Publications by authors named "Abbas Salihi"

27 Publications

  • Page 1 of 1

Nanoformulation of Polyphenol Curcumin Enhances Cisplatin-Induced Apoptosis in Drug-Resistant MDA-MB-231 Breast Cancer Cells.

Molecules 2022 May 3;27(9). Epub 2022 May 3.

Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz P.O. Box 5166616471, Iran.

Triple Negative Breast Cancer (TNBC) is the aggressive and lethal type of breast malignancy that develops resistance to current therapies. Combination therapy has proven to be an effective strategy on TNBC. We aimed to study whether the nano-formulation of polyphenolic curcumin (Gemini-Cur) would affect the cisplatin-induced toxicity in MDA-MB-231 breast cancer cells. MDA-MB-231 cells were treated with Gemini-Cur, cisplatin and combination of Gemini-Cur/Cisplatin in a time- and dose-dependent manner. Cell viability was studied by using MTT, fluorescence microscopy and cell cycle assays. The mode of death was also determined by Hoechst staining and annexin V-FITC. Real-time PCR and western blotting were employed to detect the expression of BAX and BCL-2 genes. Our data demonstrated that Gemini-Cur significantly sensitizes cancer cells to cisplatin (combination index ≤ 1) and decreases IC50 values in comparison with Gemini-cur or cisplatin. Further studies confirmed that Gemini-Cur/Cisplatin suppresses cancer cell growth through induction of apoptosis ( < 0.001). In conclusion, the data confirm the synergistic effect of polyphenolic curcumin on cisplatin toxicity and provide attractive strategy to attain its apoptotic effect on TNBC.
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http://dx.doi.org/10.3390/molecules27092917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104165PMC
May 2022

Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.

Mol Cancer 2022 03 3;21(1):64. Epub 2022 Mar 3.

Institute of Human Genetics, Jena University Hospital, Jena, Germany.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) shows the opportunity to treat a diverse array of untreated various genetic and complicated disorders. Therapeutic genome editing processes that target disease-causing genes or mutant genes have been greatly accelerated in recent years as a consequence of improvements in sequence-specific nuclease technology. However, the therapeutic promise of genome editing has yet to be explored entirely, many challenges persist that increase the risk of further mutations. Here, we highlighted the main challenges facing CRISPR/Cas9-based treatments and proposed strategies to overcome these limitations, for further enhancing this revolutionary novel therapeutics to improve long-term treatment outcome human health.
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http://dx.doi.org/10.1186/s12943-021-01487-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892709PMC
March 2022

Cancer Incidence in the Kurdistan Region of Iraq: Results of a Seven-Year Cancer Registration in Erbil and Duhok Governorates.

Asian Pac J Cancer Prev 2022 Feb 1;23(2):601-615. Epub 2022 Feb 1.

Center of Research and Strategic Studies, Lebanese French University, Erbil, Iraq.

Introduction: There are limited published data regarding the recent incidence trends of cancer in Iraqi Kurdistan.

Methods: The present study assessed the epidemiological estimates of cancer incidence, as well providing a projection of future cancer trends in the upcoming decade by analysing the population-based cancer registry between 2013 and 2019, in both the Erbil and Duhok governorates. A retrospective analysis was performed on data retrieved from the Medical Statistics Department at the Ministry of Health, Kurdistan Regional Government (KRG).

Results: The total number of female cancer patients was higher in both governorates, and the total incidence of patients with cancer increased by over 2x between 2013 and 2019 in Erbil and Duhok, from 73 to 174 patients/100,000 individuals for women, and 36 to 85 patients/100,000 individuals for men. Analysis indicated that the percentage of patients with cancer is projected to increase by >2x in the current decade, from 3,457 cases to 4,547 and 4,449 cases in the Erbil governorate; and from 1,365 to 2,633 and 2,737 cases in 2028 based on LSTM and bi-LTSM analysis in the Duhok governorate. Lung cancer (LC) and female breast cancer (BC) were the most prominent types of cancers diagnosed since 2013 in both the Erbil and Duhok governorates.

Conclusion: The striking pattern of trends for both present and future cancer incidence rates require urgent solutions and comprehensive efforts to control risk factors that promote the increasing incidence of cancer in these two KRG governorates.
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http://dx.doi.org/10.31557/APJCP.2022.23.2.601DOI Listing
February 2022

The emerging roles of NGS in clinical oncology and personalized medicine.

