Publications by authors named "Hamed Nosrati"

34 Publications

Nanotechnology against the novel coronavirus (severe acute respiratory syndrome coronavirus 2): diagnosis, treatment, therapy and future perspectives.

Nanomedicine (Lond) 2021 03 8;16(6):497-516. Epub 2021 Mar 8.

Department of Public Health Sciences, University of Miami, Miami, FL 33146, USA.

COVID-19, as an emerging infectious disease, has caused significant mortality and morbidity along with socioeconomic impact. No effective treatment or vaccine has been approved yet for this pandemic disease. Cutting-edge tools, especially nanotechnology, should be strongly considered to tackle this virus. This review aims to propose several strategies to design and fabricate effective diagnostic and therapeutic agents against COVID-19 by the aid of nanotechnology. Polymeric, inorganic self-assembling materials and peptide-based nanoparticles are promising tools for battling COVID-19 as well as its rapid diagnosis. This review summarizes all of the exciting advances nanomaterials are making toward COVID-19 prevention, diagnosis and therapy.
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http://dx.doi.org/10.2217/nnm-2020-0441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938776PMC
March 2021

CRISPR Systems for COVID-19 Diagnosis.

ACS Sens 2021 Jan 27. Epub 2021 Jan 27.

NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.

The emergence of the new coronavirus 2019 (COVID-19) was first seen in December 2019, which has spread rapidly and become a global pandemic. The number of cases of COVID-19 and its associated mortality have raised serious concerns worldwide. Early diagnosis of viral infection undoubtedly allows rapid intervention, disease management, and substantial control of the rapid spread of the disease. Currently, the standard approach for COVID-19 diagnosis globally is the RT-qPCR test; however, the limited access to kits and associated reagents, the need for specialized lab equipment, and the need for highly skilled personnel has led to a detection slowdown. Recently, the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic systems has reshaped molecular diagnosis. The benefits of the CRISPR system such as speed, precision, specificity, strength, efficiency, and versatility have inspired researchers to develop CRISPR-based diagnostic and therapeutic methods. With the global COVID-19 outbreak, different groups have begun to design and develop diagnostic and therapeutic programs based on the efficient CRISPR system. CRISPR-based COVID-19 diagnostic systems have advantages such as a high detection speed (i.e., 30 min from raw sample to reach a result), high sensitivity and precision, portability, and no need for specialized laboratory equipment. Here, we review contemporary studies on the detection of COVID-19 based on the CRISPR system.
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http://dx.doi.org/10.1021/acssensors.0c02312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860143PMC
January 2021

Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis.

J Nanobiotechnology 2021 Jan 4;19(1). Epub 2021 Jan 4.

Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Skin is the body's first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.
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http://dx.doi.org/10.1186/s12951-020-00755-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784275PMC
January 2021

Stem cell-based therapeutic strategies for corneal epithelium regeneration.

Tissue Cell 2021 Feb 19;68:101470. Epub 2020 Nov 19.

Department of Materials Science and Engineering, Golpayegan University of Technology, Golpayegan, Iran.

Any significant loss of vision or blindness caused by corneal damages is referred to as corneal blindness. Corneal blindness is the fourth most common cause of blindness worldwide, representing more than 5% of the total blind population. Currently, corneal transplantation is used to treat many corneal diseases. In some cases, implantation of artificial cornea (keratoprosthesis) is suggested after a patient has had a donor corneal transplant failure. The shortage of donors and the side effects of keratoprosthesis are limiting these approaches. Recently, researchers have been actively pursuing new approaches for corneal regeneration because of these limitations. Nowadays, tissue engineering of different corneal layers (epithelium, stroma, endothelium, or full thickness tissue) is a promising approach that has attracted a great deal of interest from researchers and focuses on regenerative strategies using different cell sources and biomaterials. Various sources of corneal and non-corneal stem cells have shown significant advantages for corneal epithelium regeneration applications. Pluripotent stem cells (embryonic stem cells and iPS cells), epithelial stem cells (derived from oral mucus, amniotic membrane, epidermis and hair follicle), mesenchymal stem cells (bone marrow, adipose-derived, amniotic membrane, placenta, umbilical cord), and neural crest origin stem cells (dental pulp stem cells) are the most promising sources in this regard. These cells could also be used in combination with natural or synthetic scaffolds to improve the efficacy of the therapeutic approach. As the ocular surface is exposed to external damage, the number of studies on regeneration of the corneal epithelium is rising. In this paper, we reviewed the stem cell-based strategies for corneal epithelium regeneration.
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http://dx.doi.org/10.1016/j.tice.2020.101470DOI Listing
February 2021

Biopolymer-based scaffolds for corneal stromal regeneration: A review.

Polim Med 2020 Jul-Dec;50(2):57-64

Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

The stroma is one of the 5 layers of the cornea that comprises more than 90% of the corneal thickness, and is the most important layer for the transparency of cornea and refractive function critical for vision. Any significant damage to this layer may lead to corneal blindness. Corneal blindness refers to loss of vision or blindness caused by corneal diseases or damage, which is the 4th most common cause of blindness worldwide. Different approaches are used to treat these patients. Severe corneal damage is traditionally treated by transplantation of a donor cornea or implantation of an artificial cornea. Other alternative approaches, such as cell/stem cell therapy, drug/gene delivery and tissue engineering, are currently promising in the regeneration of damaged cornea. The aim of tissue engineering is to functionally repair and regenerate damaged cornea using scaffolds with or without cells and growth factors. Among the different types of scaffolds, polymer-based scaffolds have shown great potential for corneal stromal regeneration. In this paper, the most recent findings of corneal stromal tissue engineering are reviewed.
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http://dx.doi.org/10.17219/pim/127653DOI Listing
December 2020

Corneal epithelium tissue engineering: recent advances in regeneration and replacement of corneal surface.

