Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701Gold nanoparticles as cancer theranostic agents1471601323010.22038/ nmj.2019.06.00001ENAtefeh RostamiDepartment of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranAmeneh SazgarniaDepartment of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranMedical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, IranJournal Article20190603The application of nanotechnology in medicine involves using nanomaterials to develop novel therapeutic and diagnostic modalities. Given the unique physiochemical and optical properties of gold nanoparticle (GNP) such as good biocompatibility, nontoxic nature, surface properties and comparative stability, it has been widely studied in medicine, especially as a cancer theranostic agent. <br />This review focuses on recent progresses in the field of gold nanostructures in cancer treatment and diagnosis. As far as cancer detection is concerned, several studies have indicated that GNPs can be used for X-ray, MR and optical imaging. With regard to cancer treatment, most studies have investigated the effect of GNPs in different treatment modalities like photothermal therapy, photodynamic therapy, sonodynamic therapy, drug delivery, and radiotherapy. <br />In this paper, we have focused on reviewing the role of GNPs in improving radiotherapy efficiency as radiosensitizers. For optimization of parameters influencing the radiosensitization of GNPs, several studies have been undertaken in different scientific routes. We categorize these studies into three categories; Monte Carlo simulation, cellular studies and animal studies. Finally, according to findings reported by different researchers, the physical and biological mechanism of GNPs in generating radiosensitizing effect is discussed.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701Assessment of pulmonary mucociliary transport using magnetic nanoparticles: influence of their surface potential1611661310210.22038/nmj.2019.06.00002ENKohei NishimotoDepartment of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanSatoshi NaganoGlobal Center for Medical Engineering and Informatics, Osaka University, Suita, Osaka, JapanKenya MuraseDepartment of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanGlobal Center for Medical Engineering and Informatics, Osaka University, Suita, Osaka, Japan0000-0003-2040-9842Journal Article20190515Objective(s): Inhaled aerocontaminants are removed from the lungs by pulmonary mucociliary transport (MCT) as an important defense mechanism. This study was undertaken to investigate the influence of the surface potential of magnetic nanoparticles (MNPs) on the MCT in murine lungs by use of magnetic particle imaging (MPI).<br />Materials and Methods: Three kinds of MNPs (carboxymethyl dextran magnetite (CM), alkali-treated dextran magnetite (AM), and trimethylammonium dextran magnetite (TM)) with almost the same hydrodynamic diameters (50-55 nm) but different surface (zeta) potentials (−24 mV for CM, −15 mV for AM, and +2 mV for TM) were intratracheally injected to anesthetized ICR male mice at 10 weeks old using a nebulizing microsprayer containing 50 μL of MNPs. MPI images were acquired at 0.5, 6, 24, 72, and 168 hours after the injection of agents for each mouse. The retention value of the MNPs in the lungs was quantified from the average pixel value of the lungs in the MPI image. <br />Results: The retention value of TM in the lungs was significantly greater than that of AM at 6 and 168 hours after the injection of agents, and was significantly greater than that of CM at 72 and 168 hours after injection. The retention value of AM was significantly greater than that of CM at 168 hours after injection.<br />Conclusion: The surface potential of MNPs affects the clearance of MNPs from the lungs due to MCT, suggesting that the retention of MNPs in the lungs can be controlled by manipulating the surface potential of MNPs. MPI will be useful for the visual and quantitative assessment of MCT, because MPI allows for repeated and long-term studies with a single injection of MNPs and with no radiation exposure.