Publications by authors named "Hossein Derakhshankhah"

30 Publications

  • Page 1 of 1

3D bioprinting of engineered breast cancer constructs for personalized and targeted cancer therapy.

J Control Release 2021 Mar 25;333:91-106. Epub 2021 Mar 25.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address:

The bioprinting technique with specialized tissue production allows the study of biological, physiological, and behavioral changes of cancerous and non-cancerous tissues in response to pharmacological compounds in personalized medicine. To this end, to evaluate the efficacy of anticancer drugs before entering the clinical setting, tissue engineered 3D scaffolds containing breast cancer and derived from the especially patient, similar to the original tissue architecture, can potentially be used. Despite recent advances in the manufacturing of 3D bioprinted breast cancer tissue (BCT), many studies still suffer from reproducibility primarily because of the uncertainty of the materials used in the scaffolds and lack of printing methods. In this review, we present an overview of the breast cancer environment to optimize personalized treatment by examining and identifying the physiological and biological factors that mimic BCT. We also surveyed the materials and techniques related to 3D bioprinting, i.e, 3D bioprinting systems, current strategies for fabrication of 3D bioprinting tissues, cell adhesion and migration in 3D bioprinted BCT, and 3D bioprinted breast cancer metastasis models. Finally, we emphasized on the prospective future applications of 3D bioprinted cancer models for rapid and accurate drug screening in breast cancer.
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http://dx.doi.org/10.1016/j.jconrel.2021.03.026DOI Listing
March 2021

Biomaterials in Valvular Heart Diseases.

Front Bioeng Biotechnol 2020 9;8:529244. Epub 2020 Dec 9.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Valvular heart disease (VHD) occurs as the result of valvular malfunction, which can greatly reduce patient's quality of life and if left untreated may lead to death. Different treatment regiments are available for management of this defect, which can be helpful in reducing the symptoms. The global commitment to reduce VHD-related mortality rates has enhanced the need for new therapeutic approaches. During the past decade, development of innovative pharmacological and surgical approaches have dramatically improved the quality of life for VHD patients, yet the search for low cost, more effective, and less invasive approaches is ongoing. The gold standard approach for VHD management is to replace or repair the injured valvular tissue with natural or synthetic biomaterials. Application of these biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of this type of heart disease. The focus of the present review is the current use of different types of biomaterials in treatment of valvular heart diseases.
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http://dx.doi.org/10.3389/fbioe.2020.529244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793990PMC
December 2020

Stimuli-responsive natural gums-based drug delivery systems for cancer treatment.

Carbohydr Polym 2021 Feb 22;254:117422. Epub 2020 Nov 22.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Chemotherapy as the main cancer treatment method has non-specific effects and various side-effects. Accordingly, significant attempts have been conducted to enhance its efficacy through design and development of "smart" drug delivery systems (DDSs). In this context, natural gums, as a nice gift by the nature, can be exploited as stimuli-responsive DDSs for cancer treatment in part due to their renewability, availability, low cost, bioactivity, biocompatibility, low immunogenicity, biodegradability, and acceptable stability in both in vitro and in vivo conditions. However, some shortcomings (e.g., poor mechanical properties and high hydration rate) restrict their biomedical application ranges that can be circumvented through modification process (e.g., grafting of stimuli-responsive polymers or small molecules) to obtain tailored biomaterials. This review article aimed to compile the stimuli-responsive DDSs based on natural gums. In addition, different types of stimuli, the fundamental features of natural gums, as well as their chemical modification approaches are also shortly highlighted.
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http://dx.doi.org/10.1016/j.carbpol.2020.117422DOI Listing
February 2021

A novel bioreducible and pH-responsive magnetic nanohydrogel based on β-cyclodextrin for chemo/hyperthermia therapy of cancer.