Regen Med 2020 08 10;15(8):2029-2044. Epub 2020 Nov 10.

Department of Tissue Engineering & Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Currently, many corneal diseases are treated by corneal transplantation, artificial corneal implantation or, in severe cases, keratoprosthesis. Owing to the shortage of cornea donors and the risks involved with artificial corneal implants, such as infection transmission, researchers continually seek new approaches for corneal regeneration. Corneal tissue engineering is a promising approach that has attracted much attention from researchers and is focused on regenerative strategies using various biomaterials in combination with different cell types. These constructs should have the ability to mimic the native tissue microenvironment and present suitable optical, mechanical and biological properties. In this article, we review studies that have focused on the current clinical techniques for corneal replacement. We also describe tissue-engineering and cell-based approaches for corneal regeneration.
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http://dx.doi.org/10.2217/rme-2019-0055DOI Listing
August 2020

Preparation and characterization of poly(ethylene oxide)/zinc oxide nanofibrous scaffold for chronic wound healing applications.

Polim Med 2020 Jan-Jun;50(1):41-51

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background: Skin, the first barrier to pathogens, loses its integrity and function after an injury. The presence of an antibacterial dressing at the wound site may prevent bacterial invasion and also improve the healing process.

Objectives: The current study aimed to fabricate a biomimetic membrane with antibacterial properties for healing chronic wounds.

Material And Methods: The membranes, fabricated through electrospinning, are comprised of poly(ethylene oxide) (PEO) and zinc oxide nanoparticles (ZnO-NPs) as the main biomaterial and antibacterial agent, respectively. Antibacterial activity, cell attachment and viability were tested to evaluate the biological properties of the membranes. The optimal cell compatible concentration of ZnO-NPs was determined for further studies. In vitro characterization of the membranes was performed to confirm their suitable properties for wound healing.

Results: The antibacterial PEO/ZnO-NP membrane containing 2% of nanoparticles showed no cell toxicity, and human fibroblast cells were able to adhere and proliferate on the scaffold. The in vitro results from the tensile test, wettability, porosity, and protein adsorption revealed appropriate properties of the membrane as a scaffold for skin tissue engineering.

Conclusions: Synthetic polymers have been widely used for tissue engineering applications. The proper characteristics of PEO nanofibers, including a high ratio of surface/volume, moderate hydrophilicity and good mechanical properties, make this polymer interesting for skin regeneration. The results demonstrate the potential of the antibacterial PEO/ZnO-NP membrane to be used as an engineered scaffold to improve the wound healing process.
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http://dx.doi.org/10.17219/pim/128378DOI Listing
November 2020

Improved synergic therapeutic effects of chemoradiation therapy with the aid of a co-drug-loaded nano-radiosensitizer under conventional-dose X-ray irradiation.

Biomater Sci 2020 Aug 26;8(15):4275-4286. Epub 2020 Jun 26.

Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

The goal of this work is to harness the advantages of a targeted hybrid nanostructure, BSA-coated FeO (F)-Au heterodimer, as a radiosensitizer and co-delivery vehicle of chemotherapeutic drugs for enhanced synergic cancer therapy and protection of healthy tissues. F-Au-BSA-MTX-CUR combines the abilities of enhanced X-ray radiation therapy (F-Au), long blood circulation time (BSA), tumor targeting (MTX), enhanced chemotherapy (MTX and CUR), and protection of normal cells against the harmful effects of radiation (CUR). In this work, we present the radioprotective and radiosensitizing effects of CUR on normal tissues and the tumor site, respectively. After technical evaluation, drug loading, drug release behavior, hemolysis assay, transfection efficacy, and cellular uptake studies with fluorescence microscopy, the biosafety and toxicity of the nanostructure was assessed in vitro and in vivo. Also, to confirm its power to improve synergistic chemoradiation therapy in mice, the antitumor effects of the designed treatment plan were assessed in a 4T1-tumor bearing mouse model. The in vivo antitumor effect evaluation interestingly reveals outstanding therapeutic power of the final formulation (F-Au-BSA-MTX-CUR) and further requirement of CUR as a radioprotective. This result importantly revealed the radioprotection effect of CUR. Co-delivery of the chemotherapeutic drugs MTX and CUR, combined with the radiosensitizing effect of the F-Au heterodimer and the radioprotective effect of CUR, showed promising prospects in cancer therapy.
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http://dx.doi.org/10.1039/d0bm00353kDOI Listing
August 2020

Vancomycin-loaded electrospun polycaprolactone/nano-hydroxyapatite membrane for the treatment of blood infections.

