Efficacy of flattening filter-free beams with the acuros XB algorithm in thoracic spine stereotactic body radiation therapy.

This study aimed to determine the dosimetric value of flattening filter-free (FFF) beams compared to flattening filter (FF) beams using different algorithms in the treatment planning of thoracic spine stereotactic body radiation therapy (SBRT). A total of 120 plans were created for 15 patients using the Anisotropic Analytical Algorithm (AAA) and the Acuros External Beam (AXB) algorithm with FF and FFF beams at 6 MV and 10 MV energies. Various dosimetric parameters were evaluated, including target coverage, dose spillage, and organs-at-risk sparing of the spinal cord and esophagus. Treatment delivery parameters, such as the monitor units (MUs), modulation factors (MFs), beam-on time (BOT), and dose calculation time (DCT), were also collected. Significant differences were observed in the dosimetric parameters when AXB was used for all energies (P < 0.05). 6 XFFF energy was the best option for target coverage, dose spillage, and organs-at-risk sparing. In contrast, dosimetric parameters had no significant difference when using the AAA. The AAA and AXB calculations showed that the 6 XFFF beam had the shortest DCT. The treatment delivery parameters indicated that 10 XFF beam required the fewest MUs and MFs. In addition, the 10 XFFF beam demonstrated the shortest BOT. For effective treatment of the thoracic spine using SBRT, it is recommended to use the 10 XFFF beam because of the short BOT. Moreover, the AXB algorithm should be used because of its accurate dose calculation in regions with tissue heterogeneity.

Assessment of diagnostic reference levels for paediatric cardiac computed tomography in accordance with European guidelines.

Recently, paediatric cardiac computed tomography (CCT) has caused concerns that diagnostic image quality and dose reduction may require further improvement. Consequently, this study aimed to establish institutional (local) diagnostic reference levels (LDRLs) for CCT for paediatric patients, and assess the impact of tube voltage on proposed DRLs in terms of the volume computed tomography index (CTDIvol) and dose length product (DLP). In addition, effective doses (EDs) of exposure were estimated. A population of 453 infants, whose mass and age were less than 12 kg and 2 years, respectively, were considered from January 2018 to August 2021. Based on previous studies, this number of patients was considered to be sufficient for establishing LDRLs. A group of 245 patients underwent CCT examinations at 70 kVp tube voltage with an average scan range of 23.4 cm. Another set of 208 patients underwent CCT examinations at 100 kVp tube voltage with an average scan range of 15.8 cm. The observed CTDIvol and DLP values were 2.8 mGy and 54.8 mGy.cm, respectively. The mean effective dose (ED) was 1.2 mSv. It is concluded that provisional establishment and use of DRLs for cardiac computed tomography in children are crucial, and further research is needed to develop regional and international DRLs.

Controlled release of silica-coated insulin-loaded chitosan nanoparticles as a promising oral administration system.

BACKGROUND: Oral insulin administration has recently become one of the most exciting research subjects. Different approaches have been carried out to get an effective oral insulin delivery system using nanotechnology. The development of a delivery system that overcomes the difficulties of oral insulin administration, achieving high stability and minimal side effects, is still an urgent need. Therefore, this study is considered one of the efforts to design a new prospective drug delivery nano-composite (silica-coated chitosan-dextran sulfate nanoparticles). METHODS: Chitosan-dextran sulfate nanoparticles (CS-DS NPs) were prepared via a complex coacervation method and then coated with silica. Uncoated and silica-coated CS-DS NPs were physically characterized via different techniques. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis, and atomic force microscopy (AFM) have been used to investigate the chemical elements, size, morphology, and surface properties of the prepared formulations. Differential scanning calorimetry (DSC) to assess the thermal properties of formed nano-formulations. Fourier transform infrared (FT-IR) spectroscopy investigated the silica coat and chitosan interaction. The encapsulation efficiency was evaluated using high-performance liquid chromatography (HPLC) analysis. The insulin release profile of nano-formulations was performed with and without silica coat at two different pHs (5.5,7), nearly simulating the environment of the gastrointestinal tract (GIT). RESULTS: The silica-coated CS-DS NPs revealed interesting physicochemical properties exemplified by suitable core particle size obtained by TEM images (145.31 ± 33.15 nm), hydrodynamic diameter (210 ± 21 nm), high stability indicated by their zeta potential value (-32 ± 3.2 mV), and adequate surface roughness assessed by AFM. The encapsulation efficiency of insulin-loaded chitosan nanoparticles (ICN) was (66.5%) higher than that of insulin-chitosan complex nanoparticles (ICCN). The silica-coated ICN demonstrated a controlled insulin release profile at pHs (5.5 and 7) compared with uncoated ICN. CONCLUSION: The silica-coated ICN can be an efficient candidate as a desired oral delivery system, overcoming the common obstacles of peptides and proteins delivery and achieving high stability and controlled release for further applications.