Carbohydr Polym 2021 Jan 16;252:117229. Epub 2020 Oct 16.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

A new strategy for design and development of a magnetic "smart" drug delivery system (DDS) based on β-cyclodextrin (β-CD) and poly(2-ethyl-2-oxazoline) (PEtOx) was reported. For this purpose, a β-CD-(I) was acetylated, and then EtOx monomer was grafted onto the acetylated β-CD-(I) through cationic ring-opening polymerization followed by simultaneous crosslinking with amine-end capped FeO nanoparticles (FeO-NH NPs) and cystamine to produce a β-CD-g-(PEtOx)/FeO as a reduction- and pH-responsive magnetic DDS. The developed magnetic nanohydrogel was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies, as well as its pH- and reduction-triggered drug release behaviors were investigated. The anticancer activity of the formulated β-CD-g-(PEtOx)/FeO-Dox was investigated against MCF7 cells. According to the results, the formulated β-CD-g-(PEtOx)/FeO-Dox can be considered as an efficient and "smart" DDS for cancer therapy and diagnosis due to its high drug loading value (∼ 74 %), slow and stimuli-triggered drug release behavior, and acceptable magnetic properties.
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http://dx.doi.org/10.1016/j.carbpol.2020.117229DOI Listing
January 2021

A novel multi-stimuli-responsive nanomedicine based on FeO@Au nanoparticles against cancer.

Drug Dev Ind Pharm 2020 Nov 18;46(11):1832-1843. Epub 2020 Sep 18.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

A novel multi-stimuli-responsive nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly(-isopropylacrylamide--acrylic acid) (HS-PNIPAAm--PAA) onto FeO@Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, FeO@Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm--PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized FeO@Au NPs by Au-S bonding. The Dox loading capacity of the synthesized FeO@Au/Polymer NPs was calculated to be 81%. The nanomedicine exhibited excellent drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated FeO@Au/Polymer has high potential as nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and FeO nanomaterials in its structure.
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http://dx.doi.org/10.1080/03639045.2020.1821052DOI Listing
November 2020

Human plasma protein corona decreases the toxicity of pillar-layer metal organic framework.

Sci Rep 2020 09 3;10(1):14569. Epub 2020 Sep 3.

Department of Chemistry, Faculty of Chemical Science, Firoozabad Branch, Islamic Azad University, P.O. Box 74715-117, Firoozabad, Fars, Iran.

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal-organic framework (MOF) in human plasma. The [Cu(L)(L)].1.3DMA (MOF-1) {L = 4, 4-bipyridine and L = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, β and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.
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http://dx.doi.org/10.1038/s41598-020-71170-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471913PMC
September 2020

Interactions of insulin with tragacanthic acid biopolymer: Experimental and computational study.

Int J Biol Macromol 2020 Dec 16;164:321-330. Epub 2020 Jul 16.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran; Medical Biology Research Center, Health Technologies Institute, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran. Electronic address:

Alternative methods for insulin delivery instead of subcutaneous injection in diabetic patients is of great essential, and biocompatible polymers are one of the most efficient vehicles for this purpose. This research aims to investigate the capability of tragacanthic acid (TA) to bind insulin and release it under physiological conditions without alteration in the structure and conformation of insulin. Interactions between TA and insulin were studied using spectroscopic techniques and computational modeling by docking and molecular dynamics simulations. Our results demonstrate an entropy-driven spontaneous interaction between insulin and TA, where hydrogen bonds act as the main enthalpic contribution. According to our findings, the weak interaction between insulin and TA provides the basis for efficient capture and appropriate release of insulin by TA as a potential part of the insulin delivery system. In conclusion, tragacanth acid can be a proper candidate for insulin delivery.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.122DOI Listing
December 2020

Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: in vitro and in vivo studies.

Sci Rep 2020 05 20;10(1):8312. Epub 2020 May 20.

Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

Functional wound dressing with tailored physicochemical and biological properties is vital for diabetic foot ulcer (DFU) treatment. Our main objective in the current study was to fabricate Cellulose Acetate/Gelatin (CA/Gel) electrospun mat loaded with berberine (Beri) as the DFU-specific wound dressing. The wound healing efficacy of the fabricated dressings was evaluated in streptozotocin-induced diabetic rats. The results demonstrated an average nanofiber diameter of 502 ± 150 nm, and the tensile strength, contact angle, porosity, water vapor permeability and water uptake ratio of CA/Gel nanofibers were around 2.83 ± 0.08 MPa, 58.07 ± 2.35°, 78.17 ± 1.04%, 11.23 ± 1.05 mg/cm/hr, and 12.78 ± 0.32%, respectively, while these values for CA/Gel/Beri nanofibers were 2.69 ± 0.05 MPa, 56.93 ± 1°, 76.17 ± 0.76%, 10.17 ± 0.21 mg/cm/hr, and 14.37 ± 0.42%, respectively. The antibacterial evaluations demonstrated that the dressings exhibited potent antibacterial activity. The collagen density of 88.8 ± 6.7% and the angiogenesis score of 19.8 ± 3.8 obtained in the animal studies indicate a proper wound healing. These findings implied that the incorporation of berberine did not compromise the physical properties of dressing, while improving the biological activities. In conclusion, our results indicated that the prepared mat is a proper wound dressing for DFU management and treatment.
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http://dx.doi.org/10.1038/s41598-020-65268-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239895PMC
May 2020

Irreversible thermal inactivation and conformational lock of alpha glucosidase.

J Biomol Struct Dyn 2020 May 14:1-7. Epub 2020 May 14.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

In the present work, we studied the structure-activity relationship and kinetics of thermal inactivation of α-glucosidase A (AglA) in a 50 mM potassium phosphate buffer at pH 6.8 using -nitrophenyl α-d-glucopyranoside (NPG) as the synthetic substrate following absorbance at 410 nm by UV-Vis spectrophotometer. The interface structure and residual activity plot were analyzed via biochemical measurements by means of conformational lock theory, as well. The thermal inactivation curves were plotted in temperature interval from 30 to 50 °C. Based on experimental and structural data we suggested intermediates during inactivation before the loss of enzyme activity. Arrhenius plot for thermal inactivation rate constant showed biphasic appearance related to before and after 45°C temperature. The contact areas between two subunits were ruptured and unlocked stepwise during dimer dissociation. Cleavage of these areas induced the dissociation of the subunits along with destruction of the active centers and subsequently the loss of activity. It seems that the contact areas interact with active centers by conformational changes involving secondary structural elements.
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http://dx.doi.org/10.1080/07391102.2020.1762742DOI Listing
May 2020

Nanozyme-based sensing platforms for detection of toxic mercury ions: An alternative approach to conventional methods.

Talanta 2020 Aug 17;215:120939. Epub 2020 Mar 17.

Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address:

Mercury (Hg) is known as a poisonous heavy metal which stimulates a wide range of adverse effects on the human health. Therefore, development of some feasible, practical and highly sensitive platforms would be desirable in determination of Hg level as low as nmol L or pmol L. Different approaches such as ICP-MS, AAS/AES, and nanomaterial-based nanobiosensors have been manipulated for determination of Hg level. However, these approaches suffer from expensive instruments and complicated sample preparation. Recently, nanozymes have been assembled to address some disadvantages of conventional methods in the detection of Hg. Along with the outstanding progress in nanotechnology and computational approaches, pronounced improvement has been attained in the field of nanozymes, recently. To accentuate these progresses, this review presents an overview on the different reports of Hg-induced toxicity on the different tissues followed by various conventional approaches validated for the determination of Hg level. Afterwards, different types of nanozymes like AuNPs, PtNPs for quantitative detection of Hg were surveyed. Finally, the current challenges and the future directions were explored to alleviate the limitation of nanozyme-based platforms with potential engineering in detection of heavy metals, namely Hg. The current overview can provide outstanding information to develop nano-based platforms for improvement of LOD and LOQ of analytical methods in sensitive detection of Hg and other heavy metals.
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http://dx.doi.org/10.1016/j.talanta.2020.120939DOI Listing
August 2020

A bio-inspired magnetic natural hydrogel containing gelatin and alginate as a drug delivery system for cancer chemotherapy.