Pathol Res Pract 2022 Feb 10;230:153760. Epub 2022 Jan 10.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Next-generation sequencing (NGS) has been increasingly popular in genomics studies over the last decade, as new sequencing technology has been created and improved. Recently, NGS started to be used in clinical oncology to improve cancer therapy through diverse modalities ranging from finding novel and rare cancer mutations, discovering cancer mutation carriers to reaching specific therapeutic approaches known as personalized medicine (PM). PM has the potential to minimize medical expenses by shifting the current traditional medical approach of treating cancer and other diseases to an individualized preventive and predictive approach. Currently, NGS can speed up in the early diagnosis of diseases and discover pharmacogenetic markers that help in personalizing therapies. Despite the tremendous growth in our understanding of genetics, NGS holds the added advantage of providing more comprehensive picture of cancer landscape and uncovering cancer development pathways. In this review, we provided a complete overview of potential NGS applications in scientific and clinical oncology, with a particular emphasis on pharmacogenomics in the direction of precision medicine treatment options.
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http://dx.doi.org/10.1016/j.prp.2022.153760DOI Listing
February 2022

Signaling pathways modulated by miRNAs in breast cancer angiogenesis and new therapeutics.

Pathol Res Pract 2022 Feb 10;230:153764. Epub 2022 Jan 10.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

MicroRNAs (miRNAs) act as oncogenes or tumor suppressors by suppressing the expression of target genes, some of which are engaged in angiogenic signaling pathways directly or indirectly. Tumor development and metastasis are dependent on angiogenesis, and it is the main reason for the poor prognosis of cancer patients. New blood vessels are formed from pre-existing vessels when angiogenesis occurs. Thus, it is essential to develop primary tumors and the spread of cancer to surrounding tissues. MicroRNAs (miRNAs) are small noncoding RNAs involved in various biological processes. They can bind to the 3'-UTR of their target genes and prevent them from expressing. MiRNAs control the activity of endothelial cells (ECs) through altering many biological pathways, which plays a key role in cancer progression and angiogenesis. Recent findings revealed that tumor-derived extracellular vesicles participated directly in the control of tumor angiogenesis by delivering miRNAs to ECs. miRNAs recently show great promise in cancer therapies to inhibit angiogenesis. In this study, we showed the miRNA-regulated signaling pathways in tumor angiogenesis with highlighting the anti-angiogenic therapy response and miRNA delivery methods that have been used to inhibit angiogenesis in both in vivo and in vitro studies.
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http://dx.doi.org/10.1016/j.prp.2022.153764DOI Listing
February 2022

MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets.

Front Mol Biosci 2021 26;8:764025. Epub 2021 Oct 26.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The high incidence of breast cancer (BC) is linked to metastasis, facilitated by tumor angiogenesis. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. There's increasing evidence showed that various miRNAs play a significant role in disease processes; specifically, they are observed and over-expressed in a wide range of diseases linked to the angiogenesis process. However, more studies are required to reach the best findings and identify the link among miRNA expression, angiogenic pathways, and immune response-related genes to find new therapeutic targets. Here, we summarized the recent updates on miRNA signatures and their cellular targets in the development of breast tumor angiogenetic and discussed the strategies associated with miRNA-based therapeutic targets as anti-angiogenic response.
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http://dx.doi.org/10.3389/fmolb.2021.764025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582349PMC
October 2021

The role of oxidative stress and haematological parameters in relapsing-remitting multiple sclerosis in Kurdish population.

Mult Scler Relat Disord 2021 Nov 28;56:103228. Epub 2021 Aug 28.

Department of Surgery, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. Electronic address:

Background: Multiple sclerosis (MS), as a neurodegenerative disorder, exhibits inflammation and oxidative stress hallmarks.

Objective: The research aims to know any disturbances in haematological parameters and antioxidant system of relapsing-remitting multiple sclerosis (RRMS) patients in the Kurdish population.

Methods: A case-control research meeting following the McDonald criterion was conducted on 100 RRMS patients and 100 controls.

Results: Lipid peroxidation products of malondialdehyde (MDA), erythrocyte sedimentation rate (ESR), and total leucocyte counts (TLCs) were increased significantly, but copper (Cu+2) and superoxide dismutase (SOD) were decreased significantly while nitric oxide metabolites (NOx) and lymphocyte were not changed significantly if compared with that of controls.

Conclusion: Findings from our study revealed that some defects were detected in haematological profiles in the Kurdish population and disturbance of immunological parameters. In addition, the utilization of Cu+2 supplement as an effective modality for RRMS patients may be beneficial.
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http://dx.doi.org/10.1016/j.msard.2021.103228DOI Listing
November 2021

Association between the serum concentrations and mutational status of IL-8, IL-27 and VEGF and the expression levels of the hERG potassium channel gene in patients with colorectal cancer.

Oncol Lett 2021 Sep 14;22(3):665. Epub 2021 Jul 14.

Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region 44001, Iraq.

