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1.
Arab J Chem ; 14(10): 103353, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34909059

RESUMO

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2's proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

2.
Int J Biol Macromol ; 185: 813-820, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34186122

RESUMO

The stability of IFN-γ as a therapeutic protein can play a key role on its anticancer effects. Herein, we explored the thermodynamic parameters and conformational stability of IFN-γ in the presence of calycosin, the main active compound of Radix astragali, by different biophysical and theoretical analysis. Afterwards, the improved anticancer effects of IFN-γ-calycosin interaction relative to IFN-γ alone were assessed on hepatocellular carcinoma (HepG2) cell line by MTT and caspase assays. ITC data indicated that upon interaction of calycosin with IFN-γ the binding and thermodynamic parameters were as follows: Kd = 1.9 µM, ΔG° = -32.45 kJ/mol, ΔH° = -11.91 kJ/mol, and TΔS° = 20.54 kJ/mol. ANS/synchronous fluorescence, CD and UV-Vis spectroscopy studies indicated that the interaction between calycosin and IFN-γ caused the folding of the IFN-γ backbone in to a more packed structure with enhanced α-helix content and higher melting temperature (Tm) value. The spectroscopic outcomes were then verified by molecular docking and molecular dynamic analysis. It was also shown that after incubation of the IFN-γ samples at 50 °C for 60 min in the presence of calycosin (5 µM), the IFN-γ-calycosin system showed a significant antiproliferative effects against hepatocellular carcinoma (HepG2) cells through caspase-9/3 activation and this anticancer effect was more pronounced than free IFN-γ. This data may provide useful information about the development of IFN-γ-based therapeutic platforms.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Interferon gama/farmacologia , Isoflavonas/química , Neoplasias Hepáticas/metabolismo , Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Interferon gama/química , Neoplasias Hepáticas/tratamento farmacológico , Dobramento de Proteína/efeitos dos fármacos , Termodinâmica
3.
Mater Sci Eng C Mater Biol Appl ; 119: 111649, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321685

RESUMO

The interaction of nanoparticles with protein and cells may provide important information regarding their biomedical implementations. Herein, after synthesis of tin oxide (SnO2) nanoparticles by hydrothermal method, their interaction with human serum albumin (HSA) was evaluated by multispectroscopic and molecular docking (MD) approaches. Furthermore, the selective antiproliferative impact of SnO2 nanoparticles against leukemia K562 cells was assessed by different cellular assays, whereas lymphocytes were used as control cells. TEM, DLS, zeta potential and XRD techniques showed that crystalline SnO2 nanoparticles have a size of less than 50 nm with a good colloidal stability. Fluorescence and CD spectroscopy analysis indicated that the HSA undergoes some slight conformational changes after interaction with SnO2 nanoparticles, whereas the secondary structure of HSA remains intact. Moreover, MD outcomes revealed that the charged residues of HSA preferentially bind to SnO2 nanoclusters in the binding pocket. Antiproliferative examinations displayed that SnO2 nanoparticles can selectively cause the mortality of K562 cells through induction of cell membrane leakage, activation of caspase-9, -8, -3, down regulation of Bcl-2 mRNA, the elevation of ROS level, S phase arrest, and apoptosis. In conclusion, this data may indicate that SnO2 nanoparticles can be used as promising particles to be integrated into therapeutic platforms.


Assuntos
Nanopartículas , Compostos de Estanho , Humanos , Células K562 , Simulação de Acoplamento Molecular
4.
Int J Nanomedicine ; 15: 4607-4623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636621

RESUMO

AIM: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects. METHODS: Herein, the interaction of as-synthesized Co3O4 NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co3O4 NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co3O4 NPs against three pathogenic bacteria were disclosed by antibacterial assays. RESULTS: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co3O4 NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of -33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co3O4 NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co3O4 NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co3O4 NPs can stimulate a promising antibacterial effect against pathogenic bacteria. CONCLUSION: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Cobalto/química , Cobalto/farmacologia , Nanopartículas Metálicas/química , Óxidos/química , Óxidos/farmacologia , Albumina Sérica Humana/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobalto/metabolismo , Escherichia coli/efeitos dos fármacos , Humanos , Células K562 , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Óxidos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Albumina Sérica Humana/química , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
5.
Talanta ; 212: 120782, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32113545

RESUMO

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.

6.
J Biomol Struct Dyn ; 38(12): 3676-3686, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31476976

RESUMO

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 24 hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limited.Communicated by Ramaswamy H. Sarma.


