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Super Paramagnetic Iron Oxide Nanoparticles have attracted much attention in drug delivery systems because of their considerable surface-to-volume ratio and content as well. In this regard, in this study, four different formulations of magnetic nanoparticles were synthesized via various polymeric coating layer (beta-cyclodextrin, Chitosan, Gum Arabic, and Alginate) in order to find an appropriate polymer in terms of higher drug loading efficiency and capacity. Molecular dynamics simulation and Quantum mechanics were manipulated to examine the interaction mechanism between the polysaccharide polymers and Doxorubicin. Based on the calculated results, As the best candidate, bCD was chosen for DOX loading. DOX, a hydrophilic drug, was loaded into each of the four formulations. The optimum formulation, Fe3O4-ßCD, possessed loading efficiency and capacity, with 97% and 13%, respectively. The selected nanocarrier was fully characterized by Fourier Transform Infrared, VSM, TGA, XRD, SEM, UV-Vis, DLS, and TEM. TEM result exhibited the prepared Fe3O4-ßCD-DOX nanoparticles had a spherical shape (core and shell) and the size of around 15 nm. In vitro release investigation was conducted using HPLC analysis in the phosphate-buffered saline in acidic (pH=5.4) and neutral (pH=7.4) medium. The obtained results demonstrated that a sustain release performance for more than 72 h with the amount of 50% DOX release in pH=5.4. Cytotoxicity assay showed the toxicity of bare Fe3O4 and Fe3O4-ßCDNPsagainst MDA-MB468 cancerous cell and MCF10A normal cell was negligible and DOX-loaded NPs (Fe3O4-ßCD-DOX) illustrated a higher toxicity in MDA-MB468 cancerous cells than MCF 10A normal cells. The results showed that Fe3O4-ßCD-DOXNPs could improve the therapeutic efficacy and also reduce the adversarial effects; accordingly, the prepared system could be served as a promising drug delivery system in cancer treatment. [ABSTRACT FROM AUTHOR]

The combination of imaging contrast media and treatment strategies in one nanosystem has received great attention for cancer detection and treatment. This study aimed to develop Au@MnO/PEG/5FU (AMP/5FU) nanoparticles (NPs) for dual-modal CT/MRI and 5-Fluorouracil (5FU) anticancer drug delivery. The NPs showed a high 5FU loading capacity (90%), pH-responsive release profile, considerable X-ray attenuation, and MRI r1 relaxivity of 4.36 mM−1s−1. They had a significant toxic impact against A549 cancer cells that was greater than that of free 5FU. AMP/5FU NPs can be considered as a high potential multifunctional nanosystem for dual-modal CT/MRI and pH-responsive 5FU delivery. [ABSTRACT FROM AUTHOR]

This study introduces a simple method for preparing a new generation of MnO2 nanomaterials (MNMs) using tannic acid as a template. Two shapes of MnO2 NMs, flower-like M1-MnO2 and near-spherical M2-MnO2, were prepared and compared as dual-active nanozymes and contrast agents in magnetic resonance imaging (MRI). Various parameters, including the crystallinity, morphology, magnetic saturation (Ms), surface functionality, surface area, and porosity of the MNMs were investigated. Flower-like M1-MnO2 NMs were biocompatible and exhibited pH-sensitive oxidase and peroxidase mimetic activity, more potent than near-spherical M2-MnO2. Furthermore, the signal intensity and r1 relaxivity strongly depended on the crystallinity, morphology, pore size, and specific surface area of the synthesized MNMs. Our findings suggest that flower-like M1-MnO2 NM with acceptable dual-enzyme mimetic (oxidase-like and peroxidase-like) and T1 MRI contrast activities could be employed as a promising theranostic system for future purposes. [ABSTRACT FROM AUTHOR]

