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    Dendrimer-like supramolecular nanovalves based on polypseudorotaxane and mesoporous silica-coated magnetic graphene oxide: a potential pH-sensitive anticancer drug carrier

    , Article Supramolecular Chemistry ; Volume 28, Issue 7-8 , 2016 , Pages 624-633 ; 10610278 (ISSN) Pourjavadi, A ; Mazaheri Tehrani, Z ; Shakerpoor, A ; Sharif University of Technology
    Taylor and Francis Ltd 
    Abstract
    In the present research, two types of drug carriers based on mesoporous silica-coated magnetic graphene oxide, Fe3O4@GO@mSiO2, were synthesised and the pH-responsive behaviour for doxorubicin release was investigated. One type of the carrier was dendrimer-like multi ethylene amine grafted on Fe3O4@GO@mSiO2 and the other was dendrimer-like supramolecular polypseudorotaxane. Herein, α-cyclodextrin was used in the structure of supramolecular nanoparticles as a gatekeeper to inhibit the drug from escaping at neutral pH (the pH of healthy tissue). The drug release profile showed that the supramolecular nanocarrier was more sensitive to the pH changes. The content of drug release was about 100% at... 

    Albumin-graphene oxide conjugates; Carriers for anticancer drugs

    , Article RSC Advances ; Vol. 4, issue. 62 , July , 2014 , pp. 33001-33006 ; ISSN: 20462069 Jokar, S ; Pourjavadi, A ; Adeli, M ; Sharif University of Technology
    Abstract
    In order to improve its biological properties, graphene oxide can be modified with hydrophilic polymers. Therefore, in this study, the surface of graphene oxide was modified with polyethylene glycol and albumin by covalent methods. In the subsequent step, paclitaxel which is a hydrophobic anticancer drug was loaded onto the surface of the functionalized graphene by π-π interactions. The synthesis of the nanocarrier and its interaction with paclitaxel were evaluated by FT-IR, CD, TEM, UV, AFM, DLS and fluorescence experiments. Release of the loaded drug from albumin-graphene conjugate was investigated at pH 5.4, 6.8 and 7.4  

    DFT study on Thiotepa and Tepa interactions with their DNA receptor

    , Article Structural Chemistry ; Volume 24, Issue 1 , February , 2013 , Pages 1-11 ; 10400400 (ISSN) Torabifard, H ; Fattahi, A ; Sharif University of Technology
    2013
    Abstract
    Thiotepa (N,N′,N″-triethylenethiophosphoramide) and its major metabolite (Tepa) as trifunctional alkylating agents has recently been used in cancer therapy. In vivo and vitro studies show the possible pathways of alkylation of DNA by Thiotepa and Tepa. Two pathways are suggested, but the main pathway of mechanism remains unclear. In pathway 1, forming cross-links with DNA molecules can be carried out via two different mechanisms. In first mechanism, these agents undergo the ring opening reaction which is initiated by protonating aziridine, which then becomes the main target of nucleophilic attack by the N7-Guanine of DNA. The second probable mechanism is ring opening of aziridyl group by... 

    Design of Drug Structures in Order to Inhibit Met, A Member of the Tyrosine Phosphatase Protein Family to Replace Existing Drugs

    , M.Sc. Thesis Sharif University of Technology Zeinal, Mostafa (Author) ; Fattahi, Alireza (Supervisor)
    Abstract
    This project aims to design a novel structure that can inhibit the activitvation of the c-Met enzyme using amino acids and sugars building blocks. The c-Met enzyme is a receptor tyrosine kinase that plays a significant role in several biological activities such as cell proliferation, survival, and invasion. Abnormal activity of the enzyme is linked to the progression of various types of cancer, including breast, lung, liver, and stomach cancer. The proposed sugar amino acid conjugate structures is expected to increase stability amino acids and dipeptides in the physiological environment, improve membrane permeability via active transport mechanism, and reduce toxicity and side effects by... 

    Synthesis of Pyrene-Based Supramolecular Nanomaterials and Investigation of its Cellular Toxicity of Antitumor and Activities

    , M.Sc. Thesis Sharif University of Technology Eskandari, Mohammad (Author) ; Pourjavadi, Ali (Supervisor)
    Abstract
    In this work, pH sensitive supramolecular shuttles consisting of carbon nanotube-graft-pyrene (CNT-graft-PYR) and hyperbranched polyglycerol with β-cyclodextrin core (β-CD-graft-PG) were synthesized and characterized. Supramolecular systems (PG/CNT/S) were able to load and transport doxorubicin in aqueous solutions. While PG/CNT/S were soluble in phosphate buffer pH 7, they were divided to their individual moieties in pH 5 and therefore CNTs containing staked doxorubicin molecules were precipitated  

