Search

Mohammadreza Abdihaji,1,* Masoumeh Mirzaei Chegeni,2,* Alireza Hadizadeh,3 Negar Farrokhzad,4 Zahra Kheradmand,5 Parastoo Fakhrfatemi,6 Fardad Faress,7 Kasra Moeinabadi-Bidgoli,8 Hassan Noorbazargan,9 Ebrahim Mostafavi10,11 1Department of Biology, The Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN, USA; 2Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; 3Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 5Department of Agriculture, Islamic Azad University Maragheh Branch, Maragheh, Iran; 6Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 7Department of Business, Data Analysis, The University of Texas Rio Grande Valley (UTRGV), Edinburg, TX, USA; 8Basic and Molecular Epidemiology of Gastroenterology Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 9Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 10Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; 11Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA*These authors contributed equally to this workCorrespondence: Ebrahim Mostafavi, Email ebimsv@stanford.edu; ebi.mostafavi@gmail.comIntroduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region.Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box–Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays.Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays.Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells.Graphical Abstract: Keywords: herbal anticancer drug, thymol, cancerous cell lines, pH-dependent release, niosome, polyvinyl alcohol, apoptosis

Saeedeh Ahmadi,1 Mahmoud Seraj,2 Mohsen Chiani,1 Seyedayin Hosseini,3 Saba Bazzazan,4 Iman Akbarzadeh,1 Samaneh Saffar,4 Ebrahim Mostafavi5,6 1Department of Nano Biotechnology, New Technology Research Group, Pasteur Institute of Iran, Tehran, Iran; 2Integrative Research Laboratory, Islamic Azad University of Medical Sciences, Tehran, Iran; 3School of Medicine, Sh Beheshti University of Medical Sciences, Tehran, Iran; 4Core Facility Lab, Pasteur Institute of Iran, Tehran, Iran; 5Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA; 6Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USACorrespondence: Ebrahim Mostafavi, Email ebimsv@stanford.edu, ebi.mostafavi@gmail.com; Mohsen Chiani, Email chiani@pasteur.ac.irIntroduction: Breast cancer is among the most prevalent mortal cancers in women worldwide. In the present study, an optimum formulation of letrozole, letrozole-loaded niosome, and empty niosome was developed, and the anticancer effect was assessed in in vitro MCF-7, MCF10A and MDA-MB-231 breast cancer cell lines.Materials and Methods: Various niosomal formulations of letrozole were fabricated through thin-film hydration method and characterized in terms of size, polydispersity index (PDI), morphology, entrapment efficiency (EE%), release kinetics, and stability. Optimized niosomal formulation of letrozole was achieved by response surface methodology (RSM). Antiproliferative activity and the mechanism were assessed by MTT assay, quantitative real-time PCR, and flow cytometry. Furthermore, cellular uptake of optimum formulation was evaluated by confocal electron microscopy.Results: The formulated letrozole had a spherical shape and showed a slow-release profile of the drug after 72 h. The size, PDI, and eEE% of nanoparticles showed higher stability at 4°C compared with 25°C. The drug release from niosomes was in accordance with Korsmeyer–Peppa’s kinetic model. Confocal microscopy revealed the localization of drug-loaded niosomes in the cancer cells. MTT assay revealed that all samples exhibited dose-dependent cytotoxicity against breast cancer cells. The IC50 of mixed formulation of letrozole with letrozole-loaded niosome (L + L3) is the lowest value among all prepared formulations. L+L3 influenced the gene expression in the tested breast cancer cell lines by down-regulating the expression of Bcl 2 gene while up-regulating the expression of p53 and Bax genes. The flow cytometry results revealed that L + L3 enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cell lines compared with the letrozole (L), letrozole-loaded niosome (L3), and control sample.Conclusion: Results indicated that niosomes could be a promising drug carrier for the delivery of letrozole to breast cancer cells.Graphical Abstract: Keywords: breast cancer, niosome, letrozole, drug delivery system, anticancer