The present study aimed to determine the diagnostic value of the serum levels and mutational status of IL-8, IL-27 and VEGF, and the expression levels of human ether-a-go-go-related gene (hERG) in patients with colorectal cancer (CRC). The serum concentrations were determined using the ELISA technique and genotype variations of IL-8, IL-27 and VEGF were examined using Sanger sequencing, and the expression levels of hERG, which encodes a potassium channel, were determined by quantitative PCR, in blood and tissue samples obtained from 80 patients with CRC and 80 healthy individuals. The results of the present study revealed that the percentage of granulocytes and serum concentrations of carcinoembryonic antigen, IL-8 and IL-27 were significantly increased, whereas the percentage of lymphocytes was decreased in patients with CRC. In total, 31 mutations in three genes (eight mutations in VEGF, 13 mutations in IL-27 and 10 mutations in IL-8) were identified in patients with CRC. The relative mRNA expression levels of hERG were also significantly upregulated in tissue and blood samples of patients with CRC compared with those of healthy individuals. In conclusion, the results of the present study indicated that the increased concentrations and genetic variations of IL-8, IL-27 and VEGF may serve important roles in the development and angiogenic processes of CRC. These changes were concomitant with the upregulation of the expression levels of the potassium channel hERG.
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http://dx.doi.org/10.3892/ol.2021.12926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299013PMC
September 2021

MicroRNA: A signature for cancer progression.

Biomed Pharmacother 2021 Jun 23;138:111528. Epub 2021 Mar 23.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

MicroRNAs (miRNAs) are a group of small non-coding RNAs that post-transcriptionally control expression of genes by targeting mRNAs. miRNA alterations partake in the establishment and progression of different types of human cancer. Consequently, expression profiling of miRNA in human cancers has correlations with cancer detection, staging, progression, and response to therapies. Particularly, amplification, deletion, abnormal pattern of epigenetic factors and the transcriptional factors that mediate regulation of primary miRNA frequently change the landscape of miRNA expression in cancer. Indeed, changes in the quantity and quality of miRNAs are associated with the initiation of cancer, its progression and metastasis. Additionally, miRNA profiling has been used to categorize genes that can affect oncogenic pathways in cancer. Here, we discuss several circulating miRNA signatures, their expression profiles in different types of cancer and their impacts on cellular processes.
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http://dx.doi.org/10.1016/j.biopha.2021.111528DOI Listing
June 2021

In vitro anticancer activity of hydrogen sulfide and nitric oxide alongside nickel nanoparticle and novel mutations in their genes in CRC patients.

Sci Rep 2021 01 28;11(1):2536. Epub 2021 Jan 28.

Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, 44002, Iraq.

This study was carried out to assess the impact of nickel nanoparticles (NiNPs) as well as scorpion venom on colorectal cancer (CRC) cells in the presence and/or absence of 5-fluorouracil (5-FU), hydrogen sulfide (HS), and nitric oxide (NO) donors and to determine alterations in endothelial NO synthase (eNOS) and cystathionine γ-lyase (CSE) enzyme-producing genes in CRC patients. The IC of both HS and NO donors, along with NiNPs, were determined. The CRC cells were treated for 24hrs, and the cytotoxic activities were assessed using the MTT test. Moreover, the apoptosis was determined after 24hrs and 48hrs using TUNEL assay. Furthermore, the mutations in the eNOS gene (intron 4, -786T>C and 894 G>T) and CSE gene (1364GT) were determined using direct sequencing. The IC values for sodium disulfide (NaS) and sodium nitroprusside (SNP) at 24hrs treatment were found to be 5 mM and 10 M, respectively, while the IC value for 5-FU was reached after 5-days of treatment in CRC cell line. Both black and yellow scorpion venoms showed no inhibition of cell proliferation after 24hrs treatment. Furthermore, NaS showed a significant decrease in cell proliferation and an increase in apoptosis. Moreover, a co-treatment of SNP and 5-FU resulted in inhibition of the cytotoxic effect of 5-FU, while a combination treatment of NiNPs with NaS, SNP, and 5-FU caused highly significant cytotoxicity. Direct sequencing reveals new mutations, mainly intronic variation in eNOS gene that has not previously been described in the database. These findings indicate that HS promotes the anticancer efficiency of 5-FU in the presence of NiNPs while NO has antiapoptotic activity in CRC cell lines.
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http://dx.doi.org/10.1038/s41598-021-82244-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843626PMC
January 2021

Cardiac, Hepatic and Renal Dysfunction and IL-18 Polymorphism in Breast, Colorectal, and Prostate Cancer Patients.

Asian Pac J Cancer Prev 2021 Jan 1;22(1):131-137. Epub 2021 Jan 1.

Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq.

Introduction: The present study aimed to determine the alterations in the serum levels of tumor markers used to evaluate cardiac, renal and liver function, and detect the interleukin (IL)-18 rs1946518 polymorphism in breast (BC), colorectal (CRC) and prostate cancer (PCa) patients.

