Sharif Digital Repository

DNA polymerase η (polη) is of significant value for designing new families of anticancer drugs. This protein takes a role in many stages of the cell cycle, including DNA replication, translesion DNA synthesis, and the repairing process of DNA. According to many studies, a high level of expression of polη in most cases has been associated with low rates of patients' survival, regardless of considering the stage of tumor cells. Thus, the design of new drugs with fewer side effects to inhibit polη in cancerous cells has attracted attention in recent years. This project aims to design and explore the alternative inhibitors for polη, which are based on carbohydrates and amino acids. In terms of... 

Despite the great potential of carbon nanotubes (CNTs) in various areas of biomedicine, concerns regarding their carcinogenicity, inefficient dispersion in aqueous solutions and biological activity in vivo still remain. One important and feasible route to overcome these barriers is modification of CNTs with polymers, which are widely studied and play a vital role in biological and biomedical fields, especially in drug delivery. This comprehensive review focuses on the achievements of our and other groups in currently used methods to functionalize the surface of CNTs with polymers to produce anticancer drug delivery systems. We have intensively studied covalent and noncovalent interactions... 

During the drug delivery process in chemotherapy, both of the cancer cells and normal healthy cells may be killed. In this paper, three mathematical cell-kill models including log-kill hypothesis, Norton-Simon hypothesis and Emax hypothesis are considered. Three control approaches including optimal linear regulation, nonlinear optimal control based on variation of extremals and H∞-robust control based on μ-synthesis are developed. An appropriate cost function is defined such that the amount of required drug is minimized while the tumor volume is reduced. For the first time, performance of the system is investigated and compared for three control strategies; applied on three nonlinear models... 

Tumor microenvironment (TME) is a multi-scale biological environment that can control tumor dynamics with many biomechanical and biochemical factors. Investigating the physiology of TME with a heterogeneous structure and abnormal functions not only can achieve a deeper understanding of tumor behavior but also can help develop more efficient anti-cancer strategies. In this work, we develop a hybrid multi-scale mathematical model of TME to simulate the progression of a three-dimensional tumor and elucidate its response to different chemotherapy approaches. The chemotherapy approaches include multiple low dose (MLD) of anti-cancer drug, maximum tolerated dose (MTD) of anti-cancer drug,... 

A total of 6289 drug-like anticancer molecules were collected from Binding database and were analyzed by using the classification techniques. The collected molecules were encoded to a diverse set of descriptors, spanning different physical and chemical properties of the molecules. A combination of genetic algorithms and counterpropagation artificial neural networks was used for navigating the generated drug-like chemical space and selecting the most relevant molecular descriptors. The proposed method was used for the classification of the molecules according to their therapeutic targets and activities. The selected molecular descriptors in this work define discrete areas in chemical space,... 

In the present study, the potential of doxorubicin hydrochloride (DOX)-loaded electrospun chitosan/cobalt ferrite/titanium oxide nanofibers was studied to investigate the simultaneous effect of hyperthermia and chemotherapy against melanoma cancer B16F10 cell lines. The cobalt ferrite nanoparticles were synthesized via microwave heating method. The titanium oxide nanoparticles were mixed with cobalt ferrite to control the temperature rise. The synthesized nanoparticles and nanofibers were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and vibrating sample magnetometer (VSM) analysis. The DOX loading efficiency and in vitro drug release of... 

Free polymer graphene aerogel nanoparticles (GA NPs) were synthesized by using reduction/aggregation of graphene oxide (GO) sheets in the presence of vitamin C (as a biocompatible reductant agent) at a low temperature (40 °C), followed by an effective sonication. Synthesis of GA NPs in doxorubicin hydrochloride (DOX)-containing solution results in the simultaneous synthesis and drug loading with higher performance (than that of the separately synthesized and loaded samples). To investigate the mechanism of loading and the capability of GA NPs in the loading of other drug structures, two groups of ionized (DOX, Amikacin sulfate and, D-glucosamine hydrochloride) and non-ionized (Paclitaxel... 

The coaxial electrospinning for producing core-shell nanofibers due to control the release profile of drug by the shell layer has been developed. N-carboxymethyl chitosan (CMC)-polyvinyl alcohol (core)/poly(ε-caprolactone) (PCL) (shell) nanofibers were produced via coaxial electrospinning. Doxorubicin (DOX) and nickel ferrite nanoparticles were incorporated into the nanofibers for controlled release of DOX against MCF-7 breast cancer. The minimum CMC/PCL fiber diameter was found to be 300 nm by optimizing of three variables including voltage to distance ratio (1.5–2.5 kV/cm), CMC concentration (4−6 wt.%) and PCL concentration (8−12 wt.%). The synthesized core-shell fibers were characterized... 

The coaxial electrospinning for producing core-shell nanofibers due to control the release profile of drug by the shell layer has been developed. N-carboxymethyl chitosan (CMC)-polyvinyl alcohol (core)/poly(ε-caprolactone) (PCL) (shell) nanofibers were produced via coaxial electrospinning. Doxorubicin (DOX) and nickel ferrite nanoparticles were incorporated into the nanofibers for controlled release of DOX against MCF-7 breast cancer. The minimum CMC/PCL fiber diameter was found to be 300 nm by optimizing of three variables including voltage to distance ratio (1.5–2.5 kV/cm), CMC concentration (4−6 wt.%) and PCL concentration (8−12 wt.%). The synthesized core-shell fibers were characterized... 