Sahar Porrang,1,2 Soodabeh Davaran,3,4 Nader Rahemi,1,2 Somaiyeh Allahyari,1,2 Ebrahim Mostafavi5,6 1Chemical Engineering Faculty, Sahand University of Technology, Tabriz, Iran; 2Environmental Engineering Research Centre, Sahand University of Technology, Tabriz, Iran; 3Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran; 4Research Centre for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; 5Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA; 6Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USACorrespondence: Ebrahim Mostafavi, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA, Email ebimsv@stanford.edu; ebi.mostafavi@gmail.com Nader Rahemi, Sahand University of Technology, Tabriz, Iran, Tel +98-41-33459100, Email n_rahemi@sut.ac.irAbstract: The application of mesoporous silica nanoparticles (MSNs) is ubiquitous in various sciences. MSNs possess unique features, including the diversity in manufacturing by different synthesis methods and from different sources, structure controllability, pore design capabilities, pore size tunability, nanoparticle size distribution adjustment, and the ability to create diverse functional groups on their surface. These characteristics have led to various types of MSNs as a unique system for drug delivery. In this review, first, the synthesis of MSNs by different methods via using different sources were studied. Then, the parameters affecting their physicochemical properties and functionalization have been discussed. Finally, the last decade’s novel strategies, including surface functionalization, drug delivery, and cancer treatment, based on the MSNs in drug delivery and cancer therapy have been addressed.Graphical Abstract: Keywords: mesoporous silica nanoparticles, synthesis method, natural sources, synthetic sources, drug delivery, controlled release

AimDendrimers dendritic structural design holds vast promises, predominantly for drug delivery, owing to their unique properties. Dendritic architecture is widespread topology found in nature and offers development of specific properties of chemical substances. Dendrimers are an ideal delivery vehicle candidate for open study of the effects of polymer size, charge, and composition on biologically relevant properties such as lipid bilayer interactions, cytotoxicity, bio-distribution, internalization, blood plasma retention time, and filtration. This article reviews role of dendrimers in advanced drug delivery and biomedical applications.

Milad Ashrafizadeh,1 Alan Prem Kumar,2,3 Amir Reza Aref,4,5 Ali Zarrabi,6 Ebrahim Mostafavi7,8 1Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, 34956, Istanbul, Turkey; 2NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; 3Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore; 4Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 5Translational Sciences, Xsphera Biosciences Inc., Boston, MA, 02210, USA; 6Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey; 7Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA; 8Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USACorrespondence: Ebrahim Mostafavi, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA, Email ebimsv@stanford.edu; ebi.mostafavi@gmail.com Ali Zarrabi, Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey, Email ali.zarrabi@istinye.edu.trAbstract: Diabetes mellitus (DM) is among the chronic metabolic disorders that its incidence rate has shown an increase in developed and wealthy countries due to lifestyle and obesity. The treatment of DM has always been of interest, and significant effort has been made in this field. Exosomes belong to extracellular vesicles with nanosized features (30– 150 nm) that are involved in cell-to-cell communication and preserving homeostasis. The function of exosomes is different based on their cargo, and they may contain lipids, proteins, and nucleic acids. The present review focuses on the application of exosomes in the treatment of DM; both glucose and lipid levels are significantly affected by exosomes, and these nanostructures enhance lipid metabolism and decrease its deposition. Furthermore, exosomes promote glucose metabolism and affect the level of glycolytic enzymes and glucose transporters in DM. Type I DM results from the destruction of β cells in the pancreas, and exosomes can be employed to ameliorate apoptosis and endoplasmic reticulum (ER) stress in these cells. The exosomes have dual functions in mediating insulin resistance/sensitivity, and M1 macrophage-derived exosomes inhibit insulin secretion. The exosomes may contain miRNAs, and by transferring among cells, they can regulate various molecular pathways such as AMPK, PI3K/Akt, and β-catenin to affect DM progression. Noteworthy, exosomes are present in different body fluids such as blood circulation, and they can be employed as biomarkers for the diagnosis of diabetic patients. Future studies should focus on engineering exosomes derived from sources such as mesenchymal stem cells to treat DM as a novel strategy.Keywords: diabetes mellitus, insulin resistance, exosome, glucose uptake, lipid metabolism