Med Hypotheses 2020 Nov 12;144:109992. Epub 2020 Jun 12.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Nowadays, because of the resistance of bacteria to antibiotics, researchers are trying to make new antibiotics or sometimes even bring them back into the treatment cycle so that they could eliminate the bacteria's resistance. On the other hand, the use of nanofibers has become widespread in many fields for their unique properties and convenient design. The present study focuses on the production of hydrophobic nanofibers to absorb the bacteria and their toxins from the bloodstream that contains the infection. Many bacterial surfaces have hydrophobic surfactant properties due to hydrophobic surface protein. According to the principle of binding two hydrophobic molecules to each other in an aqueous medium, the nanofibers are designed to physically absorb the bacteria. The use of antibiotics in the study can remove some unattached bacteria. In addition, using nanofiber manufacturing techniques can reduce the resistance of bacteria to antibiotics. The construction of the desired membrane can be used in subsequent studies as a replacement membrane for dialysis filters.
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http://dx.doi.org/10.1016/j.mehy.2020.109992DOI Listing
November 2020

Physical and biological properties of blend-electrospun polycaprolactone/chitosan-based wound dressings loaded with N-decyl-N, N-dimethyl-1-decanaminium chloride: An in vitro and in vivo study.

J Biomed Mater Res B Appl Biomater 2020 11 27;108(8):3084-3098. Epub 2020 May 27.

Department of Tissue Engineering and Biomaterials, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran.

Dual-pump electrospinning of antibacterial N-decyl-N, N-dimethyl-1-decanaminium-chloride (DDAC)-loaded polycaprolactone (PCL) nanofibers, and chitosan (CS)/polyethylene-oxide (PEO)-based wound dressings with hydrophilic and hydrophobic properties to eliminate and absorb pathogenic bacteria from wound surface besides antibacterial action and to support wound healing and accelerate its process. Physicochemical properties of the prepared nanofibrous mat as well as antibacterial, cytotoxicity, and cell compatibility were studied. The full-thickness excisional wound healing properties up to 3 weeks using hematoxylin and eosin and Masson-trichrome staining were investigated. Addition of DDAC to CS/PEO-PCL mats decreased the diameter of the nanofibers, which is a crucial property for wound healing as large surface area per volume ratio of nanofibers, in addition to proper cell adhesion, increases loading of DDAC in mats and leads to increased cell viability and eliminating Gram-positive bacteria at in vitro studies. In vivo studies showed DDAC-loaded CS/PEO-PCL mats increased epithelialization and angiogenesis and decreased the inflammation according to histological results. We demonstrated that hydrophobic PCL/DDAC mats, besides antibacterial properties of DDAC, absorbed and eliminated the hydrophobic pathological microorganisms, whereas the hydrophilic nanofibers consisted of CS/PEO, increased the cell adhesion and proliferation due to positive charge of CS. Finally, we were able to increase the wound healing quality by using multifunctional wound dressing. CS/PEO-PCL containing 8 wt % of DDAC nanofibrous mats is promising as a wound dressing for wound management due to the favorable interactions between the pathogenic bacteria and PCL/CS-based wound dressing.
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http://dx.doi.org/10.1002/jbm.b.34636DOI Listing
November 2020

Evaluation radioprotective effect of curcumin conjugated albumin nanoparticles.

Bioorg Chem 2020 07 7;100:103891. Epub 2020 May 7.

Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran; Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

In this research, curcumin (CUR) conjugated albumin based nanoparticles (BSA-CUR) were designed for improvement and evaluation radioprotective effect of CUR. In this way, we have prepared BSA-CUR by covalently binding the CUR with BSA. Next, this synthesized prodrug was evaluated for physical and chemical properties by Fourier-transform infrared (FTIR), Dynamic light scattering (DLS), Transmission electron microscopy (TEM), Ultraviolet-visible (UV/Vis), and Differential scanning calorimetry (DSC) analysis. Furthermore, the chemical stability of designed prodrug was appraised. The result shows that the size of nanoparticles is 174.4 nm with a polydispersity index (PdI) of 0.191. The nanoparticles have a high loading capacity and show sustained release behavior. Loading of CUR to BSA not only could increase the chemical stability of CUR, but also could improve radioprotection efficacy of it's against X-Ray irradiation. The HHF-2 cells show 107% viability in the presence of BSA-CUR at a concentration of 50 µg/mL, whereas non-treated cells show 46% viability, under X-Ray irradiation. Also in vivo study results show that, four out of five mice have died when the mice irradiated by X-Ray and no received any treatment. Although, for a group that treated with BSA-CUR and also irradiated by X-Ray, median survival and survival rate was higher than CUR treated and control mice, and only two out of five mice have died. The result of this study proved that BSA-CUR can be used as a proficient vehicle for improving the potential radioprotective effect of CUR.
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http://dx.doi.org/10.1016/j.bioorg.2020.103891DOI Listing
July 2020

Anticancer effect of X-Ray triggered methotrexate conjugated albumin coated bismuth sulfide nanoparticles on SW480 colon cancer cell line.

Int J Pharm 2020 May 9;582:119320. Epub 2020 Apr 9.

Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address:

The application of nanoparticles (NPs) as radio-sensitizers and carriers has opened up a new horizon to overcome the limitations of chemo and radiotherapy. In this study, bovine serum albumin-coated BiS NPs (BiS@BSA NPs) were synthesized and evaluated in terms of their ability to be used as a radio-sensitizer and carrier for methotrexate (MTX). Physicochemical properties of MTX conjugated BiS@BSA NPs (BiS@BSA-MTX NPs) were characterized by DLS, TEM, FTIR, UV/Vis, and XRD analyses. After the evaluation of cellular uptake and intracellular localization, the cytotoxicity of the combination of BiS@BSA-MTX NPs and X-Ray radiation was analyzed against the SW480 cell line. The synthesized NPs exhibited spherical-like shapes and homogenous morphology, possessing a hydrodynamic diameter of 140.2 ± 5.71 nm (mean ± SD) and zeta potential of -25 mV. Also, the release study showed that the release of MTX is faster and higher in the presence of the proteinase K enzyme than the absence of the enzyme. The results of in-vitro chemo-radiation therapy indicated that the viability of treated cells with BiS@BSA-MTX NPs is significantly lower than the cells treated with BiS@BSA NPs. Furthermore, cells treated with BiS@BSA-MTX NPs showed a lower degree of viability when combined with X-Ray radiation in comparison with the absence of irradiation, which confirmed the ability of the BiS@BSA-MTX NPs as radio-sensitizer.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119320DOI Listing
May 2020

Natural biomacromolecule based composite scaffolds from silk fibroin, gelatin and chitosan toward tissue engineering applications.

Int J Biol Macromol 2020 Jul 13;154:1285-1294. Epub 2019 Nov 13.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Natupolymer-based scaffolds can increase cell affinity to biomaterials and improve cell responses. Silk fibroin, chitosan and gelatin that mimic the properties of natural extra-cellular matrix (ECM) were chosen due to their biocompatibility, biodegradability and less immunogenic reactions. We prepared composite scaffolds with different blending ratios of silk fibroin-chitosan-gelatin by freeze-drying technique. Silk fibroin was extracted from the Bombyx mori silkworm. The scaffolds were characterized by scanning electron microscopy (SEM), surface wettability, swelling measurements, In Vitro enzymatic degradation measurements and tensile test. The composite scaffolds showed pore sizes from 125 μm to 175 μm, good interconnectivity between pores and suitable porosity which are desirable for cell growth. The addition of chitosan-gelatin to silk fibroin increased water uptake and degradation rate and reduced mechanical strength but silk fibroin affect reversely on the degradation and mechanical strength of composite scaffolds. Biocompatibility of scaffolds was demonstrated by MTT-assay and hematoxylin-eosin (H&E) staining which lead to the growth and adhesion of endothelial cells. In this study, the fabricated composite scaffolds have the potential for tissue engineering applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.11.003DOI Listing
July 2020

Facile green synthesis of bismuth sulfide radiosensitizer biomineralization of albumin natural molecule for chemoradiation therapy aim.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):3832-3838

Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences , Zanjan , Iran.

High atomic number Z, nanoparticles are able to enhance the photoelectric and Compton effects under X-Ray irradiation resulting the increase of radiation therapy efficacy. To achieve enhanced radiation therapy, BiS biocompatible particles coated with bovine serum albumin (BSA) (BiS@BSA HNPs) were prepared through a BSA-mediated biomineralization procedure under green conditions. Then, to achieve improved chemo-radiation therapy against HT-29 cancer cells, curcumin (CUR) as natural anti-cancer therapy agent loaded on the BiS@BSA (BiS@BSA@CUR HNPs). Next, this synthesized nanodrug was evaluated for physical and chemical properties and in vitro cytotoxicity studies. Here, in vitro enhanced chemo-radiation combination therapy power was evaluated against HT-29 cell line under 2 Gy and 6 Gy X-ray irradiation doses. The BiS@BSA HNPs without irradiation rarely affect cell viability which shown the non-toxicity of BiS@BSA HNPs. The result of this study proved that BiS@BSA@CUR HNPs can be used as both proficient vehicles for effective delivery of CUR and radiosensitizer in the treatment of cancer. In addition, the result of this study confirmed that the combination of high Z-element nanoradiosensitizer, BiS@BSA HNPs, with a natural anti-cancer drug, CUR, enhanced therapeutic power against HT-29 cells.
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http://dx.doi.org/10.1080/21691401.2019.1669624DOI Listing
December 2019

Tumor Targeted Albumin Coated Bismuth Sulfide Nanoparticles (BiS) as Radiosensitizers and Carriers of Curcumin for Enhanced Chemoradiation Therapy.

ACS Biomater Sci Eng 2019 Sep 22;5(9):4416-4424. Epub 2019 Aug 22.

Department of pharmaceutical biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan 45139-56111, Iran.

Combination therapy such as radiotherapy combined with chemotherapy has attracted excessive interest in the new cancer research area. Therefore, developing nanobiomaterials for combination of radiotherapy and chemotherapy is required for more powerful and successful cures. Because of the amazing X-ray sensitization proficiency of Bi based nanoparticles, in this work, we synthesized and used BiS as an enhancer of X-ray radiation therapy, and furthermore, BiS served as carrier of curcumin (CUR), a chemotherapy drug, for the goal of combination therapy. Additionally, we selected and conjugated folic acid (FA) as a targeting molecule for the direction of the designed system to the tumor site. After characterization of drug loaded FA conjugated BiS@BSA nanoparticles (BiS@BSA-FA-CUR) and and safety assessment, we applied it for enhanced chemotherapy and X-ray radiation therapy in cancer cells and a tumor bearing mice model. Moreover, the CT contrast ability of synthesized nanoparticles was examined. Here, we (1) for the first time developed the novel and targeted CUR loaded BiS@BSA (BiS@BSA-FA-CUR) to promote chemoradiation therapy in 4T1 cells and breast tumor in mice; (2) found the synthesized nanoparticles to have good stability; (3) injected a single dose of the designed radiosensitizer for cancer therapy; and (4) used a conventional X-ray dose, 2Gy, for X-ray radiation therapy. The result of X-ray radiotherapy shows that the mice tumors vanished near 3 weeks after radiation. Interestingly, these results show that BiS@BSA-FA-CUR with the aid of X-ray can clearly promote the efficacy of chemoradiation therapy.
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http://dx.doi.org/10.1021/acsbiomaterials.9b00489DOI Listing
September 2019

Methotrexate anticancer drug delivery to breast cancer cell lines by iron oxide magnetic based nanocarrier.