    Synthesis of Graphene Oxide Coating with Hydrophilic Polymers as Paclitaxel Anticancer Drug Delivery Systems

    , M.Sc. Thesis Sharif University of Technology Jokar, Safura (Author) ; Adeli, Mohsen (Supervisor) ; Poujavadi, Ali (Co-Advisor)
    Abstract
    Nowadays, there is no perfect drug delivery for cancer therapy; also the healthy tissues can be damaged more than tumor tissues. To resolve this problem, the new drug delivery system based on nanostructured materials is useful. Graphene oxide (GO) is one of the most important graphene derivatives and a potential candidate for drug delivery system. It has high specific surface area so that it can load and deliver the drug in a good manner. Hydrophobicity of graphene restricts its application in nanomedicine. In order to improve its solubility in water, graphene should be modified by hydrophilic polymers. Therefore, in this study, in order to activate the graphene surface and increase its... 

    Targeted Delivery of Curcumin by Mesoporous Silica Nanoparticle Coated with Liposome

    , M.Sc. Thesis Sharif University of Technology Hedayati, Mohammad Hassan (Author) ; Abdekhodaie, Mohammad Jafar (Supervisor) ; Akbari, Hamid (Supervisor)
    Abstract
    Several studies based on anti- cancer, anti- metastatic and anti- tumor effects of curcumin have been reported . Besides these benefits, the therapeutic efficacy of curcumin is limited due to its poor aqueous solubility, extensive first-pass metabolism, inadequate tissue absorption and degradation at alkaline pH, which severely diminishes its bioavailability. In this project we seek to solve some of the problems with nanoscience to work more effectively. In the past decade, mesoporous silica nanoparticles (MSNs) have found widespread application as controlled drug delivery systems. Recent reports on the design of capped and gated MSN-based systems have shown promise in preventing premature... 

    Investigate Laboratory Production of Hydroxyurea

    , M.Sc. Thesis Sharif University of Technology Nejati, Poorya (Author) ; Bastani, Dariush (Supervisor) ; Seifkordi, Ali Akbar (Supervisor) ; Zegordi, Elahe (Co-Advisor)
    Abstract
    Hydroxyurea is an anticancer drug that is commonly used to treat chronic myeloid leukemia (white blood cell cancer in bone marrow), polycythemia vera (red blood cell cancer), sickle cell anemia, solid tumors, and in particular leukemia. In this research, in addition to analyzing all available methods for synthesis of hydroxyurea, the most economical method for synthesis of hydroxyurea which is Hantzsch method was chosen; then we synthesized hydroxyurea crystals using a precipitation or crystallization process. To do so, two hydroxylamine hydrochloride and potassium cyanate reactants have been used in the semi batch reactor. Since the reaction efficiency and purity of the synthesized... 

    Extracellular L-Asparaginase Production in Candida Utilis: Production and Activity Determination Conditions

    , M.Sc. Thesis Sharif University of Technology Mahdinia, Ehsan (Author) ; Vosoughi, Manouchehr (Supervisor) ; Alemzadeh, Iran (Co-Advisor)
    Abstract
    L-Asparaginase has two major uses. For decades it has been known and used as an antitumor agent. Besides, it has been introduced as a food processing aid in the last trench against acrylamide formation in foods. Here, we have produced extracellular L-Asparaginase from Candida utilis and studied the parameters surrounding its production. Thus, two species of yeast were cross-examined: Saccharomyces cerevisiae (BBRC 30006) and Candida utilis (ATCC 9950). Moreover, the most suitable method for detecting and determining L-Asparaginase activity was investigated and selected for this purpose which is via L-Aspartate determination with Hydroxylamine. Furthermore, six deferent parameters of... 

    Investigation of Anticancer Drug Metabolism in Saccharomyces Cerevisiae as a Drug Resistance Model

    , M.Sc. Thesis Sharif University of Technology Hamed Rahimi, Reza (Author) ; Yaghmaei, Soheila (Supervisor) ; Sardari, Soroush (Supervisor)
    Abstract
    Cancer is a life-threatening group of diseases that arises from the uncontrolled growth and division of cells in the body. Treatment options for cancer include surgery, chemotherapy, radiation therapy, immunotherapy, targeted therapy, and hormone therapy. However, resistance to anticancer drugs can develop through a variety of mechanisms, such as the upregulation of drug efflux pumps and alterations in DNA repair mechanisms. One common mechanism of drug resistance is through changes in metabolism, where cancer cells switch to alternative metabolic pathways to survive and evade the effects of anticancer drugs. The development of new drugs targeting specific molecules and pathways involved in... 