Maryam Zarghami Dehaghani,1 Farrokh Yousefi,2 Farzad Seidi,1 S Mohammad Sajadi,3,4 Navid Rabiee,5 Sajjad Habibzadeh,6 Amin Esmaeili,7 Amin Hamed Mashhadzadeh,8 Christos Spitas,8 Ebrahim Mostafavi,9,10 Mohammad Reza Saeb11 1Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources and Joint International Research Lab of Lignocellulosic Functional Materials, Nanjing Forestry University, Nanjing, 210037, People’s Republic of China; 2Department of Physics, University of Zanjan, Zanjan, 45195-313, Iran; 3Department of Nutrition, Cihan University-Erbil, Erbil, Iraq; 4Department of Phytochemistry, SRC, Soran University, Soran, Iraq; 5Department of Physics, Sharif University of Technology, Tehran, Iran; 6Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, 1591639675, Iran; 7Department of Chemical Engineering, School of Engineering Technology and Industrial Trades, College of the North Atlantic — Qatar, Doha, Qatar; 8Mechanical and Aerospace Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Nur-Sultan, 010000, Kazakhstan; 9Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; 10Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; 11Department of Polymer Technology, Faculty of Chemistry, Gdańsk University of Technology, Gdańsk, 80-233, PolandCorrespondence: Amin Hamed MashhadzadehMechanical and Aerospace Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Nur-Sultan, 010000, KazakhstanEmail amin.hamed.m@gmail.com; amin.hamedmashhadzadeh@nu.edu.kzEbrahim MostafaviStanford Cardiovascular Institute, Stanford University School of Medicine, Biomedical Innovation Building, 240 Pasteur Drive, Palo Alto, Stanford, CA 94304, USAEmail ebimsv@Stanford.edu; ebi.mostafavi@gmail.comIntroduction: Carbon nanotubes (CNTs) have been widely employed as biomolecule carriers, but there is a need for further functionalization to broaden their therapeutic application in aqueous environments. A few reports have unraveled biomolecule–CNT interactions as a measure of response of the nanocarrier to drug-encapsulation dynamics.Methods: Herein, the dynamics of encapsulation of the antimicrobial peptide HA-FD-13 (accession code 2L24) into CNTs and hydroxylated CNTs (HCNTs) is discussed.Results: The van der Waals (vdW) interaction energy of CNT–peptide and HCNT–peptide complexes decreased, reaching − 110.6 and − 176.8 kcal.Mol− 1, respectively, once encapsulation of the peptide inside the CNTs had been completed within 15 ns. The free energy of the two systems decreased to − 43.91 and − 69.2 kcal.Mol− 1 in the same order.Discussion: The peptide was encased in the HCNTs comparatively more rapidly, due to the presence of both electrostatic and vdW interactions between the peptide and HCNTs. However, the peptide remained encapsulated throughout the vdW interaction in both systems. The negative values of the free energy of the two systems showed that the encapsulation process had occurred spontaneously. Of note, the lower free energy in the HCNT system suggested more stable peptide encapsulation.Keywords: drug delivery, hydroxylation, carbon nanotubes, molecular dynamic simulation, encapsulation, antimicrobial peptide