Objective: A novel efficient pH-sensitive targeted magnetic resonance imaging (MRI) contrast agent and innovative radio-sensitizing system were synthesized based on MnO2 NPs coated with biocompatible poly-dimethyl-amino-ethyl methacrylate-Co-itaconic acid, (DMAEMA-Co-IA) and targeted with methotrexate (MTX). Materials and methods: The as-established NPs were fully characterized and evaluated for MRI signal enhancement, relaxivity, in vitro cell targeting, cell toxicity, blood compatibility, and radiotherapy (RT) efficacy. Results: The targeted NPs MnO2@Poly(DMAEMA-Co-IA) and MTX-loaded NPs inhibited MCF-7 cell viability more effectively than free MTX after 24 and 48 h, respectively, with no noticeable toxicity. Additionally, the insignificant hemolytic activity demonstrated their proper hemo-compatibility. T1-weighted magnetic resonance imaging was used to distinguish the differential uptake of the produced MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in malignant cells compared to normal ones in the presence of high and low MTX receptor cells (MCF-7 and MCF-10A, respectively). In MRI, the produced theranostic NPs displayed pH-responsive contrast enhancement. As shown by in vitro assays, treatment of cells with MnO2@Poly(DMAEMA-Co-IA)-MTX NPs prior to radiotherapy in hypoxic conditions significantly enhanced therapeutic efficacy. Conclusion: We draw the conclusion that using MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in MR imaging and combination radiotherapy may be a successful method for imaging and radiation therapy of hypoxia cells. [ABSTRACT FROM AUTHOR]

A novel targeted tumor contrast agent in magnetic resonance imaging (MRI) was synthesized based on Fe3O4@Au nanoparticle coated with polyethylene glycol (PEG) and decorated with trastuzumab (TZ). The prepared system was fully characterized, and relaxivity, cytotoxicity, colloidal stability, blood compatibility, in vitro cell targeting ability, cytotoxicity, and in vivo MR contrast enhancement were evaluated. The developed system with a size of about 30 nm exhibited excellent stability, blood compatibility, proper relaxivity, negligible in vitro cytotoxicity, and suitable in vivo negative contrast enhancement. Appropriate negative signal enhancement in MRI confirmed the efficiency of the system to be suggested as an encouraging candidate for accurate cancer diagnosis. [ABSTRACT FROM AUTHOR]

Although the chemotherapeutic drug, doxorubicin, is commonly used to treat various malignant tumors, its clinical use is restricted because of its toxicity especially cardiotoxicity. The use of curcumin may alleviate some of the doxorubicin‐induced cardiotoxic effects. Especially, using the nano‐formulation of curcumin can overcome the poor bioavailability of curcumin and enhance its physicochemical properties regarding its efficacy. In this study, we systematically reviewed the potential cardioprotective effects of nano‐curcumin against the doxorubicin‐induced cardiotoxicity. A systematic search was accomplished based on Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for the identification of all relevant articles on "the role of nano‐curcumin on doxorubicin‐induced cardiotoxicity" in the electronic databases of Scopus, PubMed, and Web of Science up to July 2021. One hundred and sixty‐nine articles were screened following a predefined set of inclusion and exclusion criteria. Ten eligible scientific papers were finally included in the present systematic review. The administration of doxorubicin reduced the body and heart weights of mice/rats compared to the control groups. In contrast, the combined treatment of doxorubicin and nano‐curcumin increased the body and heart weights of animals compared with the doxorubicin‐treated groups alone. Furthermore, doxorubicin could significantly induce the biochemical and histological changes in the cardiac tissue; however, coadministration of nano‐curcumin formulation demonstrated a pattern opposite to the doxorubicin‐induced changes. The coadministration of nano‐curcumin alleviates the doxorubicin‐induced cardiotoxicity through various mechanisms including antioxidant, anti‐inflammatory, and antiapoptotic effects. Also, the cardioprotective effect of nano‐curcumin formulation against doxorubicin‐induced cardiotoxicity was higher than free curcumin. [ABSTRACT FROM AUTHOR]