J Biomed Mater Res A 2019 11 31;107(11):2492-2500. Epub 2019 Jul 31.

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

In this study, we have achieved to provide an efficient method for production of iron oxide magnetic nanoparticles (MNPs) with arginine capping using in situ and one-pot co-precipitation method. As a novel drug delivery system, methotrexate (MTX) was conjugated to the obtained nanoparticles. These MNPs conjugate can potentially use in controlled drug delivery as carrier, and in magnetic resonance imaging as a contrast agent. Also, these nanoparticles can serve as a target in cancer therapy and diagnosis. These MNPs were covalently bond with MTX and can target the majority of cancer cells that their surfaces overexpressed by folate receptors. These conjugated nanoparticles were obtained through amide bond between the amine groups on their surface and the carboxylic acid end groups on MTX due to being functionalized with arginine. MTX was cleaved from nanoparticles according to drug release experiments in the presence of protease-like lysosomal conditions. Fe-Arg-MTX was characterized by transmission electron microscopes, dynamic light scattering, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. Furthermore, vibrating sample magnetometry analysis showed excellent magnetic properties of them. The average particle size of Fe-Arg-MTX was approximately 27 nm. The result revealed that the bare nanoparticles have no cytotoxicity against MCF-7, 4T1, and HFF-2 cell lines. Hemolysis assay showed that these nanoparticles are biocompatible. Regarding the research success, an efficient technique can be presented for drug delivery and controlled release and for studying cancer-fighting in alive creature's bodies.
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http://dx.doi.org/10.1002/jbm.a.36755DOI Listing
November 2019

Multifunctional nanoparticles from albumin for stimuli-responsive efficient dual drug delivery.

Bioorg Chem 2019 07 29;88:102959. Epub 2019 Apr 29.

Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address:

In this project methotrexate (MTX) conjugated albumin based nanoparticles (MTX-BSA) loaded with curcumin (CUR) drug (CUR-MTX-BSA) for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy were designed. Co-delivery is a new strategy which minimize the amount of each drug, reduce of side effects and also to achieve the synergistic effect for cancer therapies. The MTX was conjugated to albumin via covalent bond. Next, this synthesized prodrug loaded with CUR. Afterward, the formulations were evaluated for physical and chemical properties by DLS, TEM, FTIR, UV/Vis, DSC analysis, in vitro cytotoxicity and in vivo biocompatibility studies. Furthermore, the drug loading and release study were evaluated. Proteinase K enzyme was used to break amid bond between MTX and BSA and also amidic bonds in BSA structure. Administration of up to 2000 mg/kg of BSA to healthy animals was non-toxic and all treated mice were still alive after 24 h. The result of this study proved that CUR-MTX-BSA can be used as a proficient vehicle for effective co-delivery of CUR and MTX in the treatment of cancer.
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http://dx.doi.org/10.1016/j.bioorg.2019.102959DOI Listing
July 2019

New Insight about Biocompatibility and Biodegradability of Iron Oxide Magnetic Nanoparticles: Stereological and In Vivo MRI Monitor.

Sci Rep 2019 05 9;9(1):7173. Epub 2019 May 9.

Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Iron oxide magnetic nanoparticles (IONPs) have attracted enormous attention because of their extensive medicinal and industrial applicability. PEGylated L-arginine modified iron oxide magnetic nanoparticles (PEG-Arg@IONPs) were synthesized and functioned in the present research as MRI contrast agents considered in vivo BALB/c model. The Synthesized PEG-Arg@IONPs were tracked in certain time intervals by MRI. The intensity of MR imaging of kidneys increased after administration of PEG-Arg@IONPs, which could confirm the emission of these nanoparticles by kidneys shortly after administration. Although PEG-Arg@IONPs were uptake by liver within 2 hours after injection, whereas, the signal change intensity of spleen, heart and kidneys confirmed that PEG-Arg@IONPs existed in other organs. The results illustrated that IONPs coated with PEGylated natural amino acid thin layers had a long circulation time and could be served as T contrast agents for diagnosis purpose. Notably, to the best of our knowledge, it was the first time the biocompatibility and biodegradability of IONPs was studied and evaluated by stereological and MRI technique.
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http://dx.doi.org/10.1038/s41598-019-43650-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509211PMC
May 2019

Polyethylene glycol (PEG) decorated graphene oxide nanosheets for controlled release curcumin delivery.

Heliyon 2019 Apr 10;5(4):e01466. Epub 2019 Apr 10.