Methods: Blood samples were collected from 65 female BC, 116 CRC, 79 PCa and 88 myocardial infarction (MI) patients, and 110 healthy individuals to determine the concentration of tumor and cardiac markers. Furthermore, the IL-18 rs1946518 polymorphism was assessed using amplification refractory mutation system (ARMS)-PCR.

Results: The serum levels of the tumor markers cancer antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and total prostate-specific antigen (TPSA) were significantly increased in cancer patients compared with healthy controls. Furthermore, the activity of high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase‑myocardial band (CK-MB) was enhanced in MI patients, however, their activity was unchanged in cancer patients. The activity of alkaline phosphatase (ALP), and the serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea were markedly elevated in CRC and PCa patients, respectively, compared with the control group. Although, no significant differences were observed in the -607 C/A polymorphism and allele frequency of IL-18 among BC, CRC patients and healthy individuals, the odds ratio (OR) was 1.75 for both C and A allele in BC patients. Therefore, the -607 C/A polymorphism could be considered as a risk factor for BC.

Conclusion: The aforementioned results suggested that tumor markers could be considered as excellent biomarkers for the early detection of BC, CRC and PCa, whereas the concentration of liver enzymes could serve as an alternative indicator for the diagnosis of CRC and PCa. Additionally, the rs1946518 polymorphism in the IL-18 gene could be considered as a risk factor for the occurrence of BC, CRC and PCa.
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http://dx.doi.org/10.31557/APJCP.2021.22.1.131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184168PMC
January 2021

The vasodilatory mechanism of nitric oxide and hydrogen sulfide in the human mesenteric artery in patients with colorectal cancer.

Exp Ther Med 2021 Mar 15;21(3):214. Epub 2021 Jan 15.

Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region 44001, Iraq.

Recent studies have focused on the role of gasotransmitters in cancer progression and prevention. Therefore, the current study was designed to explore the vasodilator activity of NO and HS in the human mesenteric arteries of patients with colorectal cancer (CRC) via the activation of K channels. A total of two sets of experiments were established for the current investigation. Blood samples from patients with CRC were obtained to detect serum levels of endocan and malondialdehyde (MDA). The role of K channels in mediating the vasodilation of the human mesenteric artery in response to sodium nitroprusside (SNP) and sodium disulfide (NaS) was assessed. The level of serum endocan was indicated to be decreased in patients with CRC compared with healthy individuals, while the level of serum MDA remained unaltered between groups. The arterial rings pre-contracted with norepinephrine were first relaxed by the cumulative addition of increasing concentrations of either SNP (30 nM-30 µM) or (1-6 mM). Maximal relaxation rates were then calculated at 15 min intervals for 60 min. Pre-incubation of arterial rings for 20 min with individual K channel blockers was indicated to significantly reduce SNP- and NaS-induced relaxation at different time points. Pre-treatment of L-nitro-arginine methyl ester did not alter vasodilation that was induced by NaS. Furthermore, vasodilation of the CRC mesenteric artery was not altered by the synergistic application of SNP and NaS, while pre-incubation of arterial rings with D,L-propargylglycine significantly enhanced vasodilation induced by SNP. These results indicated that endothelial dysfunction and oxidative stress do not serve roles in the pathogenesis of CRC. The dilatory mechanisms of NO and HS in mesenteric arteries of patients with CRC were K channel- and time-dependent, and the activity of cystathionine γ-lyase enzyme inhibited the ability of exogenous NO in vasodilation processes.
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http://dx.doi.org/10.3892/etm.2021.9646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818576PMC
March 2021

Prevalence of the prothrombin G20210A mutation among ischemic stroke patients.

J Cardiovasc Thorac Res 2020 3;12(3):227-230. Epub 2020 Sep 3.

Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Iraq.

Ischemic stroke is characterized as a sudden neurological deficit attributed to an acute focal injury of the central nervous system by a vascular cause. This study was performed to determine the frequency of G20210A mutation in the prothrombin gene and its effectiveness on the incidence of ischemic stroke in the Erbil city of Kurdistan region, Iraq. A total of 50 patients with ischemic stroke was analyzed for the detection of prothrombin gene mutation (G20210A), using polymerase chain reaction (PCR), Restriction fragment length polymorphism (RFLP) with Hind III restriction enzyme. We observed no evidence of an association between ischemic stroke and G20210A mutation in the prothrombin gene in this region. Our finding demonstrates that prothrombotic gene variant seems not to be linked to the incidence of ischemic stroke in Erbil region.
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http://dx.doi.org/10.34172/jcvtr.2020.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581837PMC
September 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

Combined chemo-magnetic field-photothermal breast cancer therapy based on porous magnetite nanospheres.