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701Investigation of osteoblast-like cells cultured on nano-hydroxyapatite/chitosan based composite scaffold in the treatment of bone defects and limited mobility1671751312410.22038/nmj.2019.06.00003ENAsgar EmamgholiDepartment of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0002-0545-7654Mohsen RahimiDepartment of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0002-2537-651xSeyyed Javad Seyyed TabaeiDepartment of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranTeymoor GhorbaniNeuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranSeyed Ali ZiaiDepartment of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranPeiman Brouki MilanDepartment of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, IranMahdi KhodadoustNeuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran0000-0001-9826-7915Nafiseh KeshavarzianDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranJournal Article20190519Objective(s): Design and construction of biocompatible and biodegradable scaffolds are among the main goals of tissue engineering. Recently, use of nano-hydroxyapatite as a bioactive bioceramic agent with high similarity to the mineral phase of the human bone tissue, in combination with biodegradable polymers and implant coatings has attracted the attention of researchers in the field of biomaterial sciences. The present study aimed to assess the differentiation of bone marrow stromal cells (BMSCs) in osteoblast-like cells on the chitosan/polyethylene oxide (PEO)/nano-hydroxyapatite scaffold in mature rats.<br />Materials and Methods: Chitosan and PEO solution with the weight ratio of 80:20 and 70:30 were prepared, and 2% weight of nano-hydroxyapatite was added. Nanofibers were prepared using the electrospinning method, and the morphology was studied using scanning electron microscopy (SEM). Afterwards, the BMSCs of mature rats were cultured on nanofibers and differentiated by adding a differentiation medium. The survival of the differentiated cells was evaluated at the end of the first, second, and third week using acridine orange staining, and the morphology of the differentiated cells exposed to nanofibers was assessed using SEM. <br />Results: The mean diameter of the nanofibers with the ratio of 80:20 was 150±17 nanometers. The differentiation of BMSCs into the osteoblast-like cells on nanofibers was confirmed using Alizarin red staining. The results indicated a significant decrease in the survival of the differentiated cells in the nanofiber groups by the end of the third week of differentiation compared to the control samples.<br />Conclusion: According to the results, BMSCs could be differentiated into osteoblast-like cells in the presence of the chitosan/PEO nanofibers containing nano-hydroxyapatite.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701The effects of indirect exposure of nanosilver on caspase-8 and caspase-9 levels in liver and brain of suckling rats1761821309910.22038/nmj.2019.06.00004ENMahnoosh FatemiDepartment of Biology, Falavarjan Branch, Islamic Azad University, Isfahan, IranJournal Article20190515Objective(s): The adverse health effects of nanosilver (AgNp) on adult animal models have been well documented. However, data is scarce regarding the toxic effects of AgNp on sensitive developmental stages. The present study aimed to investigate the effects of maternal milk exposure to AgNp on apoptosis induction in the liver and brain of the offspring of rats. <br />Materials and Methods: Lactating Wistar rats were intragastrically exposed to the vehicle (deionized water) or two doses of AgNp (25 and 100 mg/kg) for 21 days. Liver and brain samples were collected from the male pups of the mothers on postnatal day 21. The silver content and levels of caspase-8 and caspase-9 in the tissues were measured using the ICP-MS analysis and ELISA assay, respectively. For histopathological examinations, the tissue sections were stained using the hematoxylin-eosin (H&E) stain and examined by light microscopy.<br />Results: A significant, dose-dependent increase was observed in the silver content of the liver and brain of the pups and maternal milk exposed to AgNp. In addition, the level of caspase-9 significantly increased in the liver and brain in the pups exposed to the high dose of AgNp (100 mg/kg-1), while no significant changes were observed in the level of caspase-8 in the experimental groups compared to the controls. Histopathological studies also demonstrated tissue damage in the liver and brain of the pups exposed to the high dose of AgNp. <br />Conclusion: According to the results, lactational exposure to AgNp may induce apoptosis via the intrinsic pathway in the offspring tissues of rats. However, further investigation is required in order to document these findings.