Department of Pharmaceutical Biomaterials, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

Nowadays, the use of nanostructures in various medical and biological fields such as drug delivery in cancer treatment is increasing. Among the nanostructures, graphene oxide (GO) is an excellent candidate for drug delivery application because of its unique properties. For more stability, GO can bind with various polymers by its carboxyl, hydroxyl and epoxy functional groups. In this study, firstly GO synthesized by the improved Hummers chemical method and then polyethylene glycol polymer was conjugated to it by using EDC/NHS catalyst. Finally, curcumin (Cur) as anti-cancer drug has been loaded onto the PEGylated graphene oxide (GO-PEG). Next, curcumin loaded onto PEGylated graphene oxide (GO-PEG-Cur) were evaluated by using ultraviolet, Fourier transform infrared spectroscopy, differential scanning calorimeter, atomic microscopic force and dynamic light scattering. The amount of loaded drug was calculated about 4.5% with the help of the standard curcumin curve and UV/Vis spectrometer. Also, the result of release shows that maximum drug release rate for this nanocarrier in pH 5.5 and 7.4 was measured 50% and 60%, respectively, after 96 hours. The results showed that the zeta-potential analysis of GO-PEG-Cur was about -13.9 mV that expresses a negative surface charge for produced nanocarrier.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460424PMC
April 2019

Biotin-functionalized copolymeric PEG-PCL micelles for in vivo tumour-targeted delivery of artemisinin.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):104-114

b Zanjan Pharmaceutical Biotechnology Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.

Artemisinin is used as an antimalarial and anticancer agent with minimal toxic effects on the host body. Biotin-PEG-PCL polymers have been used for targeted drug delivery to cancer, as well as to improve the pharmacokinetics of the drug and reduce its effects. In this study, biotin-conjugated copolymers were fabricated with polymerization of the ring opening method and the properties of copolymer and nanoparticles were investigated using various techniques. The toxicity of artemisinin and its nanoparticles have been investigated on MCF-7 and normal HFF2 cells. The results showed that the encapsulation efficacy of artemisinin in nanoparticles was 45.5 ± 0.41%. The release profile of the drug indicates that the release is slow and controlled and is approximately pH dependent. The results of artemisinin cell culture on human breast cancer cells showed that biotin-PEG-PCL nanoparticles had an inhibitory effect on MCF-7 cells and had no toxic effects on HFF2 cells. Anticancer activity in vivo in the 4T1 breast cancer model showed that tumour volumes were decreased up 40 mm by ART-loaded micelles and 76 mm by free ART, compared to the control group (2150 mm). In vivo results showed that this formulation significantly increases the accumulation of substances in the tumours. Therefore, the molecular formulation of ART-based copolymers can be a desirable process for cancer treatment purposes.
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http://dx.doi.org/10.1080/21691401.2018.1543199DOI Listing
December 2019

Preparation, characterization, and evaluation of amino acid modified magnetic nanoparticles: drug delivery and MRI contrast agent applications.

Pharm Dev Technol 2018 Dec 9;23(10):1156-1167. Epub 2018 Nov 9.

a Zanjan Pharmaceutical Nanotechnology Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.

This study is a report about the synthesis iron oxide magnetic nanoparticles (IONPs) which modified with positive and negative charged amino acids (AAs). l-Arginine (Arg) and l-aspartic acid (Asp) which have of guanidinium and carboxylic acid groups, respectively, were selected for this study. After loading chrysin in amino acids modified iron oxide magnetic nanoparticles (F@AAs@Chrysin NPs), it was characterized by XRD, TGA, FTIR, VSM, and TEM techniques. Finally, MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AA coated IONPs. The results show that, the ζ-potential and average size of F@Arg@chrysin NPs and F@Asp@chrysin NPs were to -3.87, -2.12 mV, 18.75 ± 2.40 (mean ± SD ( = 50)) nm, and 19.86 ± 2.22 (mean ± SD ( = 48)) nm, respectively. Also, the results indicated that these F@AAs@Chrysin NPs were appropriate for delivery of chrysin. Furthermore, the phantom MRI studies showed the IONPs can be used as contrast agent for the revealing of tumor.
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http://dx.doi.org/10.1080/10837450.2018.1536995DOI Listing
December 2018

Phenyl alanine & Tyrosine Amino acids Coated Magnetic Nanoparticles: Preparation and Toxicity study.

Drug Res (Stuttg) 2019 May 6;69(5):277-283. Epub 2018 Sep 6.

Student Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

In this study we reported the synthesis of L-phenyl alanine (Phe) & L-tyrosine (Tyr) Natural Amino acids coated iron oxide magnetic nanoparticles under one-pot and in situ reaction. Functionalized iron oxide magnetic nanoparticles were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Vibrating Sample Magnetometer (VSM), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) techniques. Cellular toxicity of amino acids coated iron oxide magnetic nanoparticles was also investigated on HEK-293 cell lines. Additionally, a hemolysis test of as prepared magnetic nanoparticles were performed. It was found that the synthesized Phe and Tyr coated magnetic nanoparticles (F@Phe NPs and F@Tyr NPs) were spherical in shape with an average size less than 25 nm, also the saturation magnetization (Ms) of the F@Phe NPs and F@Tyr NPs were about 30.02 and 58.23 emu/g, respectively, which was lower than those of bare FeO. The TGA results show that apart from this weight loss, the coated sample shows a weight loss of 5.48, and 6.88% respectively corresponding to loss of Tyr, and Phe which is coated on the FeO nanoparticles. At a high concentration, less than 2.92 and 3.13% hemolytic activity were observed for F@Phe NPs and F@Tyr NPs, respectively. The F@Phe NPs and F@Tyr NPs show the possibility of using this nanoparticles in the development of in vitro and in vivo pharmaceutical and biomedical fields due to do not possess a toxic effect, good ζ-potential and related small and narrow size distribution.
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http://dx.doi.org/10.1055/a-0664-0431DOI Listing
May 2019

Preparation, characterization and in vitro anticancer activity of paclitaxel conjugated magnetic nanoparticles.