Background: Nowadays, there has been a growing demand for low-dose computed tomography (LDCT) protocols. CT has a critical role in the management of the diagnosis chain of pulmonary disease, especially in lung cancer screening. There have been introduced several dose reduction methods, however, most of them are time-consuming, intricate, and vendor-based strategies that are hardly used in clinics routinely. This study aims to evaluate the image quality and pulmonary nodule detectability of LDCT protocols that are feasible and easy implemented. Image quality was analyzed in a general quality control phantom (Gammex) and then in a manmade lung phantom with nodules-equivalent objects. Methods: This study was designed in a two steps, in the first step, a feasible low-dose lung CT protocol was selected with quality assessment of accreditation phantom image. In the second step, the selected low-dose protocol with an appropriate image quality was performed on a manmade lung phantom in which there were objects equivalent to the pulmonary nodule. Finally, image quality parameters of the phantom at the appropriate scan protocol were compared with the standard protocol. Results: A reduction of about 17% of kVp and 46% in tube current leads to dose reduction by about 70%. The contrast-to-noise ratio in the low-dose protocol remained almost unchanged. The signal-to-noise ratio in the low-dose protocol decreased by approximately 32%, and the noise level has increased by about 1.5 times. However, this reduction method hardly affected the detectability of nodules in man-made pulmonary phantom. Conclusions: Here, we demonstrated that the LDCT scan has an insignificant effect on the perception of lung nodules. In this study, patient dose in lung CT was reduced by modifying of kVp and mAs about approximately 70%. Hence, to step in toward low-dose strategies in medical imaging clinics, using easy-implemented and feasible low-dose strategies may be helpful. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to optimise computed tomography (CT) simulation scan parameters to increase the accuracy for gross tumour volume identification in brain radiotherapy. For this purpose, high-contrast scan protocols were assessed. Materials and methods: A CT accreditation phantom (ACR Gammex 464) was used to optimise brain CT scan parameters on a Toshiba Alexion 16-row multislice CT scanner. Dose, tube voltage, tube current–time and CT dose index (CTDI) were varied to create five image quality enhancement (IQE) protocols. They were assessed in terms of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and noise level and compared with a standard clinical protocol. Finally, the ability of the selected protocols to identify low-contrast objects was examined based on a subjective method. Results: Among the five IQE protocols, the one with the highest tube current–time product (250 mA) and lowest tube voltage (100 kVp) showed higher CNR, while another with a tube current–time product of 150 mA and a tube voltage of 135 kVp had improved SNR and lower noise level compared to the standard protocol. In contouring low-contrast objects, the protocol with the highest milliampere and lowest peak kilovoltage exhibited the lowest error rate (1%) compared to the standard protocol (25%). Findings: CT image quality should be optimised using the high-dose parameters created in this study to provide better soft tissue contrast. This could lead to an accurate identification of gross tumour volume recognition in the planning of radiotherapy treatment. [ABSTRACT FROM AUTHOR]

Contrast agents (CAs) play a critical role in high-resolution magnetic resonance imaging (MRI) applications to enhance the low intrinsic sensitivity of MRI. Manganese oxide nanoparticles (MnO) have gotten developing consideration as substitute spin-lattice (T1) MRI CAs as a result of the Gd-based CAs which are related with renal fibrosis as well as the inherent dark imaging characteristics of superparamagnetic iron oxide NPs. In this review, previous developments in the usage of MnO nanoparticles as MRI CAs for cancer theranostic applications such as developments in toxicological properties, distribution and tumor microenvironment (TME)-responsive biomaterials were reviewed. A literature search was accomplished to discover distributed research that elaborates the use of MnO in multimodal imaging and therapy. In the current study, the electronic search including PubMed/Medline, Embase, ProQuest, Scopus, Cochrane and Google Scholar was performed dependent on Mesh key words. CAs can significantly improve the imaging contrast among the lesions and normal tissues. In this study we generally concentrate on typical advancements of MnO nanoparticles about properties, bimodal or multimodal imaging, and therapy. Numerous researches have demonstrated MnO-based nanostructure produce considerable biocompatibility with the lack of cytotoxicity. Therefore, remarkable features improved photothermal therapy, chemotherapy and Chemodynamic therapy. [ABSTRACT FROM AUTHOR]

