especially with the advent of the new techniques in which there is a need for three-dimensional dose measurement with high spatial resolution. One of the techniques in which the use of gel dosimeters has drawn the attention of the researchers is the boron neutron capture therapy. Exploring the history of gel dosimeters, this paper sets out to study their role in the boron neutron capture therapy dosimetric process.

Design and construction of a thermal neutron beam for BNCT at Tehran Research Reactor.

An irradiation facility has been designed and constructed at Tehran Research Reactor (TRR) for the treatment of shallow tumors using Boron Neutron Capture Therapy (BNCT). TRR has a thermal column which is about 3m in length with a wide square cross section of 1.2×1.2m(2). This facility is filled with removable graphite blocks. The aim of this work is to perform the necessary modifications in the thermal column structure to meet thermal BNCT beam criteria recommended by International Atomic Energy Agency. The main modifications consist of rearranging graphite blocks and reducing the gamma dose rate at the beam exit. Activation foils and TLD700 dosimeter have been used to measure in-air characteristics of the neutron beam. According to the measurements, a thermal flux is 5.6×10(8) (ncm(-2)s(-1)), a cadmium ratio is 186 for gold foils and a gamma dose rate is 0.57Gy h(-1).

A feasibility study of the Tehran research reactor as a neutron source for BNCT.

Investigation on the use of the Tehran Research Reactor (TRR) as a neutron source for Boron Neutron Capture Therapy (BNCT) has been performed by calculating and measuring energy spectrum and the spatial distribution of neutrons in all external irradiation facilities, including six beam tubes, thermal column, and the medical room. Activation methods with multiple foils and a copper wire have been used for the mentioned measurements. The results show that (1) the small diameter and long length beam tubes cannot provide sufficient neutron flux for BNCT; (2) in order to use the medical room, the TRR core should be placed in the open pool position, in this situation the distance between the core and patient position is about 400 cm, so neutron flux cannot be sufficient for BNCT; and (3) the best facility which can be adapted for BNCT application is the thermal column, if all graphite blocks can be removed. The epithermal and fast neutron flux at the beginning of this empty column are 4.12×10(9) and 1.21×10(9) n/cm(2)/s, respectively, which can provide an appropriate neutron beam for BNCT by designing and constructing a proper Beam Shaping Assembly (BSA) structure.