Drug Dev Ind Pharm 2018 Nov 5;44(11):1895-1903. Epub 2018 Sep 5.

a Chemical Engineering Faculty , Sahand University of Technology , Tabriz , Iran.

In this study, magnetic nanoparticles (MNPs) coated with L-aspartic acid (F-Asp NPs) were synthesized through a co-precipitation method and conjugated with paclitaxel (PTX) (F-Asp-PTX NPs) by esterification reaction between the carboxylic acid end groups on MNPs surface and the hydroxyl groups of the PTX and studied its cytotoxic effect in vitro. The successful conjugating of PTX onto the nanoparticles (NPs) was confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) techniques. The results showed that the average size was 46.11 ± 7.8 (mean ± SD (n = 25)) nm. The cytotoxicity of void of PTX and F-Asp-PTX NPs were compared to each other by MTT assay of the treated MCF-7 cell line. The F-Asp-PTX NPs showed pH-dependent drug release behavior. These studies specify that F-Asp-PTX NPs have a very remarkable anticancer effect, for breast cancer cell line.
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http://dx.doi.org/10.1080/03639045.2018.1508222DOI Listing
November 2018

Folic acid conjugated bovine serum albumin: An efficient smart and tumor targeted biomacromolecule for inhibition folate receptor positive cancer cells.

Int J Biol Macromol 2018 Oct 6;117:1125-1132. Epub 2018 Jun 6.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

This work described a folic acid conjugated delivery of chrysin-loaded bovine serum albumin nanoparticles, which could overcome the nonspecific targeting disadvantage. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid which have some significant biological effects on the processes of chemical defense. Chrysin loaded bovine serum albumin nanoparticles (Chrysin-BSA NPs) were synthesized by a simple desolvation procedure. Afterward, folic acid (FA) was conjugated to the surface of Chrysin-BSA NPs by carbodiimide chemistry (Chrysin-BSA-FA NPs). The resultant Chrysin-BSA-FA NPs showed a spherical shape, with a hydrodynamic diameter of 97.5 ± 5.8 nm (mean ± SD) nm and a ζ-potential of -11.3 mV. The in vitro drug release study of chrysin presented a sustained and controlled release pattern. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. Both the Chrysin-BSA NPs and Chrysin-BSA-FA NPs prompted an enhanced cancer cell cytotoxic effect in contrast to chrysin solution. These data recommended that the folate-modified chrysin -loaded vehicle, which demonstrated better biocompatibility and potential superiority, could be a suitable cancer therapy in targeting tumors in the future.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.06.026DOI Listing
October 2018

Theranostic nanoparticles based on magnetic nanoparticles: design, preparation, characterization, and evaluation as novel anticancer drug carrier and MRI contrast agent.

Drug Dev Ind Pharm 2018 Oct 4;44(10):1668-1678. Epub 2018 Jul 4.

a Student Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.

In this work, we reported the synthesis of curcumin (CUR)-loaded hydrophilic and hydrophobic natural amino acids (AAs)-modified iron oxide magnetic nanoparticles (IONPs). Two types of AAs, l-lysine (Lys) and l-phenylalanine (PhA), were selected to study their effects on loading capacity, release profile of CUR, biocompatibility, and anticancer activity. CUR-loaded AAs-modified IONPs (F@AAs@CUR NPs) were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. Next, the various kinetic equations were fitted to the release data of CUR from F@Lys@CUR NPs and F@PhA@CUR NPs. Additionally, hemolysis test and MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AAs-coated IONPs. Finally, the anticancer activity of F@AAs@CUR NPs examined on MCF-7 breast cancer cell line. The results indicate that these nanocarriers are nontoxic and biocompatible and also F@AAs@CUR NPs are suitable carriers for delivery of curcumin and even other hydrophobic drugs. Also, the MRI training established the effectiveness of IONPs as contrast agent for the revealing of tumor as evidenced from the phantom images as well as higher T relaxivity.
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http://dx.doi.org/10.1080/03639045.2018.1483398DOI Listing
October 2018

Production of biological nanoparticles from bovine serum albumin as controlled release carrier for curcumin delivery.

Int J Biol Macromol 2018 Aug 10;115:83-89. Epub 2018 Apr 10.

Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address:

This study described a curcumin (CUR) loaded bovine serum albumin nanoparticles (BSA@CUR NPs), which could solubilize the poorly water-soluble drug and increase the therapeutic efficacy of the drug. BSA@CUR NPs were synthesized by a simple coacervation procedure. The resultant BSA@CUR NPs showed a spherical shape, with a diameter of 92.59±16.75nm (mean ± SD) nm and a ζ-potential of - 9.19mV. The in vitro drug release study of CUR showed a sustained and controlled release pattern. Cellular toxicity of BSA NPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared NPs were performed for investigation of hemocompatibility. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. The in vitro anticancer activity of the BSA@CUR NPs were performed by MTT assay on MCF-7 cancer cells. These results suggest that BSA@CUR NPs are a new drug delivery system for cancer therapy.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.04.043DOI Listing
August 2018

PAMAM-modified citric acid-coated magnetic nanoparticles as pH sensitive biocompatible carrier against human breast cancer cells.