β-Cyclodextrine-based polyester was coated on the surface of gadolinium oxide nanoparticles (NPs) and then functionalised with folic acid to produce an efficient pH-sensitive targeted theranostic system (Gd2O3@PCD-FA) for doxorubicin delivery and magnetic resonance imaging (MRI). Gd2O3@PCD-FA was fully characterised by FTIR, vibrating sample magnetometer, TGA, XRD, SEM and TEM analyses. The dissolution profile of DOX showed a pH sensitive release. No significant toxicity was observed for the targeted NPs (Gd2O3@PCD-FA) and DOX-loaded NPs inhibiting M109 cells viability more efficiently than free DOX. Moreover, the negligible hemolytic activity of the targeted NPs showed their appropriate hemocompatibility. The preferential uptake was observed for the developed Gd2O3@PCD-FA-DOX NPs in comparison with Dotarem using T1- and T2-weighted MRI in the presence of folate receptor-positive and folate receptor-negative cancer cells (M109 and 4T1, respectively). Furthermore, in vivo studies revealed that Gd2O3@PCD-FA-DOX not only exhibited considerably relaxivity performance as a contrast agent for MRI, but also improved in vivo anti-tumour efficacy of the system. The results suggest that Gd2O3@PCD-FA-DOX improves its therapeutic efficacy in the treatment of solid tumours and also reduces the adverse effects, so it could be proposed as a promising drug delivery system for chemotherapy and molecular imaging diagnosis in MRI. [ABSTRACT FROM AUTHOR]

In Iran, a developing country in southwest Asia, an epidemiologic transition is underway from communicable to noncommunicable diseases. In Iran, cancer is the second largest group of chronic non-communicable diseases (NCDs) and the third most common cause of death following heart disease, accidents and other natural phenomena. There are some studies reporting an increasing trend in the incidence and mortality rate of a variety of cancers in Iran. Therefore, controlling and preventive interventions pertaining to cancers must be a main priority for health policy and it is recommended that the high-risk population receive earlier screening. In this review, incidence and mortality of colorectal, lung, liver, thyroid, and bladder cancers in Iran are reported. [ABSTRACT FROM AUTHOR]

Aim of the study: Our objective was to quantify the accuracy of dose calculation in the build-up region of the tangential field of the breast for a Ti- GRT treatment planning system (TPS). Material and methods: Thermoluminescent dosimeter (TLD) chips were arranged in a RANDO phantom for the dose measurement. TiGRT TPS was also used for the dose calculation. Finally, confidence limit values were obtained to quantify the accuracy of the dose calculation of the TPS at the build-up region. Results: In the open field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 17.68, 19.97, and 34.62 at a depth of 5 mm, and 24.01, 19.07, and 15.74 at a depth of 15 mm, respectively. In the wedge field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 21.64, 26.80, and 34.87 at a depth of 5 mm, and 27.92, 22.04, and 20.03 at a depth of 15 mm, respectively. Additionally, the findings showed that at a depth of 5 mm, the confidence limit values increased with increasing gantry angle while at a depth of 15 mm, the confidence limit values decreased with increasing gantry angle. Conclusions: Overall, TiGRT TPS overestimated doses compared to TLD measurements, and the confidence limit values were greater for the wedge field than for the open fields. Our findings suggest that the assessment of dose distributions in largedose gradient regions (i.e. build-up region) should not entirely rely on TPS calculations. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) have shown a great potential as a novel contrast agent in magnetic resonance imaging (MRI) due to their unique properties including versatile structures, composition, and surface chemistry. Fe-MIL-88B-NH2 (MILs) was synthesized using Fe+3 ions and 2-aminoterephthalic acids (NH2-BDC) in the presence of acetic acid and Pluronic F127 under a hydrothermal process. Three MILs in different sizes were synthesized by using variant CH3COOH/Fe+3 molar ratios and denoted as MIL-S, MIL-M, and MIL-L having average sizes of 60, 350, and 730 nm, respectively. The effect of aspect ratio and particle size of MILs was investigated on proton relaxivity and contrast enhancement in aqueous, in vitro, and in vivo MR images. MRI study indicated that by increasing the MILs size, the incremental transverse relaxivity was achieved from 13.53 to 50.80 for r2 and from 38.75 to 60.25 for r2*, while the difference between r2 and r2* was decreased obviously. The r2/r1 ratios were found to be 5.80, 42.27, and 127.00 for MIL-S, MIL-M, and MIL-L, respectively. All MILs demonstrated T2-weighted MR imaging performance. Furthermore, no susceptibility artifacts were observed on T2-weighted images of MILs. By decreasing the size of MILs, r2/r1 ratio was reduced sharply and T1 contrast was also observed for MIL-S. MIL-S was used for in vitro and in vivo study due to its capability in simultaneous T1 and T2 contrast enhancements. MTT and hemolysis assays showed no significant cytotoxicity and hemolysis for MIL-S against normal human breast cell line (MCF-10A) and red blood cells, respectively, at concentrations of Fe+3 up to 300 μg/mL (p < 0.05). T1-weighted images acquired from in vitro study interestingly showed that the signal intensity of MIL-S is more than Dotarem. The in vivo experiment revealed that the signal intensity of mice liver decreased sharply after injection resulting in increase of negative contrast enhancement. The negative contrast enhancement decreased gradually by the time under T2-weighted imaging mode confirming application of MIL-S as a T2 contrast agent in biomedical applications (up to 12 h post-injection). Although a decrease of the size resulted in bright contrast in aqueous solution for MIL-S, it did not show proper efficiency for in vivo positive contrast enhancement. The advantages, including simple preparation and accessibility, acceptable potency and selectivity, blood compatibility, and suitable cytocompatibility as well as enough circulation time, make MIL-S as a dual MRI contrast agent to differentiate between low-contrast tissues for in vivo experiments. [ABSTRACT FROM AUTHOR]