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701An artificial blood vessel fabricated by 3D printing for pharmaceutical application1831941318310.22038/nmj.2019.06.00005ENSaeid EsmaeiliNew Technologies Research Center, Amirkabir University of Technology, Tehran, 15875-4413, IranMaryam ShahaliDepartment of Quality Control, Research and Production Complex, Pasteur Institute of Iran, Tehran, IranAlireza KordjamshidiDepartment of Pharmacy, Eastern Mediterranean University, Gazimagusa, TRNC, via Mersin 10, TurkeyZahra TorkpoorStudents Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranFarshad NamdariDepartment of Urology, AJA University of Medical Sciences, Tehran, IranSaeed Saber- SamandariNew Technologies Research Center, Amirkabir University of Technology, Tehran, 15875-4413, IranMazyar Ghadiri NejadDepartment of Industrial Engineering, Eastern Mediterranean University, Gazimagusa, TRNC, Via Mersin 10, TurkeyAmirsalar KhandanNew Technologies Research Center, Amirkabir University of Technology, Tehran, 15875-4413, Iran0000-0001-8878-5233Journal Article20190521Objective(s): Cardiovascular diseases (CVDs) are the leading cause of mortality in the elderly. A common medical procedure for the treatment of CVDs is the replacement of the blocked or narrowed arteries, which is currently the optimal vascular transplant associated with autograft transplantation. In general, the saphenous veins and radial arteries in the mammary gland are considered to be the selective vessels for vascular substitution. In many cardiac patients, artificial blood vessels (ABVs) are not used for several reasons, including the age of the patient, small size of the veins, previous impressions, and abnormally. Therefore, the consideration of vascular substitute demands is inevitable, especially regarding vascular transplantation with very small diameters and availability of proper alternatives. The present study aimed to develop a novel artificial bio-composite blood vessel using polymer-reinforced and bioceramic nanoparticles. <br />Materials and Methods: The biomechanics and chemical properties of artificial vessels have been investigated to be used in coronary artery bypassing in atherosclerosis as a soft tissue engineering procedure. In this study, thermoplastic polyurethane (TPU) composed of nanocrystalline hydroxyapatite (HA) nanopowder was prepared using the extrusion technique to construct the ABVs. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to investigate the optimum specimen. An important feature of the ABVs was the ability to find the elastic modulus, wettability, and porosity of the veins, which were assessed by fused deposition modeling and 3D printing. <br />Results: The sample containing five wt% of HA had superior mechanical and biological features over the pure sample. <br />Conclusion: According to the results, the narrowed arteries composed of TPU composite with nanocrystalline HA nanopowder had proper chemical stability and mechanical characteristics.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701ShRNA-mediated knock-down of CD200 using the self-assembled nanoparticle-forming derivative of polyethylenimine1952061318110.22038/nmj.2019.06.00006ENBahman KhalvatiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, IranAli DehshahriDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-4458-1292Journal Article20190521Objective(s): ShRNA-mediated silencing strategy is considered to be a potent therapeutic approach. The present study aimed to assess the ability of the previously prepared polyethylenimine (PEI) derivative for the shRNA knock-down of the CD200 gene on the cells obtained from the patients with chronic lymphocytic leukemia (CLL). <br />Materials and Methods: Since there are several investigations regarding the role of CD200 over-expression in the progression of several malignancies (e.g., CLL), polyplexes were prepared using succinylated PEI and the plasmid encoding anti-CD200 shRNA. The ability of the nanoparticles for CD200 silencing at the levels of protein and mRNA, as well as the apoptotic effects induced by unmodified PEI and its derivative, were evaluated. <br />Results: Conjugation of succinic acid using the primary amines of PEI reduced the cell-induced toxicity of the polymer. Under such circumstances, 92.1% of the cells remained alive after treatment with the nanoparticles based on modified PEI. In addition, CD200 knock-down evaluations demonstrated a 50% reduction in the expression of the gene in the samples obtained from patients with CLL, while using the same formulation on the cells obtained from healthy donors decreased the CD200+ cells up to 10%. The results of CD200 silencing at the mRNA level revealed that the shRNA formulation could reduce the CD200 level in the cells of the patients by 3.2-6.06-fold relative to the cells transfected with non-effective, scrambled shRNA. <br />Conclusion: Our findings supported the application of succinylated PEI for the down-regulation of the CD200 gene in the upcoming attempts to develop nano-carriers for gene therapy.