Sci Rep 2020 04 3;10(1):5925. Epub 2020 Apr 3.

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

The efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance.
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http://dx.doi.org/10.1038/s41598-020-62429-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125194PMC
April 2020

Plasmonic and chiroplasmonic nanobiosensors based on gold nanoparticles.

Talanta 2020 May 30;212:120782. Epub 2020 Jan 30.

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

Development of optical nanobiosensors has emerged as one of the most important bioresearch areas of interest over the past decades especially in the modern innovations in the design and utilization of sensing platforms. The application of nanobiosensors has been accelerated with the introduction of plasmonic NPs, which overcome the most of the limitations in the case of conventional optical nanobiosensors. Since the plasmonic AuNPs-based nanobiosensors provide high potential achievements to develop promising platforms in fully integrated multiplex assays, some well-developed investigations are clearly required to improve the current technologies and integration of multiple signal inputs. Therefore, in this literature, we summarized the performance and achievements of optical nanobiosensors according to plasmonic rules of AuNPs, including SPR, LSPR, SERS and chiroptical phenomena. Also, we investigated the effects of the physicochemical properties of AuNPs such as size, shape, composition, and assembly on the plasmonic signal propagation in AuNPs-based nanobiosensors. Moreover, we presented an overview on the current state of plasmonic AuNPs-based nanobiosensors in the biomedical activities. Besides, this paper looks at the current and future challenges and opportunities of ongoing efforts to achieve the potential applications of AuNPs-based optical plasmonic nanobiosensors in integration with other nanomaterials. Taken together, the main focus of this paper is to provide some applicable information to develop current methodologies in fabrication of potential AuNPs-based nanobiosensors for detection of a wide range of analytes.
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http://dx.doi.org/10.1016/j.talanta.2020.120782DOI Listing
May 2020

Gold nanozyme: Biosensing and therapeutic activities.

Mater Sci Eng C Mater Biol Appl 2020 Mar 12;108:110422. Epub 2019 Nov 12.

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

The utilization of AuNPs in therapeutic applications has been accelerated by discovering their catalytic activity consistent with the activity of natural enzymes. However, to reduce unwanted activities, it is imperative to fully understand their catalytic mechanisms to increase efficiency and safety. Therefore, along with other reports, we aimed to classify the enzymatic activity of Au nanozymes based on recent advance in their applications in biosensing and therapeutic activities. The results of the reported experiments indicate that the Au nanozymes can be used in biosensing of a wide range of agents such as molecule (HO and glucose), ions, nucleic acids, proteins, cells, and pathogens. Furthermore, they can be used as potential candidates in inhibition of neurodegenerative diseases, cancer therapy, and antibacterial activities. Biosensing and therapeutic activities are generally based on colorimetric assays and the controlling the ROS level in the targeted cells, respectively. Finally, a brief explanation of the current challenges of the Au nanozymes in biomedical approaches was discussed. Indeed, this review holds a great promise in understanding the Au nanozymes properties and their development in biotechnology, medicine, and related industries.
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http://dx.doi.org/10.1016/j.msec.2019.110422DOI Listing
March 2020

Enzyme immobilization onto the nanomaterials: Application in enzyme stability and prodrug-activated cancer therapy.

Int J Biol Macromol 2020 Jan 10;143:665-676. Epub 2019 Dec 10.

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

Nanoparticles (NPs) have been widely used for immobilization of wide ranges of enzymes. However, the stabilization of enzymes on NPs is a major challenge, crucial for regulating enzymatic activity and their medical applications. To overcome these challenges, it is necessary to explore how enzymes attach to nanomaterials and their properties are affected by such interactions. In this review we present an overview on the different strategies of the enzyme immobilization into the NPs and their corresponding stability against temperature and pH. The effects of surface charge, particle size, morphology, and aggregation of NPs on the stability of immobilized enzymes were summarized. The activity of immobilized enzyme into the NPs was reviewed to disclose more detail regarding the interaction of biomolecules with NPs. The combination of enzyme immobilization with prodrugs was also reviewed as a promising approach for biomedical application of enzyme in cancer therapy. Finally, the current challenges and future applications of NPs in enzyme immobilization and the utilization of immobilized enzyme toward prodrug activation in cytoplasm of cancer cells were presented. In conclusion, this review may pave the way for providing a perspective on development to the industrial and clinical translation of immobilized enzymes.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.12.064DOI Listing
January 2020

Vitamin K1 As A Potential Molecule For Reducing Single-Walled Carbon Nanotubes-Stimulated α-Synuclein Structural Changes And Cytotoxicity.

Int J Nanomedicine 2019 24;14:8433-8444. Epub 2019 Oct 24.