    Edge-functionalization of graphene by polyglycerol; A way to change its flat topology

    , Article Polymer (United Kingdom) ; Volume 54, Issue 12 , 2013 , Pages 2917-2925 ; 00323861 (ISSN) Movahedi, S ; Adeli, M ; Fard, A. K ; Maleki, M ; Sadeghizadeh, M ; Bani, F ; Sharif University of Technology
    2013
    Abstract
    This work presents a procedure for functionalization of graphene sheets from edges by polyglycerol. Hyperbranched polyglycerol with a bi-dentate aromatic segment in its focal point was synthesized and used to sandwich graphene sheets from the cut-edges. Due to the hydrophobicity of the flat surface of the edge-functionalized graphenes and hydrophilicity of their edges, they changed their conformation from the extended- to the closed-state and formed nanocapsules in aqueous solutions. Spectroscopy and microscopy evaluations showed that the average size for nanocapsules is 300 nm. They were able to encapsulate hydrophobic molecules such as doxorubicin in aqueous solutions with a high loading... 

    Temperature-responsive smart nanocarriers for delivery of therapeutic agents: applications and recent advances

    , Article ACS Applied Materials and Interfaces ; Volume 8, Issue 33 , 2016 , Pages 21107-21133 ; 19448244 (ISSN) Karimi, M ; Sahandi Zangabad, P ; Ghasemi, A ; Amiri, M ; Bahrami, M ; Malekzad, H ; Ghahramanzadeh Asl, H ; Mahdieh, Z ; Bozorgomid, M ; Ghasemi, A ; Rahmani Taji Boyuk, M. R ; Hamblin, M. R ; Sharif University of Technology
    American Chemical Society  2016
    Abstract
    Smart drug delivery systems (DDSs) have attracted the attention of many scientists, as carriers that can be stimulated by changes in environmental parameters such as temperature, pH, light, electromagnetic fields, mechanical forces, etc. These smart nanocarriers can release their cargo on demand when their target is reached and the stimulus is applied. Using the techniques of nanotechnology, these nanocarriers can be tailored to be target-specific, and exhibit delayed or controlled release of drugs. Temperature-responsive nanocarriers are one of most important groups of smart nanoparticles (NPs) that have been investigated during the past decades. Temperature can either act as an external... 

    Hydrazine-modified starch coated magnetic nanoparticles as an effective pH-responsive nanocarrier for doxorubicin delivery

    , Article Journal of Industrial and Engineering Chemistry ; Volume 39 , 2016 , Pages 203-209 ; 1226086X (ISSN) Zohreh, N ; Hosseini, S. H ; Pourjavadi, A ; Sharif University of Technology
    Korean Society of Industrial Engineering Chemistry  2016
    Abstract
    A novel, magnetic nanocarrier was successfully synthesized through a facile and economical producer in which Fe3O4 magnetic nanoparticles were coated by starch-g-poly (methyl methacrylate-co-PEG-acrylamide). The surface of nanocarrier was then modified by hydrazine to preparation of a pH-responsive carrier. The resulted nanocarrier was applied for delivery of doxorubicin (DOX) as an effective anti-cancer drug. DOX was reacted with hydrazine linkage on the surface of nanocarrier to form hydrazone bond. Due to the presence of numerous hydrazine groups on the surface of magnetic nanocarrier large amounts of DOX was loaded onto the carrier (327 mg g−1). © 2016 The Korean Society of Industrial... 

    Functionalized mesoporous silica-coated magnetic graphene oxide by polyglycerol-g-polycaprolactone with pH-responsive behavior: designed for targeted and controlled doxorubicin delivery

    , Article Journal of Industrial and Engineering Chemistry ; 2015 ; ISSN: 1226086X Pourjavadi, A ; Tehrani, Z. M ; Jokar, S ; Sharif University of Technology
    Abstract
    In the present work a novel multifunctional drug nanocarrier was prepared. Polyglycerol-. g-polycaprolactone was grafted on Mesoporous silica-coated magnetic graphene oxide. Doxorubicin, as anticancer drug, was loaded on this carrier. The in vitro drug release showed the controlled pH responsive behavior. At the endosomal pH (pH 5.5) the amount of drug release enhanced. This nanocarrier would have potential application in the tumor therapy owing to its biodegradability, controlled release and pH responsive behavior  

    Synthesis of Graphene Aerogel for Potential Application in Drug Delivery

    , M.Sc. Thesis Sharif University of Technology Ayazi, Hossein (Author) ; Akhavan, Omid (Supervisor) ; Raufi, Mohammad (Supervisor)
    Abstract
    Since the development of various anti-cancer drugs, numerous attempts have been made to decrease their off-target adverse effects anhance their efficiency.Among these efforts developing novel drug delivery systems have been demonstrate promising potentials and lots of carriers have reached the market and clinical phases.Although plentiful researches on different drug carriers, lots of problems in drug loading, release and final efficiency are yet remaind.In recent decade, graphene oxide and graphene aerogel have been attracted remarkable intrest as drug carriers, due to their biodegradable and biocompatible characteristics.Accordingly, in this study graphene aerogel have been synthesized... 