An insight into synthesis and antitumor activity of citrate and gallate stabilizing gold nanospheres.

Both gallic and citrate are well-established antioxidants that show promise as new selective anti-cancer drugs. Gold nanoparticles (AuNPs) as well can be developed as flexible and nontoxic nano-carriers for anti-cancer drugs. This article evaluating the efficiency and biocompatibility of gallic acid and citrate capping gold nanoparticles to be used as anti-cancer drug. The biosafety and therapeutic efficiency of prepared nano-formulations were tested on Hela and normal BHK cell line. Gold nanospheres coated with citrate and gallate were synthesized via wet chemical reduction method. The prepared nano-formulations, citrate and gallate coated gold nanospheres (Cit-AuNPs and Ga-AuNPs), were characterized with respect to their morphology, FTIR spectra, and physical properties. In addition, to assess their cytotoxicity, cell cycle arrest and flow cytometry to measure biological response were performed. Cit-Au NPs and Ga-Au NPs were shown to significantly reduce the viability of Hela cancer cells. Both G0/G cell cycle arrest and comet assay results showed that genotoxic effect was induced in Hela cells by Cit-Au NPs and Ga-Au NPs. The results of this study showed that Cit-Au NPs and Ga-AuNPs inhibit the growth of metastatic cervical cancer cells, which could have therapeutic implications.

Dosimetric evaluation study of IMRT and VMAT techniques for prostate cancer based on different multileaf collimator designs.

The hypofractionated radiotherapy modality was established to reduce treatment durations and enhance therapeutic efficiency, as compared to conventional fractionation treatment. However, this modality is challenging because of rigid dosimetric constraints. This study aimed to assess the impact of multi-leaf collimator (MLC) widths (10 mm and 5 mm) on plan quality during the treatment of prostate cancer. Additionally, this study aimed to investigate the impact of the MLC mode of energy on the Agility flattening filter (FF), MLC Agility-free flattening filter (FFF), and MLCi2 for patients receiving hypofractionated radiotherapy. Two radiotherapy techniques; Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Radiotherapy (VMAT), were used in this research. In the present study, computed tomography simulations of ten patients (six plans per patient) with localized prostate adenocarcinoma were analyzed. Various dosimetric parameters were assessed, including monitor units, treatment delivery times, conformity, and homogeneity indices. To evaluate the plan quality, dose-volume histograms (DVHs) were estimated for each technique. The results demonstrated that the determined dosimetric parameters of planning target volume (PTV)p (such as D mean, conformity, and homogeneity index) showed greater improvement with MLC Agility FF and MLC Agility FFF than with MLCi2. Additionally, the treatment delivery time was reduced in the MLC Agility FF (by 31%) and MLC Agility FFF (by 10.8%) groups compared to the MLCi2 group. It is concluded that for both the VMAT and IMRT techniques, the smaller width (5 mm) MLCs revealed better planning target volume coverage, improved the dosimetric parameters for PTV, reduced the treatment time, and met the constraints for OARs. It is therefore recommended to use 5 mm MLCs for hypofractionated prostate cancer treatment due to better target coverage and better protection of OARs.

A novel TiO2-x/TiN@ACB composite for synchronous photocatalytic Cr(VI) reduction and water photothermal evaporation under visible/infrared light illumination.

Relatively large band-gap, fast charge carriers recombination, and mono-functionality of photocatalytic materials are still representing stumbling hurdles against their optimal usage for water cleaning. Herein, a novel black titanium oxide/plasmonic titanium nitride@activated coconut biochar (TiO2-x/TiN@ACB) composite was designed to have both photocatalytic and photothermal functions. Intermediate states of black TiO2-x, plasmonic effect of TiN, and high electrons (e-) capacity of biochar enhanced band-gap narrowing, light absorbance extension, and charge carriers separation respectively. Black TiO2-x and plasmonic TiN sensitization via visible/infrared (Vis/IR) portion of photonic spectrum in addition to the confirmed close contact of composite constituents explained the demonstrated major role of e- in photocatalytic mechanism through efficient excitation and facile transfer. Thanks to black photocatalytic semiconductor and carbonic materials for their ultimate photons harnessing and efficient photothermal conversion where the composite exhibited a remarkable photothermal water evaporation upon Vis/IR illumination as well. TiO2-x/TiN@ACB composite revealed 92.8 and 89.7% photocatalytic reduction of hexavalent chromium (Cr(VI)) and water evaporation efficiencies up to 92.9 and 51.1% upon IR and Vis light illumination respectively. This study proposes a new approach for efficient water cleaning by coupling of oxygen deficient and plasmonic semiconductors supported on naturally derived carbonic material as a broad spectrum harvester and bi-functional photocatalytic and photothermal material.