Maryam Zarghami Dehaghani,1,* Babak Bagheri,2,* Farrokh Yousefi,3 Abbasali Nasiriasayesh,4 Amin Hamed Mashhadzadeh,5 Payam Zarrintaj,6 Navid Rabiee,7 Mojtaba Bagherzadeh,7 Vanessa Fierro,8 Alain Celzard,8 Mohammad Reza Saeb,5 Ebrahim Mostafavi9,10 1School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 2Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; 3Department of Physics, University of Zanjan, Zanjan, 45195-313, Iran; 4Industrial Management Institute, Tehran, Iran; 5Center of Excellence in Electrochemistry, School of Chemistry, College of Science, University of Tehran, Tehran, 14155-6455, Iran; 6School of Chemical Engineering, Oklahoma State University, Stillwater, OK, 74078, USA; 7Department of Chemistry, Sharif University of Technology, Tehran, Iran; 8Université De Lorraine, CNRS, IJL, Epinal, 88000, France; 9Stanford Cardiovascular Institute, Stanford, CA, USA; 10Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA*These authors contributed equally to this workCorrespondence: Ebrahim MostafaviStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USAEmail ebimsv@stanford.eduAmin Hamed MashhadzadehCenter of Excellence in Electrochemistry, School of Chemistry, College of Science, University of Tehran, Tehran, 14155-6455, IranEmail amin.hamed.m@gmail.comIntroduction: Nanotube-based drug delivery systems have received considerable attention because of their large internal volume to encapsulate the drug and the ability to penetrate tissues, cells, and bacteria. In this regard, understanding the interaction between the drug and the nanotube to evaluate the encapsulation behavior of the drug in the nanotube is of crucial importance.Methods: In this work, the encapsulation process of the cationic antimicrobial peptide named cRW3 in the biocompatible boron nitride nanotube (BNNT) was investigated under the Canonical ensemble (NVT) by molecular dynamics (MD) simulation.Results: The peptide was absorbed into the BNNT by van der Waals (vdW) interaction between cRW3 and the BNNT, in which the vdW interaction decreased during the simulation process and reached the value of − 142.7 kcal·mol− 1 at 4 ns.Discussion: The increase in the potential mean force profile of the encapsulated peptide during the pulling process of cRW3 out of the nanotube showed that its insertion into the BNNT occurred spontaneously and that the inserted peptide had the desired stability. The energy barrier at the entrance of the BNNT caused a pause of 0.45 ns when half of the peptide was inside the BNNT during the encapsulation process. Therefore, during this period, the peptide experienced the weakest movement and the smallest conformational changes.Keywords: boron nitride nanotube, drug delivery, antimicrobial peptide, molecular dynamic simulation, encapsulation

Hossein Zare,1,2 Sepideh Ahmadi,3,4 Amir Ghasemi,5 Mohammad Ghanbari,6 Navid Rabiee,7 Mojtaba Bagherzadeh,7 Mahdi Karimi,8– 11 Thomas J Webster,12 Michael R Hamblin,13 Ebrahim Mostafavi12,14,15 1Advances Nanobiotechnology and Nanomedicine Research Group (ANNRG), Iran University of Medical Sciences, Tehran, Iran; 2Biomaterials Group, Materials Science and Engineering Department, Iran University of Science and Technology, Tehran, Iran; 3Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Engineering, Durham University, Durham, DH1 3LE, United Kingdom; 6School of Metallurgy and Materials Engineering, University of Tehran, Tehran, Iran; 7Department of Chemistry, Sharif University of Technology, Tehran, Iran; 8Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; 9Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; 10Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran; 11Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, MA, Iran; 12Applied Biotechnology Research Centre, Tehran Medical Science, Islamic Azad University, Tehran, MA, Iran; 13Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa; 14Stanford Cardiovascular Institute, Stanford, CA, USA; 15Department of Medicine, Stanford University School of Medicine, Stanford, CA, USACorrespondence: Ebrahim MostafaviStanford Cardiovascular Institute, Stanford University School of Medicine, Biomedical Innovation Building, 240 Pasteur Dr, Palo Alto, CA, 94304, USAEmail ebimsv@stanford.eduMichael R HamblinLaser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South AfricaEmail hamblin.lab@gmail.comAbstract: The unique properties of carbon nanotubes (CNTs) (such as their high surface to volume ratios, enhanced conductivity and strength, biocompatibility, ease of functionalization, optical properties, etc.) have led to their consideration to serve as novel drug and gene delivery carriers. CNTs are effectively taken up by many different cell types through several mechanisms. CNTs have acted as carriers of anticancer molecules (including docetaxel (DTX), doxorubicin (DOX), methotrexate (MTX), paclitaxel (PTX), and gemcitabine (GEM)), anti-inflammatory drugs, osteogenic dexamethasone (DEX) steroids, etc. In addition, the unique optical properties of CNTs have led to their use in a number of platforms for improved photo-therapy. Further, the easy surface functionalization of CNTs has prompted their use to deliver different genes, such as plasmid DNA (PDNA), micro-RNA (miRNA), and small interfering RNA (siRNA) as gene delivery vectors for various diseases such as cancers. However, despite all of these promises, the most important continuous concerns raised by scientists reside in CNT nanotoxicology and the environmental effects of CNTs, mostly because of their non-biodegradable state. Despite a lack of widespread FDA approval, CNTs have been studied for decades and plenty of in vivo and in vitro reports have been published, which are reviewed here. Lastly, this review covers the future research necessary for the field of CNT medicine to grow even further.Keywords: drug delivery, gene delivery, carbon nanotube, precision medicine