    Synthesis of Magnetic Nanocarriers Based on Coating of Fe3O4 with Modified Biodegradable Polysaccharides by pH Sensitive Agents for Targeted Release of Anticancer Drug Doxorubicin

    , M.Sc. Thesis Sharif University of Technology Amin, Shiva Sadat (Author) ; Pourjavadi, Ali (Supervisor)
    Abstract
    One of the major problems in cancer treatment is the side effects of the drugs. Nowadays, scientists are developing smart nanocarriers which used for diagnosis and delivering drugs in order to circulate through blood vessels, pass the immune system, attach to cancer cells and kill them without any side effects. In the first research of this thesis, magnetic nanoparticles were coated by modified alginate and used as smart nanocarriers. Magnetic nanocarrier were sysnthesized based on hydrophobic coating of oleic acid and hydrazine oleate-modified alginate shell. The resulting carrier is pH-sensitive and the alginate shell removes in the low pH medium. DOX was placed between hydrophobic chains.... 

    Synthesis of Molecularly Imprinted Nano-porous Polymer for the Enrichment of Taxol as Anti-Cancer Agent

    , M.Sc. Thesis Sharif University of Technology Shirzaei Sani, Ehsan (Author) ; Abdekhodaie, Mohammad Jafar (Supervisor) ; Nematollahzadeh, Ali (Co-Advisor) ; Musavi, Abbas (Co-Advisor)
    Abstract
    In the present research, first, a series of molecular dynamics (MD) simulations of pre-polymerization mixtures for taxol (template) imprinted polymers was performed to select an appropriate monomer and its intermolecular bonds with the template. Finally, after synthesis, performance and morphological evaluation of taxol imprinted polymer were presented. In the molecular modeling step, a virtual library of functional monomers was created containing eleven frequently used monomers. The MD simulations were first conducted to select the optimum monomer from the virtual library using acetonitrile as porogen. Methacrylic acid among the studied functional monomers was found to possess stronger... 

    Loading of Doxorubicin on Stimuli-Responsive Nanocarriers and Investigation of its Release

    , M.Sc. Thesis Sharif University of Technology Yaghoubi, Mahshid (Author) ; Pourjavadi, Ali (Supervisor)
    Abstract
    Drug targeting to specific organs and tissues has become one of the critical endeavors of the new century. Magnetic nanoparticles have gained a lot of attention in biomedical and industrial application. Doxorubicin is an effective anti-cancer drug in the treatment of many types of cancers. The aim of this study is to load doxorubicin on stimuli-responsive nanocarriers. These nanocarriers are prepared from magnetic nanoparticles. Then these magnetic nanparticles are coated by copolymer of poly(glycidyl methacrylate) then reacted with hydrazine and hydrazide functional group is formed that can chemically be bonded with the anticancer drug doxorubicin via a hydrazone bond formation. This... 

    Multi-scale Simulation of Tumor Microenvironment

    , M.Sc. Thesis Sharif University of Technology Nikmaneshi, Mohammad Reza (Author) ; Firoozabadi, Bahar (Supervisor) ; Mozafari, Ali Asghar (Co-Supervisor)
    Abstract
    Search for effective methods for treating cancer requires a deep understanding of the tumor microenvironment and its role in cancerous tumor growth and progression. Mathematical modeling methods, which have fewer limitations than experimental methods for examining the microcirculation of cancer in detail, are suggested to answer many questions about the behavior and dynamics of cancerous tumors. In the present study, a multi-scale mathematical model of the three-dimensional tumor microenvironment, including molecular, cellular, and tissue scales, is presented. In this model, important aspects of tumor microenvironmental dynamics including tumor growth, angiogenesis, cancer metabolism, and... 

    Design a New Sugar- amino Acid-based Drug Structure as an Alternative to Methotrexate, with the Aim of Treating Leukemia and some Autoimmune Diseases

    , M.Sc. Thesis Sharif University of Technology Shapouri, Amin Mohammad (Author) ; Fattahi, Alireza (Supervisor)
    Abstract
    This project aims to design a drug to fight leukemia and some autoimmune diseases having few side effects. These drugs are composed of natural sugar and amino acid structures. Among the various treatments available, drug structures as inhibitors of enzymes involved in cancer-related cellular processes is an important treatment. Methotrexate is one of the most widely used anticancer drugs in the last half-century and treats leukemia and many autoimmune diseases such as psoriasis. It is a derivative of folic acid (vitamin B9) and one of the drugs with specific properties. It is an anti-folate whose anti-metabolic effects can help kill cancer cells. One of the problems with using this drug to...