Assuntos
Apoptose , Linfócitos , Nanopartículas Metálicas/toxicidade , Níquel/toxicidade , Heme , Hemoglobinas , Humanos
7.
J Biomol Struct Dyn ; 38(10): 2945-2954, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31354071

RESUMO

Studies on the anti-cancer effects of nanomaterials are a very important step in the clinical practice and treatment of cancerous tissues. Since IONPs have a high potential for cancer treatment, their anti-cancer properties can help us to resolve some of the therapeutic problems. For this purpose, in addition to synthesizing two types of IONPs including MN and MHN, Lf coating was used to increase their anti-cancer activity. MN and MHN were synthesized by hydrothermal and thermal methods, respectively, and their physicochemical properties were examined by SEM, zeta-potential, DLS, FTIR, TGA, and magnetism saturation. Molecular modelling was also done to model two steps of functionalization on the IONPs surface. In order to prove the biological activity of fabricated NPs in vitro, experimental assays of NP cytotoxicity were performed on breast cancerous cells (4T1) by MTT and ROS assays. It was found that the MN and MHN have a diameter around 24 and 33 nm, respectively. Also, the hydrodynamic radius of MN and MHN coated with Lf were 30 and 38 nm, and their zeta potential values at pH = 7.5 were -5.3 and -4.2 mV, respectively. Besides, the results of TGA, magnetism saturation and FTIR showed that Lf was successfully loaded onto NPs. Molecular modelling investigation depicted that dimethylamine moiety of the linker provides an intense reactive region for non-bonding linkages with Lf molecules. Cellular studies exhibited that Lf increased the toxicity of NPs and synthesized Lf-MNs provide the highest potency both on mortality and ROS level. This research may provide promising data for development of potential anticancer agents.Communicated by Ramaswamy H. Sarma.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Compostos Férricos , Lactoferrina , Tamanho da Partícula
8.
Int J Pharm ; 572: 118824, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715345

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Albumina Sérica Humana/química , Silimarina/farmacologia , Animais , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Lipopolissacarídeos/toxicidade , Masculino , Neuroblastoma/patologia , Tamanho da Partícula , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Silimarina/administração & dosagem
9.
Int J Nanomedicine ; 14: 8433-8444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749617

RESUMO

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.


Assuntos
Nanotubos de Carbono/química , Vitamina K 1/farmacologia , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Adsorção , Benzotiazóis/metabolismo , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Vermelho Congo , Humanos , L-Lactato Desidrogenase/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Nanotubos de Carbono/ultraestrutura , Espectrometria de Fluorescência
10.
ACS Omega ; 4(13): 15323-15336, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31572831

RESUMO

A novel ultrasensitive and simple amplified immunosensing strategy is designed based on a surface-enhanced fluorescence (SEF) nanohybrid made from covalently conjugated thionine-gold nanoparticles (GNP-Th), as a novel amplified fluorescence label, and magnetic nanoparticles (MNPs), as a biological carrier, used for hepatitis B virus surface antigen (HBsAg) detection. This immunosensing strategy operates on the basis of the capture and then release of the amplified fluorescence label. Capturing of the antiHBs-antibody (Ab)-modified GNP-thionine hybrid (GNP-Th-Ab) is carried out through the formation of a two-dimensional (sandwich) probe between this amplified label and antiHBs-antibody-modified magnetic nanoparticles (MNP-Ab), in the presence of a target antigen and using an external magnetic force. Afterward, releasing of the captured fluorescence label is performed using a protease enzyme (pepsin) by a digestion mechanism of grafted antibodies on the GNP-thionine hybrid. As a result of antibody digestion, the amplified fluorescent hybrids (labels) are released into the solution. To understand the mechanism of enhanced fluorescence, the nature of the interaction between thionine and gold nanoparticles is studied using the B3LYP density functional method. In such a methodology, several new mechanisms and structures are used simultaneously, including a SEF-based metal nanoparticle-organic dye hybrid, dual signal amplification in a two-dimensional probe between the GNP-thionine hybrid and MNPs, and a novel releasing method using protease enzymes. These factors improve the sensitivity and speed, along with the simplicity of the procedure. Under optimal conditions, the fluorescence signal increases with the increment of HBs antigen concentration in the linear dynamic range of 4.6 × 10-9 to 0.012 ng/mL with a detection limit (LOD) of 4.6 × 10-9 ng/mL. The proposed immunosensor has great potential in developing ultrasensitive and rapid diagnostic platforms.

11.
J Control Release ; 311-312: 170-189, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31472191

RESUMO

Over the past two decades, the development of plasmonic nanoparticle (NPs), especially gold (Au) NPs, is being pursued more seriously in the medical fields such as imaging, drug delivery, and theranostic systems. However, there is no comprehensive review on the effect of the physical and chemical parameters of AuNPs on their plasmonic properties as well as the use of these unique characteristic in medical activities such as imaging and therapeutics. Therefore, in this literature the surface plasmon resonance (SPR) modeling of AuNPs was accurately captured toward precision medicine. Indeed, we investigated the importance of plasmonic properties of AuNPs in optical manipulation, imaging, drug delivery, and photothermal therapy (PTT) of cancerous cells based on their physicochemical properties. Finally, some challenges regarding the commercialization of AuNPs in future medicine such as, cytotoxicity, lack of standards for medical applications, high cost, and time-consuming process were discussed.