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

Aims: Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays.

Methods: Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SH-SY5Y cells was also carried out by MTT, LDH, and caspase-3 assays.

Results: Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of α- syn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of α- syn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on α- syn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of α- syn induced by SWCNT. Cellular data exhibited that the cytotoxicity of α- syn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1.

Conclusion: It may be concluded that vitamin K1 decreases the propensity of α- syn aggregation in the presence of SWCNTs and induction of cytotoxicity.
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http://dx.doi.org/10.2147/IJN.S223182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818677PMC
January 2020

Silymarin-albumin nanoplex: Preparation and its potential application as an antioxidant in nervous system in vitro and in vivo.

Int J Pharm 2019 Dec 9;572:118824. Epub 2019 Nov 9.

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

In this study, we formulated silymarin-HSA nanoplex and assayed its ability to reduce LPS-induced toxicity in vitro and in vivo. Silymarin molecules were encapsulated into HSA nanoplex and the loading efficiency and characterization of fabricated nanoplex were performed by using HPLC, TEM, SEM, DLS, FTIR analysis, and theoretical studies. Afterwards, their protective effect against LPS (20 µg/ml) -induced toxicity in SH-SY5Y cells was investigated by MTT, ROS, and apoptosis assays. For in vivo experiments, rats were pre-treated with either silymarin or silymarin -HSA nanoplex (200 mg/kg) orally for 3 days and at third day received LPS by IP at a dose of 0.5 mg/kg, 150 min before scarification followed by SOD and CAT activity assay. The formulation of silymarin-HSA nanoplex showed a spherical shape with an average diameter between 50 nm and 150 nm, hydrodynamic radius of 188.3 nm, zeta potential of -26.6 mV, and a drug loading of 97.3%. In LPS-treated cells, pretreatments with silymarin-HSA noncomplex recovered the cell viability and decreased the ROS level and corresponding apoptosis more significantly than free silymarin. In rats, it was also depicted that, silymarin-HSA noncomplex can increase the SOD and CAT activity in brain tissue at LPS-triggered oxidative stress model more significantly than the free counterpart. Therefore, nanoformulation of silymarin improved its capability to reduce LPS-induced oxidative stress by restoring cell viability and elevation of SOD and CAT activity in vitro and in vivo, respectively. In conclusion, formulation of silymarin may hold a great promise in the development of antioxidant agents.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118824DOI Listing
December 2019

Cerium oxide NPs mitigate the amyloid formation of α-synuclein and associated cytotoxicity.

Int J Nanomedicine 2019 29;14:6989-7000. Epub 2019 Aug 29.

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

Aim: Among therapeutic proposals for amyloid-associated disorders, special attention has been given to the exploitation of nanoparticles (NPs) as promising agents against aggregation.

Methods: In this paper, the inhibitory effect of cerium oxide (CeO) NPs against α-synuclein (α-syn) amyloid formation was explored by different methods such as Thioflavin T (ThT) and 8-anilinonaphthalene-1-sulfonic acid (ANS) fluorescence spectroscopy, Congo red adsorption assay, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and bioinformatical approaches. Also, the cytotoxicity of α-syn amyloid either alone or with CeO NPs against neuron-like cells (SH-SY5Y) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and quantitative real-time polymerase chain reaction (Bax and Bcl-2 gene expression) assays.

Results: ThT and ANS fluorescence assays indicated that CeO NPs inhibit the formation of aggregated species and hydrophobic patches of α-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO NPs reduce the formation of amyloid species and β-sheets structures of α-syn molecules, respectively. TEM investigation also confirmed that CeO NPs limited the formation of well-defined fibrillary structures of α-syn molecules. Molecular docking and dynamic studies revealed that CeO NPs could bind with different affinities to α-syn monomer and amyloid species and fibrillar structure of α-syn is disaggregated in the presence of CeO NPs. Moreover, cellular assays depicted that CeO NPs mitigate the cell mortality, apoptosis, and the ratio of Bax/Bcl-2 gene expression associated with α-syn amyloids.

Conclusion: It may be concluded that CeO NPs can be used as therapeutic agents to reduce the aggregation of proteins and mitigate the occurrence of neurodegenerative diseases.
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http://dx.doi.org/10.2147/IJN.S220380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718255PMC
January 2020

Gold nanomaterials as key suppliers in biological and chemical sensing, catalysis, and medicine.

Biochim Biophys Acta Gen Subj 2020 01 14;1864(1):129435. Epub 2019 Sep 14.

Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, United States.

Background: Gold nanoparticles (AuNPs) with unique physicochemical properties have received a great deal of interest in the field of biological, chemical and biomedical implementations. Despite the widespread use of AuNPs in chemical and biological sensing, catalysis, imaging and diagnosis, and more recently in therapy, no comprehensive summary has been provided to explain how AuNPs could aid in developing improved sensing and catalysts systems as well as medical settings.