Dose-enhancement of MCF 7 cell line radiotherapy using silica-iron oxide nanocomposite.

Cancer radiotherapy is one of the most effective regimens of cancer treatments, but cancer cell radioresistance remains a concern. Radiosensitizers can selectively improve the efficacy of radiotherapy and reduce inherent damage. The purpose of this work is to evaluate the effect of silica-coated iron oxide magnetic nanoparticles (SIONPs) as a radiosensitizer and compare their therapeutic effect with that of Iron oxide magnetic nanoparticles (IONPs). IONPs and SIONPs were characterized using several physical techniques such as a transmission electron microscope (TEM) and Vibrating sample magnetometer (VSM). MTT and DNA double-strand breaks (Comet) assays have been used to detect the cytotoxicity, cell viability, and DNA damage of MCF-7 cells, which were treated with different concentrations of prepared nanoparticles and exposed to an X-ray beam. In this study, an efficient radiosensitizer, SIONPs, was successfully prepared and characterized. With 0.5 Gy dose, dose enhancement factor (DEF) values of cells treated with 5 and 10 µg/ml of IONPs were 1 and 1.09, respectively, while those treated with SIONPs at these concentrations had DEF of 1.21 and 1.32, respectively. Results demonstrated that SIONPs provide a potential for improving the radiosensitivity of breast cancer.

Novel lipid-coated mesoporous silica nanoparticles loaded with thymoquinone formulation to increase its bioavailability in the brain and organs of Wistar rats.

AIMS: The Blood-Brain Barrier (BBB) is a filter for most medications and blocks their passage into the brain. More effective drug delivery strategies are urgently needed to transport medications into the brain. This study investigated the biodistribution of thymoquinone (TQ) and the effect on enzymatic and non-enzymatic oxidative stress indicators in different brain regions, either in free form or incorporated into nanocarriers as mesoporous silica nanoparticles (MSNs). Lipid bilayer-coated MSNs. MATERIALS AND METHODS: MSNs and LB-MSNs were synthesized and characterized using a transmission electron microscope and dynamic light scattering to determine the particle size and zeta potential. TQ encapsulation efficiency and TQ's release profile from LB-MSNs were also examined. The impact of loading LB-MSNs with TQ-on-TQ delivery to different brain areas was examined using chromatographic measurement. Furthermore, nitric oxide, malondialdehyde (MDA), reduced glutathione, and catalase were evaluated as oxidant and antioxidant stress biomarkers. KEY FINDINGS: The LB-MSNs formulation successfully transported TQ to several areas of the brain, liver, and kidney, revealing a considerable increase in TQ delivery in the thalamus (81.74%) compared with that in the free TQ group and a considerable reduction in the cortex (-44%). The LB-MSNs formulation had no significant effect on TQ delivery in the cerebellum, striatum, liver, and kidney. SIGNIFICANCE: TQ was redistributed in different brain areas after being encapsulated in LB-MSNs, indicating that LB-MSNs have the potential to be developed as a drug delivery system for selective clinical application of specific brain regions. CONCLUSIONS: LB-MSNs are capable nanoplatforms that can be used to target medications precisely to specific brain regions.

Targeting SARS-CoV-2 endoribonuclease: a structure-based virtual screening supported by in vitro analysis.

Researchers are focused on discovering compounds that can interfere with the COVID-19 life cycle. One of the important non-structural proteins is endoribonuclease since it is responsible for processing viral RNA to evade detection of the host defense system. This work investigates a hierarchical structure-based virtual screening approach targeting NSP15. Different filtering approaches to predict the interactions of the compounds have been included in this study. Using a deep learning technique, we screened 823,821 compounds from five different databases (ZINC15, NCI, Drug Bank, Maybridge, and NCI Diversity set III). Subsequently, two docking protocols (extra precision and induced fit) were used to assess the binding affinity of the compounds, followed by molecular dynamic simulation supported by the MM-GBSA free binding energy. Interestingly, one compound (ZINC000104379474) from the ZINC15 database has been found to have a good binding affinity of - 7.68 kcal/Mol. The VERO-E6 cell line was used to investigate its therapeutic effect in vitro. Half-maximal cytotoxic concentration and Inhibitory concentration 50 were determined to be 0.9 mg/ml and 0.01 mg/ml, respectively; therefore, the selectivity index is 90. In conclusion, ZINC000104379474 was shown to be a good hit for targeting the virus that needs further investigations in vivo to be a drug candidate.