In an attempt to find new potent cytotoxic compounds, several mono- and bis-pyrazolophthalazines 4a-m and 6a-h were synthesized through an efficient, one-pot, three- and pseudo five-component synthetic approach. All derivatives were evaluated for their in vitro cytotoxic activities against four human cancer cell lines of A549, HepG2, MCF-7, and HT29. Compound 4e showed low toxicity against normal cell lines (MRC-5 and MCF 10A, IC 50 > 200 µM) and excellent cytotoxic activity against A549 cell line with IC 50 value of 1.25 ± 0.19 µM, which was 1.8 times more potent than doxorubicin (IC 50 = 2.31 ± 0.13 µM). In addition, compound 6c exhibited remarkable cytotoxic activity against A549 and MCF-7 cell lines (IC 50 = 1.35 ± 0.12 and 0.49 ± 0.01 µM, respectively), more than two-fold higher than that of doxorubicin. The binding properties of the best active mono- and bis-pyrazolophthalazine (4e and 6c) with HSA and DNA were fully evaluated by various techniques including UV–Vis absorption, circular dichroism (CD), Zeta potential and dynamic light scattering analyses indicating interaction of the compounds with the secondary structure of HSA and significant change of DNA conformation, presumably via a groove binding mechanism. Additionally, molecular docking and site-selective binding studies confirmed the fundamental interaction of compounds 4e and 6c with base pairs of DNA. Compounds 4e and 6c showed promising features to be considered as potential lead structures for further studies in cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Nowadays, there has been a growing demand for low-dose computed tomography (LDCT) protocols. CT has a critical role in the management of the diagnosis chain of pulmonary disease, especially in lung cancer screening. There have been introduced several dose reduction methods, however, most of them are time-consuming, intricate, and vendor-based strategies that are hardly used in clinics routinely. This study aims to evaluate the image quality and pulmonary nodule detectability of LDCT protocols that are feasible and easy implemented. Image quality was analyzed in a general quality control phantom (Gammex) and then in a manmade lung phantom with nodules-equivalent objects., Methods: This study was designed in a two steps, in the first step, a feasible low-dose lung CT protocol was selected with quality assessment of accreditation phantom image. In the second step, the selected low-dose protocol with an appropriate image quality was performed on a manmade lung phantom in which there were objects equivalent to the pulmonary nodule. Finally, image quality parameters of the phantom at the appropriate scan protocol were compared with the standard protocol., Results: A reduction of about 17% of kVp and 46% in tube current leads to dose reduction by about 70%. The contrast-to-noise ratio in the low-dose protocol remained almost unchanged. The signal-to-noise ratio in the low-dose protocol decreased by approximately 32%, and the noise level has increased by about 1.5 times. However, this reduction method hardly affected the detectability of nodules in man-made pulmonary phantom., Conclusions: Here, we demonstrated that the LDCT scan has an insignificant effect on the perception of lung nodules. In this study, patient dose in lung CT was reduced by modifying of kVp and mAs about approximately 70%. Hence, to step in toward low-dose strategies in medical imaging clinics, using easy-implemented and feasible low-dose strategies may be helpful., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Medical Signals & Sensors.)