Scope Of Review: The chemistry of Au-based nanosystems was followed by reviewing different applications of Au nanomaterials in biological and chemical sensing, catalysis, imaging and diagnosis by a number of approaches, and finally synergistic combination therapy of different cancers. Afterwards, the clinical impacts of AuNPs, future application of AuNPs, and opportunities and challenges of AuNPs application were also discussed.

Major Conclusions: AuNPs show exclusive colloidal stability and are considered as ideal candidates for colorimetric detection, catalysis, imaging, and photothermal transducers, because their physicochemical properties can be tuned by adjusting their structural dimensions achieved by the different manufacturing methods.

General Significance: This review provides some details about using AuNPs in sensing and catalysis applications as well as promising theranostic nanoplatforms for cancer imaging and diagnosis, and sensitive, non-invasive, and synergistic methods for cancer treatment in an almost comprehensive manner.
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http://dx.doi.org/10.1016/j.bbagen.2019.129435DOI Listing
January 2020

The effects of nickel oxide nanoparticles on structural changes, heme degradation, aggregation of hemoglobin and expression of apoptotic genes in lymphocytes.

J Biomol Struct Dyn 2020 Aug 12;38(12):3676-3686. Epub 2019 Sep 12.

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

Nickel oxide nanoparticles (NiO NPs) have received great interests in medical and biotechnological applications. However, their adverse impacts against biological systems have not been well-explored. Herein, the influence of NiO NPs on structural changes, heme degradation and aggregation of hemoglobin (Hb) was evaluated by UV-visible (Vis) spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM), and molecular modeling investigations. Also, the morphological changes and expression of Bax/Bcl-2 mRNA in human lymphocyte cell exposed to NiO NPs were assayed by DAPI staining and quantitative real-time PCR (qPCR), respectively. The UV-Vis study depicted that NiO NPs resulted in the displacement of aromatic residues and heme groups and production of the pro-aggregatory species. Intrinsic and Thioflavin T (ThT) fluorescence studies revealed that NiO NPs resulted in heme degradation and amorphous aggregation of Hb, respectively, which the latter result was also confirmed by TEM study. Moreover, far UV-CD study depicted that NiO NPs lead to substantial secondary structural changes of Hb. Furthermore, near UV-CD displayed that NiO NPs cause quaternary conformational changes of Hb as well as heme displacement. Molecular modelling study also approved that NiO NPs resulted in structural alterations of Hb and heme deformation. Moreover, morphological and genotoxicity assays revealed that the DNA fragmentation and expression ratio of Bax/Bcl-2 mRNA increased in lymphocyte cells treated with NiO NPs for 24hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limited.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1662850DOI Listing
August 2020

α-synuclein interaction with zero-valent iron nanoparticles accelerates structural rearrangement into amyloid-susceptible structure with increased cytotoxic tendency.

Int J Nanomedicine 2019 27;14:4637-4648. Epub 2019 Jun 27.

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

Aim: It has been indicated that NPs may change the amyloidogenic steps of proteins and relevant cytotoxicity. Therefore, this report assigned to explore the impact of ZVFe NPs on the amyloidogenicity and cytotoxicity of α-synuclein as one of the many known amyloid proteins.

Methods: The characterization of α-synuclein at amyloidogenic condition either alone or with ZVFe NPs was carried out by fluorescence, CD, UV-visible spectroscopic methods, TEM study, docking, and molecular modeling. The cytotoxicity assay of α-synuclein amyloid in the absence and presence of ZVFe NPs was also done by MTT, LDH, and flow cytometry analysis.

Results: ThT fluorescence spectroscopy revealed that ZVFe NPs shorten the lag phase and accelerate the fibrillation rate of α-synuclein. Nile red and intrinsic fluorescence spectroscopy, CD, Congo red adsorption, and TEM studies indicated that ZVFe NP increased the propensity of α-synuclein into the amyloid fibrillation. Molecular docking study revealed that hydrophilic residues, such as Ser-9 and Lys-12 provide proper sites for hydrogen bonding and electrostatic interactions with adsorbed water molecules on ZVFe NPs, respectively. Molecular dynamics study determined that the interacted protein shifted from a natively discorded conformation toward a more packed structure. Cellular assay displayed that the cytotoxicity of α-synuclein amyloid against SH-SY5Y cells in the presence of ZVFe NPs is greater than the results obtained without ZVFe NPs.