Drug Dev Ind Pharm 2018 Aug 23;44(8):1377-1384. Epub 2018 Mar 23.

c Cancer Gene Therapy Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.

Denderimer-modified magnetic nanoparticles are a promising drug delivery nanosystem which can improve the therapeutic efficacy of chemotherapy drugs and can also be beneficial as magnetic resonance (MR) images contrast agent. The present study introduces the preparation and characterization of the potential therapeutic efficiency of curcumin (CUR)-loaded denderimer-modified citric acid coated FeO NPs. Polyamidoamine (PAMAM, generation G) was used to encapsulate citric acid coated FeO nanoparticles. The successful preparation of CUR-loaded nanocarriers were confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. The loading capacity and encapsulation efficiency of CUR molecules were 12 ± 0.03% and 45.58 ± 0.41%, respectively. The anticancer effect of void CUR and CUR-loaded nanocarriers were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on treated MCF-7 cell line. It can be concluded that application of nanoparticles can be more effective strategy for controlled and slow release of CUR in human breast cancer treatment.
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http://dx.doi.org/10.1080/03639045.2018.1451881DOI Listing
August 2018

Enzymatic stimuli-responsive methotrexate-conjugated magnetic nanoparticles for target delivery to breast cancer cells and release study in lysosomal condition.

J Biomed Mater Res A 2018 06 5;106(6):1646-1654. Epub 2018 Mar 5.

Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

In this study, magnetic nanoparticles (MNPs) coated with glycine (F-Gly NPs) and conjugated with methotrexate (MTX) (F-Gly-MTX NPs) were synthesized through a coprecipitation method followed by amidation reaction between the carboxylic acid end groups on MTX and the amine groups on the MNPs surface and studied its cytotoxic effect in vitro. The successful conjugating of MTX onto the nanoparticles (NPs) was confirmed by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The results showed that the average size was 46.82 ± 5.03 nm. This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. Hemolysis assay and cytotoxicity study results on HFF-2 and HEK-293 cell lines show that as prepared MNPs are biocompatible. The cytotoxicity of void of the MTX and F-Gly-MTX NPs were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of the treated MCF-7 cell line. Enzymatic release studies exhibited the release of the MTX via peptide bond cleavage in the presence of proteinase K. These studies specify that the F-Gly-MTX NPs have a very remarkable anticancer effect, for breast cancer cell line. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1646-1654, 2018.
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http://dx.doi.org/10.1002/jbm.a.36364DOI Listing
June 2018

Bovine Serum Albumin (BSA) coated iron oxide magnetic nanoparticles as biocompatible carriers for curcumin-anticancer drug.

Bioorg Chem 2018 02 2;76:501-509. Epub 2018 Jan 2.

Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address:

The bovine serum albumin-coated magnetic nanoparticles (F@BSA NPs) were prepared as curcumin (CUR) carriers through desolvation and chemical co-precipitation process. The characteristics of CUR loaded F@BSA NPs (F@BSA@CUR NPs) were determined by X-ray diffraction (XRD), thermogravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrating-sampling magnetometry (VSM) techniques. It was found that the synthesized F@BSA@CUR NPs were spherical in shape with an average size of 56 ± 11.43 nm (mean ± SD (n = 33)), ζ-potential of -10.1 mV, and good magnetic responsivity. Meanwhile, the drug content of the nanoparticles was 6.88%. These F@BSA@CUR NPs also demonstrated sustained release of CUR at 37 °C in different buffer solutions. Cellular toxicity of F@BSA@CUR NPs was studied on HFF2 cell line. Also, the cytotoxicity of F@BSA@CUR NPs towards MCF-7 breast cancer cells was investigated. The results revealed that F@BSA@CUR NPs have significant cytotoxicity activity on MCF-7 cell line.
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http://dx.doi.org/10.1016/j.bioorg.2017.12.033DOI Listing
February 2018

Synthesis, characterization, and kinetic release study of methotrexate loaded mPEG-PCL polymersomes for inhibition of MCF-7 breast cancer cell line.

Pharm Dev Technol 2019 Jan 18;24(1):89-98. Epub 2018 Jan 18.

c Cancer Gene Therapy Research Center , Zanjan University of Medical Sciences , Zanjan , Iran.

In this study, we designed a polymersome system for the controlled release of methotrexate (MTX) as an anticancer drug with the objective of improving the loading efficiency of the drug in polymersomes as well as achievement of an efficient control on the release rate of drug from nanocarriers. We synthesized mono methoxy poly(ethylene glycol)-poly(e-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by proton nuclear magnetic resonance spectroscopy (H NMR), Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) techniques. MTX was encapsulated within nanoparticles (NPs) through multiple emulsion method. The resulting NPs were characterized further by various techniques such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Next, the various kinetic equations were fitted to the release data of MTX from MTX-loaded mPEG-PCL polymersomes. The results showed that the zeta potential of MTX-loaded mPEG-PCL polymersomes was about -5.49 mV and the average size was 49.18 nm. MTX was encapsulated into polymersomes loading capacity of 12 ± 0.09% and encapsulation efficiency of 45.5 ± 0.41%. The metabolic activity assays of void of MTX, mPEG-PCL polymersomes, and MTX-loaded mPEG-PCL polymersomes were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of the treated MCF-7 cell lines. It can be concluded that application of NPs is a better and more effective strategy for controlled and slow release of MTX in the treatment of cancer.
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http://dx.doi.org/10.1080/10837450.2018.1425433DOI Listing
January 2019