In the current study, the physicochemical and biological properties of tetracycline-loaded core-shell nanoparticles (Tet/Ni0.5Co0.5Fe2O4/SiO2 and Tet/CoFe2O4/SiO2) were investigated. The antibacterial activity of nanoparticles alone and in combination with tetracycline was investigated against a number of Gram-positive and Gram-negative bacteria for determining minimum inhibitory concentration (MIC) values. The MIC of Tet/Ni0.5Co0.5Fe2O4/SiO2 nanoparticles turned out to be significantly higher than that of Tet/CoFe2O4/SiO2 nanoparticles. Furthermore, Tet/Ni0.5Co0.5Fe2O4/SiO2 nanoparticles exhibited potent antibiofilm activity against pathogenic bacteria compared to Tet/CoFe2O4/SiO2... 

Introduction: Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis.Areas covered: Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal compound amphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations)... 

Introduction - Recently, there have been growing attention on the modification and optimisation of new extraction and quantification methods, caused by the lack of environmentally friendly methodologies for the extraction of phytochemicals from complex matrices. In the case of pharmaceutical compounds, not only the extraction procedure but also the analysis method should be efficient, precise, fast and easy.Objectives - The essential pharmaceutical characteristics and trace concentration of withanolides led us to modify and optimise the previously reported extraction and quantification procedure for withaferin A (WA) as a candidate for withanolides.Matrial and methods - The WA from the... 

Breast and prostate cancers are common types of cancers with various strategies, such as chemotherapy and radiotherapy, for their therapy. Since these methods have undesired side effects and poor target affinity, neoteric strategies—known as aptamer-based smart drug delivery systems (SDDSs)—have been developed in recent years to overcome the obstacles of current treatment, and investigated for a clinical trial. The high affinity and versatility of aptamers for binding to the corresponding targets make them highly noticeable agents in the drug delivery domains. In addition to their exceptional benefits, aptamers are able to overcome tumor resistance because of their high selectivity and low... 

We report the development of a metastasis-on-a-chip platform to model and track hepatocellular carcinoma (HCC)–bone metastasis and to analyze the inhibitory effect of an herb-based compound, thymoquinone (TQ), in hindering the migration of liver cancer cells into the bone compartment. The bioreactor consisted of two chambers, one accommodating encapsulated HepG2 cells and one bone-mimetic niche containing hydroxyapatite (HAp). Above these chambers, a microporous membrane was placed to resemble the vascular barrier, where medium was circulated over the membrane. It was observed that the liver cancer cells proliferated inside the tumor microtissue and disseminated from the HCC chamber to the... 

Exploring efficient chemotherapy would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. As in vivo experimental methods are unable to isolate or control individual factors of the TME, and in vitro models often cannot include all the contributing factors, some questions are best addressed with mathematical models of systems biology. In this study, we establish a multi-scale mathematical model of the TME to simulate three-dimensional tumor growth and angiogenesis and then implement the model for an array of chemotherapy approaches to elucidate the effect of TME conditions and drug scheduling on controlling tumor progression. The... 

Introduction: To date, numerous iron-based nanostructures have been designed for cancer therapy applications. Although some of them were promising for clinical applications, few efforts have been made to maximize the therapeutic index of these carriers. Herein, PEGylated silica-coated iron oxide nanoparticles (PS-IONs) were introduced as multipurpose stimuli-responsive co-delivery nanocarriers for a combination of dual-drug chemotherapy and photothermal therapy. Methods: Superparamagnetic iron oxide nanoparticles were synthesized via the sonochemical method and coated by a thin layer of silica. The nanostructures were then further modified with a layer of di-carboxylate polyethylene glycol... 

Introduction: To date, numerous iron-based nanostructures have been designed for cancer therapy applications. Although some of them were promising for clinical applications, few efforts have been made to maximize the therapeutic index of these carriers. Herein, PEGylated silica-coated iron oxide nanoparticles (PS-IONs) were introduced as multipurpose stimuli-responsive co-delivery nanocarriers for a combination of dual-drug chemotherapy and photothermal therapy. Methods: Superparamagnetic iron oxide nanoparticles were synthesized via the sonochemical method and coated by a thin layer of silica. The nanostructures were then further modified with a layer of di-carboxylate polyethylene glycol... 

A novel magnetic nanocarrier with long spacer length and high colloidal stability has been prepared for effective delivery of doxorubicin (DOX). First, poly(amidoamine) (PAMAM) dendrimer was grown up onto the surface of superparamagnetic iron oxide nanoparticles to increase the loading amount of amine groups. Then, terminal amine groups were functionalized by polyethylene glycol dimethylester to increase the spacer length. Then anticancer drug DOX was covalently attached onto the system by hydrazone bond to forms a pH-sensitive nanocarrier. This system is designed to combine the advantage of magnetic targeting, high drug loading capacity, and controlled release  

Phytochemical investigation of the aerial parts of Salvia eremophila led to the isolation of a lupane triterpenoid, 3β, 20-dihydroxylupane-28-oic acid (1), together with eight other compounds, comprising three diterpene, two triterpene, two flavonoids and a steroidal glucoside. Their structures were elucidated by interpretation of their one-dimensional and two-dimensional NMR spectra and completed by the analysis of the HRESIMS data. Compounds 1, 2-4 and 8 were evaluated for their cytotoxicities against five human tumour cell lines. Compounds 1 and 3 hold a good potential for use in future studies due to their anti-cancer properties