Conclusion: In conclusion, the existence of ZVFe NPs promotes α-synuclein fibrillation at amyloidogenic conditions by forming a potential template for nucleation, the growth of α-synuclein fibrillation and induced cytotoxicity.
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http://dx.doi.org/10.2147/IJN.S212387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602305PMC
October 2019

The interaction of silica nanoparticles with catalase and human mesenchymal stem cells: biophysical, theoretical and cellular studies.

Int J Nanomedicine 2019 16;14:5355-5368. Epub 2019 Jul 16.

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

Aim: Nanoparticles (NPs) have been receiving potential interests in protein delivery and cell therapy. As a matter of fact, NPs may be used as great candidates in promoting cell therapy by catalase (CAT) delivery into high oxidative stress tissues. However, for using NPs like SiO as carriers, the interaction of NPs with proteins and mesenchymal stem cells (MSCs) should be explored in advance.

Methods: In the present study, the interaction of SiO NPs with CAT and human MSCs (hMSCs) was explored by various spectroscopic methods (fluorescence, circular dichroism (CD), UV-visible), molecular docking and dynamics studies, and cellular (MTT, cellular morphology, cellular uptake, lactate dehydrogenase, ROS, caspase-3, flow cytometry) assays.

Results: Fluorescence study displayed that both dynamic and static quenching mechanisms and hydrophobic interactions are involved in the spontaneous interaction of SiO NPs with CAT. CD spectra indicated that native structure of CAT remains stable after interaction with SiO NPs. UV-visible study also revealed that the kinetic parameters of CAT such as , and enzyme efficiency were not changed after the addition of SiO NPs. Molecular docking and dynamics studies showed that Si and SiO clusters interact with hydrophobic residues of CAT and SiO cluster causes minor changes in the CAT structure at a total simulation time of 200 ps. Cellular assays depicted that SiO NPs induce significant cell mortality, change in cellular morphology, cellular internalization, ROS elevation, and apoptosis in hMSCs at higher concentration than 100 µg/mL (170 µM).

Conclusion: The current results suggest that low concentrations of SiO NPs induce no substantial change or mortality against CAT and hMSCs, and potentially useful carriers in CAT delivery to hMSC.
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http://dx.doi.org/10.2147/IJN.S210136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643057PMC
October 2019

The effect of aluminum oxide on red blood cell integrity and hemoglobin structure at nanoscale.

Int J Biol Macromol 2019 Oct 25;138:800-809. Epub 2019 Jul 25.

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

Herein, we explored the interaction of AlO NPs with RBCs and Hb to determine the effect of AlO NPs on hemolytic activity and Hb denaturation. The percentage of hemolysis of extracts and direct contact assays triggered by AlO NPs was calculated by determining supernatant Hb concentration at 540 nm. Far-UV CD and Trp/ANS/acrylamide fluorescence spectroscopic methods were used to determine the structural changes of Hb upon interaction with AlO NPs. Theoretical studies were carried out to display the residues involved in the binding site of Hb with AlO nanocluster as well as the structural changes of Hb after interaction. The results showed that the percentage of hemolysis of extract and direct contact assays induced by AlO NPs were 1.16 and 0.46, respectively. Fluorescence spectroscopy revealed that AlO NPs alter the quaternary structure of the protein; however, CD spectroscopy indicated that the secondary structure of Hb remains almost unchanged. Theoretical study displayed that AlO nanocluster interacts with different residues of protein, and Hb tends to be destabilized at the binding site with nanocluster. This study may be significant in exploring the toxicity profile of AlO NPs for their in vivo implementations.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.07.154DOI Listing
October 2019

Strategies of enzyme immobilization on nanomatrix supports and their intracellular delivery.

J Biomol Struct Dyn 2020 Jun 22;38(9):2746-2762. Epub 2019 Jul 22.

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

Enzymes are one of the foundations and regulators for all major biological activities in living bodies. Hence, enormous efforts have been made for enhancing the efficiency of enzymes under different conditions. The use of nanomaterials as novel carriers for enzyme delivery and regulating the activities of enzymes has stimulated significant interests in the field of nano-biotechnology for biomedical applications. Since, all types of nanoparticles (NPs) offer large surface to volume ratios, the use of NPs as enzyme carriers affect the structure, performance, loading efficiency, and the reaction kinetics of enzymes. Hence, the immobilization of enzymes on nanomatrices can be used as a useful approach for direct delivery of therapeutic enzymes to the targeted sites. In other words, NPs can be used as advanced enzyme delivery nanocarriers. In this paper, we present an overview of different binding of enzymes to the nanomaterials as well as different types of nanomatrix supports for immobilization of enzymes. Afterwards, the enzyme immobilization on nanomaterials as a potential system for enzyme delivery has been discussed. Finally, the challenges associated with the enzyme delivery using nano matrices and their future perspective have been discussed.Communicated by Ramasamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1643787DOI Listing
June 2020
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