Muthupandian Saravanan,1 Hossein Vahidi,2 David Medina Cruz,3,4 Ada Vernet-Crua,3,4 Ebrahim Mostafavi,3,4 Ryan Stelmach,3 Thomas J Webster,3,4 Mohammad Ali Mahjoub,5 Masoumeh Rashedi,6 Hamed Barabadi2 1Department of Medical Microbiology and Immunology, Division of Biomedical Science, School of Medicine, College of Health Sciences, Mekelle University, Mekelle 1871, Ethiopia; 2Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 4Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA; 5Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 6Student Research Committee, School of Medicine, Gonabad University of Medical Sciences, Gonabad, IranCorrespondence: Thomas J WebsterDepartment of Chemical Engineering, Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USATel +1 617 373 6585Email th.webster@neu.eduHamed BarabadiDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, PO Box 14155-6153, Tehran 1991953381, IranTel/Fax +982188665250Email barabadi@sbmu.ac.irAbstract: Breast cancer remains as a concerning global health issue, being the second leading cause of cancer deaths among women in the United States (US) in 2019. Therefore, there is an urgent and substantial need to explore novel strategies to combat breast cancer. A potential solution may come from the use of cancer nanotechnology, an innovative field of study which investigates the potential of nanomaterials for cancer diagnosis, therapy, and theranostic applications. Consequently, the theranostic functionality of cancer nanotechnology has been gaining much attention between scientists during the past few years and is growing exponentially. The use of biosynthesized gold nanoparticles (AuNPs) has been explored as an efficient mechanism for the treatment of breast cancer. The present study supposed a global systematic review to evaluate the effectiveness of biogenic AuNPs for the treatment of breast cancer and their anticancer molecular mechanisms through in vitro studies. Online electronic databases, including Cochrane, PubMed, Scopus, Web of Science, Science Direct, ProQuest, and Embase, were searched for the articles published up to July 16, 2019. Our findings revealed that plant-mediated synthesis was the most common approach for the generation of AuNPs. Most of the studies reported spherical or nearly spherical-shaped AuNPs with a mean diameter less than 100 nm in size. A significantly larger cytotoxicity was observed when the biogenic AuNPs were tested towards breast cancer cells compared to healthy cells. Moreover, biogenic AuNPs demonstrated significant synergistic activity in combination with other anticancer drugs through in vitro studies. Although we provided strong and comprehensive preliminary in vitro data, further in vivo investigations are required to show the reliability and efficacy of these NPs in animal models.Keywords: cancer nanotechnology, nanotoxicity, gold nanoparticles, anti-cancer