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701Application of near-infrared light intensity to determine normal and cancerous breast vessel contrast by gold nanoparticles2072131318410.22038/nmj.2019.06.00007ENParinaz MehnatiDepartment of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IranBahman AlipourMedical Radiation Sciences Research Team, Tabriz University of Medical Sciences, Tabriz, IranRoya SalehiDrug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, IranJournal Article20190521Objective(s): A novel technique for the early diagnosis of breast cancer involves the use of nanoparticles (NPs). The present study aimed to use gold NPs to assess the variations in light source transfer intensity. <br />Materials and Methods: Blood samples with hemoglobin (Hb) concentrations of ×1, ×2, and ×4 were used to simulate normal and cancerous conditions in the breast. Spherical gold NPs (SGNPs) and gold nanorods (GNRs) with various Hb concentrations were injected into the breast phantom, and the intensity of the light transmitted on the wavelength of 635 nanometers was measured. Transmission electron microscopy (TEM) images revealed that SGNPs and GNRs were prepared with a uniform particle shape.<br />Results: When the SGNPs were blended with the Hb concentrations of ×1, ×2, and ×4, the intensity of the passing light from the vessel was estimated to be 3.62, 2.40, and 1.64 mw, respectively. When GNRs were blended with the Hb concentrations of ×1, ×2, and ×4, the intensity changed to lower values 3.42, 2.13, and 1.98 mw, respectively. <br />Conclusion: According to the results, SGNPs and GNRs in normal and cancerous breast induced various passing intensities of Hb concentrations. In addition, the vascular contrast induced by GNRs was higher compared to SGNPs.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701Potential positive MRI contrast agent based on PVP-grafted superparamagnetic iron oxide nanoparticles with various repetition times2142221318510.22038/nmj.2019.06.00008ENMahmood NazarpoorDepartment of Medical Physics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran0000-0001-5635-8990Hassan FattahiComposite Research Center, Department of Materials and Manufacturing Technologies, Malek Ashtar University of Technology, Tehran, IranJournal Article20190521Objective(s): The present study aimed to evaluate the capability of synthesized and modified superparamagnetic iron oxide nanoparticles (SPIONs) as the positive contrast agent in magnetic resonance imaging (MRI) by investigating the effect of repetition time (TR) on the MRI signal intensity. <br />Materials and Methods: SPIONs were synthesized using the co-precipitation method, and their surface was successfully modified with biocompatible poly (N-vinylpyrrolidone) (PVP). The effect of TR on the signal intensity (SI) of the PVP-grafted SPIONs was assessed in the spin-echo T1-weighted MRI images. <br />Results: The results indicated the maximum SI at the concentration of 400 µmol Fe/l with the TR of 800-2,200 milliseconds. Moreover, the maximum SI was observed at the concentration of 75 µmol Fe/l, where TR was within the range of 2,900-6,400 milliseconds. <br />Conclusion: According to the results, in addition to their capability as negative MRI contrast agents, PVP-grafted SPIONs could be preferred positive contrast agents with specific imaging parameters and have the potential application for early cancer diagnosis and perfusion measurements.