Int J Biol Macromol 2020 Aug 13;156:438-445. Epub 2020 Apr 13.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

This study aimed to design and development of a magnetic natural hydrogel based on alginate (Alg), gelatin (Gel), and FeO magnetic nanoparticles (MNPs) as an efficient and "smart" drug delivery system (DDS) for cancer therapy. First, Alg was partially oxidized (OAlg), and then the Alg-Gel chemical hydrogel was synthesized through "Shift-Base" condensation reaction. Afterward, FeO NPs were incorporated into the hydrogel through in situ chemical co-precipitation approach. The scanning electron microscopy (SEM) image exhibited that the fabricated Alg-Gel hydrogel has porous microstructure without microphase separation. Transmission electron microscopy (TEM) revealed the well-defined formation of FeO NPs throughout the Alg-Gel hydrogel with spherical shapes in the size range of 25 ± 10 nm. Saturation magnetization (δ) value of the Alg-Gel/FeO was obtained to be 31 emu g that represent proper magnetic property for "smart" drug delivery purposes. The obtained Alg-Gel/FeO was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies as well as its anticancer activity was investigated against Hela cells. The formulated Alg-Gel/FeO-Dox exhibited pH-dependent drug release behavior due to presence of carboxylic acid groups in the DDS. According to the results, the Alg-Gel/FeO magnetic hydrogel can be considered as an efficient and "smart" DDS for cancer therapy and diagnosis.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.04.074DOI Listing
August 2020

Cell-Penetrating Peptides: As a Promising Theranostics Strategy to Circumvent the Blood-Brain Barrier for CNS Diseases.

Curr Drug Deliv 2020 ;17(5):375-386

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain.
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http://dx.doi.org/10.2174/1567201817666200415111755DOI Listing
January 2020

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin.

J Biomol Struct Dyn 2020 Apr 22:1-9. Epub 2020 Apr 22.

Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1754293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189411PMC
April 2020

Naturally occurring biological macromolecules-based hydrogels: Potential biomaterials for peripheral nerve regeneration.

Int J Biol Macromol 2020 Jul 18;154:795-817. Epub 2020 Mar 18.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Despite the recent advances in the treatment strategies of peripheral nerve system defects, peripheral nerve injury (PNI) is still one of the most important health issues with increasing incidence worldwide. The most commonly used treatment approaches are allografts, xenografts, and autologous, which have some drawbacks, including complications, limited source of the donor tissue, tubular collapse, and scar tissue formation. In this context, regenerative medicine has been introduced as a powerful approach to improve the healing process and obtain acceptable functional recovery in the injury site using living cells, scaffold, and bioactive (macro-) molecules. Amongst them, scaffold as a three-dimensional (3D) support biomaterial, structurally bridged the gap or site of injury in order to provide physical and chemical cues to promote correct reinnervation and functional regeneration. Amongst different scaffolding biomaterials, naturally occurring biological macromolecules (more especially proteins and polysaccharides)-based hydrogels exhibited promising results due to their fascinating physicochemical, as well as physiologically relevant properties. This review highlights the recent progress in the development of natural hydrogels-based neural scaffolds. Furthermore, PNI healing process, current status, and challenges are also shortly discussed.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.03.155DOI Listing
July 2020

Characterization and anti-diabetic effects of the oligosaccharide fraction isolated from Rosa canina in STZ-Induced diabetic rats.

Carbohydr Res 2020 Mar 24;489:107927. Epub 2020 Jan 24.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Diabetes mellitus is the most common metabolic disorder characterized by chronic hyperglycemia. There has been a surge of research studies aiming to use natural products in the management of diabetes. The objective of this study was to isolate and characterize the structure and anti-diabetic mechanisms of the main ingredient from Rosa canina. The oligosaccharide was isolated from Rosa canina fruits and characterized by a combination of FTIR, NMR and Mass spectrometry. Wistar rats were divided into negative control, diabetic (type 2), isolated oligosaccharide (IO)-treated diabetic and positive diabetic controls. Oral glucose tolerance, gluconeogenesis and α-glucosidase inhibitory tests as well as immunohistochemistry and quantitative real time-PCR were performed to elucidate the molecular anti-diabetic mechanisms of IO. Structural analyses confirmed the oligosaccharide structure of isolated fraction. Gluconeogenesis and α-glucosidase activity were inhibited by IO in diabetic rats. The oral glucose tolerance test was improved significantly in the group treated with the IO (P < 0.05). Pancreatic β-cells and tissue pathological examination showed a significant improvement after the treatment period. In addition, the expression of Ngn3, Nkx6.1 and insulin increased in oligosaccharide-treated compared to untreated diabetic rats. Owing to the verified anti-diabetic effects and regenerative potential, isolated oligosaccharide could be considered as the promising drug in the management of diabetes.
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http://dx.doi.org/10.1016/j.carres.2020.107927DOI Listing
March 2020

Impact of plasma concentration of transferrin on targeting capacity of nanoparticles.

