Sharif Digital Repository

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,... 

Free-energy calculations are crucial for investigating biomolecular interactions. However, in theoretical studies, the neglect of electronic polarization can reduce predictive capabilities, specifically for free-energy calculations. To effectively mimick polarization, we explore a Charge Switching (CS) model, aiming to narrow the gap between computational and experimental results. The model requires quantum-level partial charge calculations of the molecule in different environments, combined with atomistic MD simulations. Studying three different anti-cancer drug molecules with three different phospholipid membranes, we show that the method significantly improves agreement with available... 

PIM-1 is a serine-threonine kinase mainly expressed in tissues like the Thymus, spleen, bone marrow, and liver. Overexpression of PIM kinases occurs in various types of human tumours, such as lymphomas, prostate cancer, and oral cancer. As a result, the design of drugs to inhibit PIM-1 in cancerous cells has attracted much attention in recent years. This study aimed to design the alternative inhibitors for PIM-1 kinase, which are based on carbohydrates and amino acids and are expected to be non-toxic with the same chemotherapeutic effects as the traditional known anticancer drugs. The combinatorial use of quantum mechanics (QM) and molecular dynamic simulation (MD) has enabled us to... 

In this study, a folic acid-functionalized niosome was formulated and loaded with letrozole and curcumin as a promising drug carrier system for chemotherapy of the breast cancer cells. The formulation process was optimized by varying the type of Span 80 and total lipid to drug ratio, where Span 80 and lipid to drug molar ratio of 10 resulted in the niosomes with maximum encapsulation of both drugs but minimum size. The developed niosomal formulation showed a great storage stability up to one month with the small changes in drug encapsulation efficiency and size during the storage. In addition, they showed a pH-dependent release behaviour with slow drug release at physiological pH (7.4) while... 

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... 

Since most of the anticancer drugs have low solubility in water, the clinical use of them is limited unless by some modification the solubility increases or the drug is carried with a soluble compartment. To solve this problem, we prepared a magnetic nanocarrier with a hydrophobic surface based on oleic acid chains in which hydrophobic drug molecules such as doxorubicin hydrochloride (DOX) and paclitaxel (PTX) are easily adsorbed onto the surface. Since the drug molecules are physically adsorbed on the surface, large amounts of DOX (282 mg·g-1) and PTX (316 mg·g-1) were immobilized onto the nanocarrier. Then, the surface of the drug loaded magnetic core was covered by a smart pH-sensitive... 

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... 

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... 

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... 

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... 

This work focused on the design of new pH-responsive nanoparticles for controlled delivery of anticancer drug doxorubicin (Dox). Nanoparticles of poly(methacrylic acid)-polysorbate 80-grafted starch (PMAA-PS 80-g-St) were synthesized by using a one-pot method that enabled simultaneous grafting of PMAA and PS 80 onto starch and nanoparticle formation in an aqueous medium. The particles were characterized by FTIR, 1H NMR, TEM, DLS, and potentiometric titration. Dox loading and in vitro release from the nanoparticles were investigated. The FTIR and 1H NMR confirmed the chemical composition of the graft terpolymer. The nanoparticles were relatively spherical with narrow size distribution and... 

N,N′,N″-triethylenethiophosphoramide (Thiotepa) and its oxo analogue (Tepa) as the major metabolite are trifunctional alkylating agents with a broad spectrum of antitumor activity. In vivo and vitro studies show alkylation of DNA by Thiotepa and Tepa can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. In pathway 1, these agents are capable of forming cross-links with DNA molecules via two different mechanisms. In the first mechanism, the ring opening reaction is initiated by protonating the aziridine, which then becomes the primary target of nucleophilic attack by the N7-Guanine. The second one is a direct nucleophilic ring opening of... 

Since there have been many difficulties in clinical administration of anticancer drugs due to their poor solubility & targeting, development of new biodegradable Nano-carriers can provide good solutions to overcome the most of recent problems to obtain a better controlled release and targeted delivery of drugs with better efficiency and less side-effects. Acidic pH is regarded as a phenotypic characteristic of cancer tumors. Under this acidic condition, it is known that the surface charge of Chitosan-modified nano-particles become more positive. On the other hand, cancer cells are negatively charged. It is worth mentioning that by loading of anticancer drugs into this novel system, a strong... 

Superparamagnetic iron oxide nanoparticles with proper surface coatings are increasingly being evaluated for clinical applications such as hyperthermia, drug delivery, magnetic resonance imaging, transfection, and cell/protein separation. To enhance the applicability of magnetic nanoparticles, two main problems must be overcome. First, as the drug coats the particle surface, a significant portion of it is quickly released upon injection (burst effect). Therefore, only small amounts of the drug reach the specific site after, for example, magnetic drug targeting. Second, once the surface-derivatized nanoparticles are inside the cells, the coating is likely digested, leaving the bare particles...