Surface modifications affect iron oxide nanoparticles' biodistribution after multiple-dose administration in rats.

Iron oxide nanoparticles (IONPs) possess many utilizable physical and chemical properties and have an acceptable level of biocompatibility. Therefore, they are extensively used in different medical applications. Hence, the challenge is to modify the surfaces of prepared iron oxide nanoformulations with a biocompatible coat to enhance their biosafety. In this study, different formulations of IONPs with different capping agents (citrate [Cit-IONPs], curcumin [Cur-IONPs], and chitosan [CS-IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit-IONPs, Cur-IONPs, CS-IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4 mg/kg of body weight/day. The results were compared with a control group injected orally with saline. The iron content in the kidneys, liver, and spleen was measured by atomic absorption spectroscopy. Histopathological alterations were also examined. The biodistribution results demonstrate that iron accumulated mainly in the liver tissue, whereas the lowest liver accumulation was observed after the administration of Cit-IONPs or CS-IONPs, respectively. In contrast, the administration of CS-IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO4 )-treated group showed the highest kidney iron accumulation as compared with the other groups. The histopathological examination revealed that signs of toxicity were predominant for groups treated with Cit-IONPs or commercial FeSO4 . However, Cur-IONPs and CS-IONPs showed mild toxicity when administered at the same doses. The results obtained in the present study will provide insights into the expected in vivo effects after administration of each nanoformulation.

Magnetic nanoparticles-loaded liposomes as a novel treatment agent for iron deficiency anemia: In vivo study.

Iron deficiency anemia (IDA) is a major worldwide public health problem. This is due to its prevalence among infants, children, adolescents, pregnant and reproductive age women. Ferrous sulfate (FeSO4) is the first line therapy for iron IDA. Unfortunately, it is reported that FeSO4 suffers from low absorption rate in the body and itself exhibits severe side effects. Herein, iron oxide magnetic nanoparticles-loaded liposomes (LMNPs) are prepared, characterized and evaluated as a treatment regimen for IDA in Wistar rats (as an animal model). Iron oxide magnetic nanoparticles (MNPs) are prepared and loaded into liposomes using the thin film hydration method. The size of the prepared formulations is in the range 10-100 nm, thus it can avoid the reticular endothelial system (RES), and increased their blood circulation time. For in vivo assessment, thirty-five Wistar rats are divided into 5 groups (n = 7): negative control group, positive control group, and three groups treated with different iron formulations (FeSO4, MNPs and LMNPs). Anemia is induced in the anemic groups by the bleeding method and then treatment started with different iron compounds administrated orally for 13 days. Hematological parameters are followed up during the treatment period. Results indicate that, in the LMNPs group, the hematological parameters turn to normal values and the histopathological structures of the liver, spleen and kidney remain normal. This proves that liposome increases the bioavailability of MNPs. In conclusion, LMNPs demonstrate superiority as a therapeutic regimen for the treatment of IDA among the tested iron formulations.

Silica-coated iron oxide nanoparticles as a novel nano-radiosensitizer for electron therapy.

AIMS: Conventional radiotherapy is mainly restricted by the low radiation absorption efficiency of tumors tissues and the hypoxic tumor cells radio-resistance. In this paper, novel nano-radiosensitizers, magnetic nanoparticles core coated with silica, were successfully prepared to overcome these limitations. MAIN METHODS: The prepared nanoparticles have been characterized by transmission electron microscope (TEM), Dynamic light scattering (DLS), atomic force microscope (AFM) and vibration sample magnetometer (VSM). MTT cytotoxicity and DNA double-strand breaks (Comet) assays have been used to assess the radio-enhancing effect of iron oxide magnetic nanoparticles (IO-MNPs) and silica-coated iron oxide magnetic nanoparticles (SIO-MNPs) against MCF7 breast cancer cells. MCF7 cells were treated with different concentrations of the prepared nanoformulations and exposed to an electron beam at doses 0, 0.5, 1, 2, 4 Gy. KEY FINDINGS: DLS measurements revealed that the main hydrodynamic diameter of the prepared IO-MNPs and SIO-MNPs was 18.17 ±â€¯4.5 nm and 164.18 ±â€¯16.1 nm, respectively, which was confirmed by TEM micrographs. MTT and comet assays results showed that the radiosensitizing effect of the prepared nanoformulations was dose and concentration dependent. Interestingly, the dose enhancement factor (DEF) for SIO-MNPs was, on average, 1.3-fold greater than that of IO-MNPs. SIGNIFICANCE: Coating of IO-MNPs with silica led to enhance their electron radiosensitization and consequently their therapeutic efficacy. Therefore, SIO-MNPs represent a promising engineered nano-formulation for enhancing breast cancer radiosensitivity.