Nanoscale 2020 Feb;12(8):4935-4944

Department of Radiology and Precision Health Program, MI 48824, USA.

It is becoming increasingly accepted that various diseases have a capacity to alter the composition of plasma proteins. This alteration in protein composition may consequently change the targeting capacity of nanoparticles (NPs). In this study, the impact of a model targeting ligand's (i.e., Transferrin; Tf) concentration in human plasma on the targeting capacity of gold NPs (Au NPs), pre-conjugated with Tf, is investigated. Our findings demonstrate that the protein corona formation by both healthy and Tf depleted human plasma diminishes the targeting efficacy of Au NPs within human cancer cells despite a preservation of targeting ability by plasma with excess Tf (10-fold). Moreover, the plasma samples obtained from patients with various Tf levels (e.g., thalassemia major, sickle cell anemia, aplastic anemia, and iron deficiency anemia) have affected the accessibility of the targeting Tf in the corona layer and subsequently affected their targeting ability, which emphasizes the critical role of disease-specific protein corona on the efficacy of Au NPs. Ultimately, variations of protein concentration (e.g., due to disease occurrence and progress) in plasma affect its recruiting in corona formation, and in turn, affect the targeting and therapeutic efficacies of Au NPs.
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http://dx.doi.org/10.1039/c9nr08784bDOI Listing
February 2020

Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on Medical Interventions.

Int J Nanomedicine 2020 21;15:363-386. Epub 2020 Jan 21.

Marquette University School of Dentistry, Milwaukee, WI 53201, USA.

The advent of porous materials, in particular zeolitic nanoparticles, has opened up unprecedented putative research avenues in nanomedicine. Zeolites with intracrystal mesopores are low framework density aluminosilicates possessing a regular porous structure along with intricate channels. Their unique physiochemical as well as physiological parameters necessitate a comprehensive overview on their classifications, fabrication platforms, cellular/macromolecular interactions, and eventually their prospective biomedical applications through illustrating the challenges and opportunities in different integrative medical and pharmaceutical fields. More particularly, an update on recent advances in zeolite-accommodated drug delivery and the prevalent challenges regarding these molecular sieves is to be presented. In conclusion, strategies to accelerate the translation of these porous materials from bench to bedside along with common overlooked physiological and pharmacological factors of zeolite nanoparticles are discussed and debated. Furthermore, for zeolite nanoparticles, it is a matter of crucial importance, in terms of biosafety and nanotoxicology, to appreciate the zeolite-bio interface once the zeolite nanoparticles are exposed to the bio-macromolecules in biological media. We specifically shed light on interactions of zeolite nanoparticles with fibrinogen and amyloid beta which had been comprehensively investigated in our recent reports. Given the significance of zeolite nanoparticles' interactions with serum or interstitial proteins conferring them new biological identity, the preliminary approaches for deeper understanding of administration, distribution, metabolism and excretion of zeolite nanoparticles are elucidated.
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http://dx.doi.org/10.2147/IJN.S234573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983480PMC
April 2020

Cell junction proteins: Crossing the glomerular filtration barrier in diabetic nephropathy.

Int J Biol Macromol 2020 Apr 18;148:475-482. Epub 2020 Jan 18.

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

Diabetic nephropathy as a deleterious complication of diabetes mellitus and an important cause of end-stage renal failure is characterized by changes in the molecular and cellular levels. Cell-cell communication via the gap and tight junctions are involved in the pathogenesis of diseases such as diabetes and kidney failure. Studying cell junctions including gap junctions, tight junctions, and anchoring junctions within the nephron can be used as an early sign of diabetic nephropathy. Furthermore, cell junctions may be an upcoming target by pharmacological methods to improve treatments of diabetic nephropathy and pave the way to introduce promising therapeutic strategies based on cell-cell communications effects and its translation into clinical studies for the treatment of diabetic nephropathy.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.168DOI Listing
April 2020

Novel therapeutic strategies for Alzheimer's disease: Implications from cell-based therapy and nanotherapy.