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701Antibacterial and anti-biofilm effects of microwave-assisted biologically synthesized zinc nanoparticles2232311308510.22038/nmj.2019.06.00009ENMojtaba ShakibaieDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, IranHerbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, IranFatemeh Alipour-Esmaeili-AnariStudent Research Committee, School of Pharmacy, Kerman University of Medical Sciences, Kerman, IranMahboubeh Adeli-SardouHerbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, IranDepartment of Biotechnology, Institute of Science, High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran0000-0002-3131-1202Atefeh AmeriPharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IranMohsen DoostmohammadiPharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IranHamid ForootanfarDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, IranPharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran0000-0003-2072-421XAlieh AmeriDepartment of Medicinal Chemistry, School of Pharmacy, Kerman University of Medical Sciences, Kerman, IranJournal Article20190515Objective(s): The present study aimed to investigate the antibacterial and anti-biofilm potential of the non-oxidized form of zinc nanoparticles (Zn NPs) prepared by a ‘green approach’ using the Lavandula vera extract with microwave irradiation.<br />Materials and Methods: After synthesis of Zn NPs, the microdilution and disk diffusion methods was applied for antimicrobial evaluation followed by anti-biofilm activity measurement using crystal violet colorimetric assay procedure.<br />Results: The obtained results demonstrated the production of spherical Zn NPs within the size range of 30-80 nanometers. The measured minimum inhibitory concentration of the Zn NPs and ZnSO4 against the biofilm-producing and clinically isolated pathogens of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis was estimated to be more than 2560 µg/ml. In addition, a non-significant increase (P>0.05) was observed in the antibacterial activity against methicillin-resistant S. aureus after the addition of the Zn NPs (500 µg/disk) to the antibiotic discs containing tobramycin, erythromycin, tetracycline, azithromycin, and kanamycin compared to ZnSO4. On the other hand, the Zn NPs significantly decreased the biofilm formation of P. mirabilis compared to P. aeruginosa (P<0.05). Biofilm formation by S. aureus also reduced to 68.3±2.1% in the presence of the Zn NPs (640 µg/ml), which was considered significant compared to P. mirabilis and P. aeruginosa at the same concentration (P<0.05). <br />Conclusion: To sum up, the biofilm inhibitory activity of Zn NPs at higher concentrations than 160 µg/ml against S. aureus and P. mirabilis was more significant compared to the inhibitory effects of ZnSO4. However, further investigations are required in order to determine the antibacterial and anti-biofilm mechanism of Zn NPs.Mashhad University of Medical SciencesNanomedicine Journal2322-30496320190701Effects of combined 5-Fluorouracil and ZnO NPs on human breast cancer MCF-7 Cells: P53 gene expression, Bcl-2 signaling pathway, and invasion activity2322401311110.22038/nmj.2019.06.000010ENSafoura HoseinzadehClinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranElham RaeisiDepartment of Medical Physics and Radiology, Shahrekord University of Medical Sciences, Shahrekord, Iran0000-0003-3934-0398Yves LemoigneInstitute for Medical Physics, Ambilly, FranceEsfandiar HeidarianClinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran0000-0002-4701-144XJournal Article20190518Objective(s): The significant contribution of nanoparticles to cancer treatment has attracted therapeutic attention. The present study aimed to evaluate the synergistic effects of 5-fluorouracil (5-FU) and zinc oxide nanoparticles (ZnO NPs) as multimodal drug delivery on human breast cancer MCF-7 cells.<br />Materials and Methods: In this in-vitro study, the impact of 5-FU and ZnO NPs in the single or combined forms was evaluated on cell viability, colony formation, apoptosis, p53 gene expression, and Bcl-2 signaling protein in MCF-7 breast cancer cell line using several techniques, such as MTT, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot.<br />Results: In this study, 5-FU combined with ZnO NPs showed synergistic effects against MCF-7 within 48 hours. In addition, the combination of 5-FU and ZnO NPs at the respective concentrations of 1 µM and 45 µg/ml exhibited significant apoptosis (79.53%), p53 gene expression (3.6 folds), reduction of cell invasion (9.82%), and plating efficiency (5%), thereby leading to the significant reduction of cell viability (40±0.9%) and decreased Bcl-2 anti-apoptotic protein relative to untreated control cells. <br />Conclusion: According to the results, the synergistic effects of combined ZnO NPs and 5-FU on MCF-7 human breast cancer cells were exerted via Bcl-2 inhibition and the up-regulation of p53 expression.