Hamed Amani,1,2,* Ebrahim Mostafavi,3,* Mahmoud Reza Alebouyeh,4,* Hamidreza Arzaghi,5 Abolfazl Akbarzadeh,6 Hamidreza Pazoki-Toroudi,7 Thomas J Webster3 1Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; 2Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 3Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 4Anesthesia Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 5Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran; 6Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; 7Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran*These authors contributed equally to this workCorrespondence: Thomas J WebsterDepartment of Chemical Engineering, Northeastern University, Boston, MA, USAEmail th.webster@neu.eduHamidreza Pazoki-ToroudiPhysiology Research Center and Department of Physiology, Iran University of Medical Sciences, P.O. Box 14515-763, Tehran, IranFax +98-21-88675760Email pazoki49@gmail.comIntroduction: This study was conducted to evaluate OX26-PEG-coated gold nanoparticles (GNPs) (OX26@GNPs) as a novel targeted nanoparticulate system on cell survival after ischemic stroke.Materials and methods: Dynamic light scattering (DLS), zeta sizer, and transmission electron microscopy (TEM) were performed to characterize the OX26@GNPs. The effect of OX26@GNPs on infarct volume, neuronal loss, and necroptosis was evaluated 24 h after reperfusion using 2, 3,5-Triphenyltetrazolium chloride (TTC) staining, Nissl staining and Western blot assay, respectively.Results: Conjugation of OX26-PEG to the surface of the 25 nm colloidal gold particles increased their size to 32±2 nm, while a zeta potential change of −40.4 to 3.40 mV remarkably increased the stability of the nanoparticles. Most importantly, OX26@GNPs significantly increased the infarcted brain tissue, while bare GNPs and PEGylated GNPs had no effect on the infarct volume. However, our results indicated an extension of necroptotic cell death, followed by cell membrane damage.Conclusion: Collectively, our results showed that the presently formulated OX26@GNPs are not suitable nanocarriers nor contrast agents under oxidative stress for the diagnosis and treatment of ischemic stroke. Moreover, our findings suggest that the cytotoxicity of GNPs in the brain is significantly associated with their surface charge.Keywords: targeted delivery, gold nanoparticles, necroptosis, surface charge, oxidative stress, cytotoxicity

Rodents act as reservoirs, intermediate hosts, or definitive hosts for various zoonotic helminths. Parasitic diseases are among the critical factors affecting the survival and composition of wild rodent populations. Wild rodents share their habitat with domestic free-grazing animals, mainly sheep, stray dogs, and cats, which allows the transmission of helminth infections, such as Toxocara and Trichinella, to these animals. This study investigated the helminth parasite fauna of wild rodents in East Azerbaijan province, north-western Iran, and discussed the possibility of parasite transmission among wild rodents. A total of 204 rodents of 17 different species (spp.) were collected in north-western Iran. Information about the genus, developmental stage, and rodent spp. was recorded for each animal. The gastrointestinal tract, liver, and diaphragm were examined for the presence of helminths. The recovered specimens were identified based on references. The prevalence rate of helminth infection among the captured rodents was 67.16%. Meriones persicus (M. persicus) showed the highest infection and diversity rates. This spp. harbored the zoonotic helminth Capillaria hepatica and some spp. belonging to the genera Toxocara, Syphacia, and Hymenolepis. M. persicus specimens from mountainous areas showed the highest infection rate. This study aimed at evaluating the potential role of wild rodent spp. as reservoirs of helminth infection in East Azerbaijan province, Iran. M. persicus was the most common spp. in our study and represented a higher proportion of the infected rodents in terms of helminth diversity and frequency. Harboring zoonotic helminths, M. persicus represents a health risk. Further studies are recommended to evaluate the prevalence of these parasites in the human community and inform people concerned about the risk of disease transmission to humans through rodents. [ABSTRACT FROM AUTHOR]

Study and analytical comparision of works of the nobles shows their impressions to each other, in addition to can be useful to ranking of thinking progresses of culture.” Naserkhosro” and “Molavi” create rich works that were imitated several times. Purpose of this article is showing similarities of” Masnavi” of “Molavi “ and “Wajhi din” of “Naserkhosro”.These cases include two groups worldviews and parables. Some similarities : necessity of obedience of authorities, importance of inner part and sense, high rank of knowledge,…