Nanomedicine 2020 02 10;24:102149. Epub 2020 Jan 10.

Department of Anatomy and Cell Biology, McGill University, Montreal, Canada. Electronic address:

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which leads to progressive dysfunction of cognition, memory and learning in elderly people. Common therapeutic agents are not only inadequate to suppress the progression of AD pathogenesis but also produce deleterious side effects; hence, development of alternative therapies is required to specifically suppress complications of AD. The current review provides a commentary on conventional as well as novel therapeutic approaches with an emphasis on stem cell and nano-based therapies for improvement and management of AD pathogenesis. According to our overview of the current literature, AD is a multi-factorial disorder with various pathogenic trajectories; hence, a multifunctional strategy to create effective neuroprotective agents is required to treat this disorder.
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http://dx.doi.org/10.1016/j.nano.2020.102149DOI Listing
February 2020

A novel bio-inspired conductive, biocompatible, and adhesive terpolymer based on polyaniline, polydopamine, and polylactide as scaffolding biomaterial for tissue engineering application.

Int J Biol Macromol 2020 Mar 18;147:1174-1184. Epub 2019 Nov 18.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

A novel electrically conductive nanofibrous scaffold based on polyaniline-co-(polydopamine-grafted-poly(d,l-lactide)) [PANI-co-(PDA-g-PLA)] was fabricated using electrospinning technique and its physicochemical as well as biological characteristics toward bone tissue engineering (TE) were investigated extensively. In detail, PANI-co-PDA was synthesized via a one-step chemical oxidization approach. Then, d,l-lactaide monomer was grafted onto PDA segment using a ring opening polymerization (ROP) to afford PANI-co-(PDA-g-PLA) terpolymer. The successful synthesis of PANI-co-(PDA-g-PLA) terpolymer was confirmed using FTIR spectroscopy as well as TGA analysis. Finally, a solution of the synthesized terpolymer was electrospun to fabricate a conductive nanofibrous scaffold. Some physicochemical features such as mechanical, conductivity, electroactivity, hydrophobicity, and morphology as well as biological characteristics including biocompatibility, biodegradability, as well as enhancing the cells adhesion and proliferation were investigated. According to the above-mentioned experimental results, the fabricated electrospun nanofibers can be considered as a potential scaffold for TE application, mainly due to its proper physicochemical and biological properties.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.10.086DOI Listing
March 2020

Neuroprotective Potential of Curcumin-Loaded Nanostructured Lipid Carrier in an Animal Model of Alzheimer's Disease: Behavioral and Biochemical Evidence.

J Alzheimers Dis 2019 ;69(3):671-686

Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-β (Aβ) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aβ-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4 ng/g-1 h) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur-NLCs in decreasing the hallmarks of Aβ in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aβ-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.
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http://dx.doi.org/10.3233/JAD-190083DOI Listing
September 2020

Bioaerogels: Synthesis approaches, cellular uptake, and the biomedical applications.

Biomed Pharmacother 2019 Mar 9;111:964-975. Epub 2019 Jan 9.

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Aerogels are a class of porous structures with promising physicochemical properties. Among aerogels with various origins, polysaccharide aerogels (e.g., cellulose, chitosan, alginate, starch, agar, and so on) have received more attention. This group of aerogels can be classified as bioaerogels, which are originated from natural, semi-synthetic, and synthetic sources with exceptional biomedical applications. This review focuses on bioaerogels from the viewpoints of synthesis approaches, cellular uptake, toxicity, biodegradability, and the biomedical application perspectives.
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http://dx.doi.org/10.1016/j.biopha.2019.01.014DOI Listing
March 2019

Molecular interaction of fibrinogen with zeolite nanoparticles.

Sci Rep 2019 02 7;9(1):1558. Epub 2019 Feb 7.

Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, United States.

Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPs via strong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of γ chain (γ), located in D-domain, showed the highest level of exposure compared to other sequences/residues.
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http://dx.doi.org/10.1038/s41598-018-37621-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367512PMC
February 2019

Mesoporous silica nanoparticles for therapeutic/diagnostic applications.

Biomed Pharmacother 2019 Jan 6;109:1100-1111. Epub 2018 Nov 6.

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:

Based on unique intrinsic properties of mesoporous silica nanoparticles (MSNs) such as high surface area, large pore size, good biocompatibility and biodegradability, stable aqueous dispersion, they have received much attention in the recent decades for their applications as a promising platform in the biomedicine field. These porous structures possess a pore size ranging from 2 to 50 nm which make them excellent candidates for various biomedical applications. Herein, at first we described the common approaches of cargo loading and release processes from MSNs. Then, the intracellular uptake, safety and cytotoxicity aspects of MSNs are discussed as well. This review also highlights the most recent advances in the biomedical applications of MSNs, including 1) MSNs-based carriers, 2) MSNs as bioimaging agents, 3) MSNs-based biosensors, 4) MSNs as therapeutic agents (photodynamic therapy), 5) MSN based quantum dots, 6) MSNs as platforms for upconverting nanoparticles, and 6) MSNs in tissue engineering.
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http://dx.doi.org/10.1016/j.biopha.2018.10.167DOI Listing
January 2019

Cell penetrating peptides: A concise review with emphasis on biomedical applications.

Biomed Pharmacother 2018 Dec 28;108:1090-1096. Epub 2018 Sep 28.

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of medical Sciences, Kermanshah, Iran. Electronic address:

Introduction: The biological membranes as natural permeable barriers are required for survival and function of living cells. However, these natural barriers could be a major obstacle for the efficient intracellular delivery of therapeutic agents.

Materials And Methods: In recent two decades, the use of peptides as novel carriers for intracellular cargo delivery has been received more attention by introducing the cell penetrating peptides (CPPs). CPPs, protein transduction domains, are an attractive class of short peptide sequences which can translocate across the cell membrane.

Conclusion: Owing to the ability of CPPs to transport across cellular membrane, they can employ as an appropriate carrier for various cargos include nucleic acid, proteins, SiRNA, therapeutic agents, nanoparticles and so on. In this review, we describe the classifications of CPPs, their uptake mechanisms as well as biomedical applications of the CPPs.
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http://dx.doi.org/10.1016/j.biopha.2018.09.097DOI Listing
December 2018

Biomolecular Corona Dictates Aβ Fibrillation Process.

ACS Chem Neurosci 2018 07 30;9(7):1725-1734. Epub 2018 Apr 30.

Pharmacutical Sciences Research Center , Kermanshah University of Medical Sciences , Kermanshah 67145-67346 , Iran.

Amyloid beta (Aβ), which forms toxic oligomers and fibrils in brain tissues of patients with Alzheimer's disease, is broadly used as a model protein to probe the effect of nanoparticles (NPs) on oligomerization and fibrillation processes. However, the majority of the reports in the field have ignored the effect of the biomolecular corona on the fibrillogenesis of the Aβ proteins. The biomolecular corona, which is a layer composed of various types of biomolecules that covers the surface of NPs upon their interaction with biological fluids, determines the biological fates of NPs. Therefore, during in vivo interaction of NPs with Aβ protein, what the Aβ actually "sees" is the human plasma and/or cerebrospinal fluid (CSF) biomolecular-coated NPs rather than the pristine surface of NPs. Here, to mimic the in vivo effects of therapeutic NPs as antifibrillation agents, we probed the effects of a biomolecular corona derived from human CSF and/or plasma on Aβ fibrillation. The results demonstrated that the type of biomolecular corona can dictate the inhibitory or acceleratory effect of NPs on Aβ and Aβ fibrillation processes. More specifically, we found that the plasma biomolecular-corona-coated gold NPs, with sphere and rod shapes, has less inhibitory effect on Aβ fibrillation kinetics compared with CSF biomolecular-corona-coated and pristine NPs. Opposite results were obtained for Aβ peptide, where the pristine NPs accelerated the Aβ fibrillation process, whereas corona-coated ones demonstrated an inhibitory effect. In addition, the CSF biomolecular corona had less inhibitory effect than those obtained from plasma.
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http://dx.doi.org/10.1021/acschemneuro.8b00076DOI Listing
July 2018

Sensing of Alzheimer's Disease and Multiple Sclerosis Using Nano-Bio Interfaces.

