Sharif Digital Repository

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... 

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... 

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... 

Today, current methods are used for treatment of cancers. Patient experiences a period of hard treatment during destruction of both healthy and diseased cells. Researchers are following stimulus- response drug delivery systems that they control time and position of drug release. Meanwhile, micellar nanoparticles are important, because it can transport the hydrophobic anticancer drugs from body's physiological barriers. On the other hand, tumour tissue has low pH and high temperature as compared to health tissue. Therefore, using pH and thermosensitive polymer coating could be effective in triggered drug release. In the first study, micellar systems were synthesized which were responsive to... 

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.... 

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... 

The use of nanocarriers has been recently considered for targeted drug delivery. In the targeted drug delivery systems, drug is directed to the target tissue and its adverse effects are reduced on the healthy tissues. Graphene oxide and hollow mesoporous carbon nanospheres are two types of the most interesting carbon-based nanocarriers because of their unique properties. Aim of the thesis has been the synthesis of the nanocarriers based-on graphene oxide and hollow mesoporous carbon nanospheres and their surface modifications by magnetic polyamidoamine dendrimer and oxygen-rich polymers such as poly(epichlorohydrin) and hyperbranched polyglycerol. These modifications result in higher... 

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... 

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... 

1- Mesoporous silica materials have been found to possess pore sizes ranging from 2 -10 nm alongside 2D-hexagonal and 3D-cubic structural features. The specific properties of nanoparticles of the mesoporous silica family, such as the collected size, porosity, morphology, and high chemical stability, make them among the best drug delivery systems and catalysts. Designing the catalysts with advanced structures that effectively locate the transition metals and create active centres onto the surfaces of mesoporous silica materials has attracted extraordinary attention. According to many studies, mesoporous silica materials without organic functional groups cannot be used as catalysts in chemical... 

Nowadays, advanced and inexpensive pre-clinical methods for investigating the effects of anti-cancer drugs are expanding. One of the latest three-dimensional laboratory modeling for evaluating the effects of drugs is the use of tumor-on-chip technology, which actually models the physiological system of the body through three-dimensional scaffolds, multicellular cultures, and shaped vascular systems. In this study, three-dimensional culture of cancer cells was performed in the form of spheroids. A chip of U-shaped microstructures with and without gaps was used to trap cells and form cancer spheroids. We simulated the simultaneous effect of drug and oxygen concentration distribution inside the... 

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... 

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... 

One of the goals of the current research is to investigate natural structures to inhibit Ras proteins that belong to the family of guanosine triphosphatase proteins. For example, one of the common mutations is Kras mutations, which are seen exclusively in pancreatic ductal adenocarcinoma. Changes in Kras protein expression are observed in 30 percent of lung cancer cases. Kras mutations occur in 35-45 percent of colon cancers, leading to drug resistance. Our work method in this research is that we collect a dataset of natural compounds for the target protein. Then, the binding energies of these structures with the receptor protein are calculated through Autodoc Vina. After that, using deep... 

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  

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... 

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... 

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...