Targeting of Thymoquinone-loaded mesoporous silica nanoparticles to different brain areas: In vivo study.

AIMS: Drug delivery to the brain is hindered by the blood-brain-barrier (BBB) that filters out most of drugs after systemic administration. Therefore, there is an urgent need to develop more efficient drug delivery systems to deliver pharmaceuticals to brain. In this work, the distribution and the effect of Thymoquinone (TQ) on different oxidative stress biomarkers in different brain areas, either in the free form or encapsulated in mesoposrous silica nanocarriers (MSNs) were systematically studied. MATERIALS AND METHODS: MSNs and Thymoquinone-loaded mesoporous silica nanoparticles (MSN-TQ) were prepared and characterized using TEM, DLS, and zeta potential. The encapsulation efficiency and release profile of MSN-TQ were investigated as well. The chromatographic quantification of TQ was carried out to evaluate the effect of TQ loading in MSNs on the TQ distribution throughout different brain regions. Additionally, some oxidative stress biomarkers were evaluated like: glutathione reduced (GSH), glutathione-s-transferase (GST), nitric acid (NO) and malondialdehyde (MDA). KEY FINDINGS: Results showed that the encapsulation of TQ in MSNs enhanced its delivery to some brain areas (cortex, thalamus, hypothalamus and midbrain), on the other hand it reduced its delivery to the cerebellum while its delivery to medulla and striatum was not changed compared to free TQ. Neither free TQ nor MSN-TQ were able to reach the hippocampus. SIGNIFICANCE: It was found that the encapsulation of TQ in MSNs resulted in its redistribution in different brain areas, thus, MSNs could be potentially utilized as a drug delivery system for selectively targeting the drug to certain brain areas.

Multifunctional magnetic-gold nanoparticles for efficient combined targeted drug delivery and interstitial photothermal therapy.

Abundant efforts have recently been made to design potent theranostic nanoparticles, which combine diagnostic and therapeutic agents, for the effective treatment of cancer. In this study, we developed multifunctional magnetic gold nanoparticles (MGNPs) that are able to (i) selectively deliver the drug to the tumor site in a controlled-release manner, either passively or by using magnetic targeting; (ii) induce photothermal therapy by producing heat by near-infrared (NIR) laser absorption; and (iii) serve as contrast agents for magnetic resonance imaging (MRI) (imaging-guided therapy). The prepared MGNPs were characterized by different physical techniques. They were then coated and conjugated with polyethylene glycol (PEG) and doxorubicin (DOX) to form MGNP-DOX conjugates. The high efficacy of MGNP-DOX for combined chemo-photothermal therapy was observed both in vitro and in vivo. The effectiveness of MGNP-DOX as theranostic nanoparticles was confirmed by histopathological examination and immunohistochemical studies. Moreover, MGNP-DOX showed good potential as MRI contrast agents for guided chemo-photothermal synergistic therapy.

Enhanced therapeutic benefit of quercetin-loaded phytosome nanoparticles in ovariectomized rats.

Quercetin, a dietary flavonol phytoestrogen, has many health benefits but it is poorly absorbed when administered orally. To improve its bioavailability, we prepared quercetin-loaded phytosome nanoparticles (QP) using the thin film hydration method. The prepared nano-formulations were characterized using different techniques. Transmission electron microscopy revealed the homogeneously spherical, well and uniformly dispersed, nano-sized nature of QP. Dynamic light scattering measurements of QP (70 ± 7.44 nm) also confirmed this. Stability of the formed nanoparticles was established via zeta potential determination. The prepared QP exhibited very high encapsulation efficiency (98.4%). The estrogenic activity of QP, concerning inflammation, oxidative stress, bone, lipid profile, blood glucose level and weight gain, was investigated in ovariectomized rat model using 10 and 50 mg/kg/day oral doses for 4 weeks. Treatment with QP showed significant increase in serum calcium, inorganic phosphorus and glutathione content. Whereas, it significantly decreased serum alkaline phosphatase, acid phosphatase, malondialdehyde level, tumor necrosis factor-alpha and glucose level and improved lipid profile. Consequently, the results obtained confirm the superiority of QP over free quercetin at the same doses as a promising hormone replacement therapy.