J Alzheimers Dis 2017 ;59(4):1187-1202

Department of Nanotechnology and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases.
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http://dx.doi.org/10.3233/JAD-160206DOI Listing
April 2018

Colon Cancer and Specific Ways to Deliver Drugs to the Large Intestine.

Anticancer Agents Med Chem 2017 ;17(10):1317-1327

Institute of Biochemistry and Biophysics, University of Tehran, Tehran. Iran.

Background: It has been postulated that colon cancer is the third cause of cancer death worldwide. Recently, colon-targeted drug delivery systems have been developed for improving systemic drug delivery and treatment of local colon associated diseases. Using such drug delivery systems increases the drug's effectiveness and results in reduced systemic side effects. Drug delivery systems formulated for the colon requires that the triggering of drug release mechanism is designed based on the colon's physiological conditions. However, improving the site specificity and drug release kinetics of colon-targeted drug delivery systems is desired and is currently under active research.

Objective: This review discusses colon cancer along with various colon-targeted drug delivery systems such as pro-drug formation, pH-sensitive polymers, hydrogels, time-dependent release systems, bio-adhesive and nanoparticle systems. The aim is to understand the effect of using colon-targeted drug delivery systems on therapeutic effectiveness of the drug by improving its degradation and bioavailability. Colon targeting holds a great promise as a therapeutic approach but it still requires more innovation.

Conclusion: The distribution of the drugs in the colon suffers from problems related to the pH, retention time, micro-flora, and degrading enzymes of gastrointestinal tract. Moreover, these drug delivery systems are capable of overcoming some of the limitations in common targeting approaches. A precise assessment of such systems needs the use of various assaying protocols in order to characterize their traits and clarify their design rationales.
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http://dx.doi.org/10.2174/1871520617666170213142030DOI Listing
October 2017

Zeolite Nanoparticles Inhibit Aβ-Fibrinogen Interaction and Formation of a Consequent Abnormal Structural Clot.

ACS Appl Mater Interfaces 2016 Nov 1;8(45):30768-30779. Epub 2016 Nov 1.

Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.

EMT-type zeolite nanoparticles (EMT NPs) with particle size of 10-20 nm and external surface area of 200 m/g have shown high selective affinity toward plasma protein (fibrinogen). Besides, the EMT NPs have demonstrated no adverse effect on blood coagulation hemostasis. Therefore, it was envisioned that the EMT NPs could inhibit possible β-amyloid (Aβ)-fibrinogen interactions that result in the formation of structurally abnormal clots, which are resistant to lysis, in cerebral vessels of patients with Alzheimer disease (AD). To evaluate this hypothesis, the clot formation and degradation of Aβ-fibrinogen in the presence and absence of the EMT zeolite NPs were assessed. The results clearly showed that the delay in clot dissolution was significantly reduced in the presence of zeolite NPs. By formation of protein corona, the EMT NPs showed a negligible reduction in their inhibitory strength. Docking of small molecules (Aβ-fibrinogen) introduced a novel potential inhibitory candidate. The zeolite NPs showed similar inhibitory effects on binding of fibrinogen to both Aβ(25-35) and/or Aβ(1-42). This indicates that the inhibitory strength of these NPs is independent of Aβ sequence, and it is suggested that the zeolite NPs adsorb fibrinogen and specifically obstruct their Aβ binding sites. Therefore, the zeolite NPs can be the safe and effective inhibitors in preventing Aβ-fibrinogen interaction and consequent cognitive damage.
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http://dx.doi.org/10.1021/acsami.6b10941DOI Listing
November 2016

Classification of stimuli-responsive polymers as anticancer drug delivery systems.

Drug Deliv 2015 Feb 19;22(2):145-55. Epub 2014 Feb 19.

Institute of Biochemistry and Biophysics, University of Tehran , Tehran , Iran .

Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.
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http://dx.doi.org/10.3109/10717544.2014.887157DOI Listing
February 2015