Assuntos
Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Animais , Diagnóstico por Imagem , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fenômenos Ópticos , Fototerapia
12.
Int J Nanomedicine ; 14: 5355-5368, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409992

RESUMO

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 SiO2 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 SiO2 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 SiO2 NPs with CAT. CD spectra indicated that native structure of CAT remains stable after interaction with SiO2 NPs. UV-visible study also revealed that the kinetic parameters of CAT such as Km, Vmax, Kcat, and enzyme efficiency were not changed after the addition of SiO2 NPs. Molecular docking and dynamics studies showed that Si and SiO2 clusters interact with hydrophobic residues of CAT and SiO2 cluster causes minor changes in the CAT structure at a total simulation time of 200 ps. Cellular assays depicted that SiO2 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 SiO2 NPs induce no substantial change or mortality against CAT and hMSCs, and potentially useful carriers in CAT delivery to hMSC.


Assuntos
Fenômenos Biofísicos , Células-Tronco Mesenquimais/citologia , Modelos Teóricos , Nanopartículas/química , Dióxido de Silício/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Catalase/metabolismo , Forma Celular/efeitos dos fármacos , Dicroísmo Circular , Endocitose/efeitos dos fármacos , Humanos , Cinética , L-Lactato Desidrogenase/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Fluorescência , Termodinâmica
13.
Int J Nanomedicine ; 14: 4637-4648, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417259

RESUMO

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.


Assuntos
Amiloide/metabolismo , Ferro/química , Nanopartículas Metálicas/química , alfa-Sinucleína/metabolismo , Amiloide/química , Benzotiazóis/química , Morte Celular , Linhagem Celular Tumoral , Vermelho Congo/química , Humanos , Cinética , L-Lactato Desidrogenase/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Oxazinas/química , Agregados Proteicos , Estrutura Secundária de Proteína , Espectrometria de Fluorescência , Tirosina/química , alfa-Sinucleína/química , alfa-Sinucleína/ultraestrutura
14.
Int J Biol Macromol ; 138: 800-809, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351960

RESUMO

Herein, we explored the interaction of Al2O3 NPs with RBCs and Hb to determine the effect of Al2O3 NPs on hemolytic activity and Hb denaturation. The percentage of hemolysis of extracts and direct contact assays triggered by Al2O3 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 Al2O3 NPs. Theoretical studies were carried out to display the residues involved in the binding site of Hb with Al2O3 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 Al2O3 NPs were 1.16 and 0.46, respectively. Fluorescence spectroscopy revealed that Al2O3 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 Al2O3 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 Al2O3 NPs for their in vivo implementations.


Assuntos
Óxido de Alumínio/química , Óxido de Alumínio/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemoglobinas/química , Conformação Proteica/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Modelos Moleculares , Conformação Molecular , Nanopartículas/química , Nanopartículas/ultraestrutura , Análise Espectral
15.
Int J Nanomedicine ; 14: 901-911, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774341

RESUMO

Background: Nanoparticles (NPs) when injected into the body can reach target tissues like nervous system and interact with tau proteins and neurons. This can trigger conformational changes of tau and may affect NP toxicity. Methods: In this study, we used several biophysical techniques (extrinsic and intrinsic fluorescence spectroscopy, circular dichroism (CD) spectroscopy, ultraviolet (UV)-visible spectroscopy), transmission electron microscopy (TEM) investigations, molecular docking and molecular dynamics studies, and cellular assays [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry) to reveal how structural changes of tau protein can change the cytotoxicity of titanium dioxide (TiO2) NPs against neuron-like cells (SH-SY5Y) cells. Results: It was shown that TiO2 NPs result in hydrophilic interactions, secondary and tertiary structural changes, and the formation of amorphous tau aggregates. Conformational changes of tau increased the induced cytotoxicity by TiO2 NPs. These data revealed that the denatured adsorbed protein on the NP surface may enhance NP cytotoxicity. Conclusion: Therefore, this study provides useful insights on the NP-protein interactions and discusses how the protein corona can increase cytotoxicity to determine the efficacy of targeted delivery of nanosystems.


Assuntos
Fenômenos Biofísicos , Nanopartículas/química , Agregados Proteicos , Titânio/química , Proteínas tau/química , Naftalenossulfonato de Anilina/química , Apoptose , Benzotiazóis/química , Linhagem Celular Tumoral , Dicroísmo Circular , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Nanopartículas/ultraestrutura , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Triptofano/química
16.
Int J Biol Macromol ; 127: 330-339, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30654034

RESUMO

Herein, the thermodynamic parameters of tau upon interaction with NiO NPs were determined by fluorescence spectroscopy. Also, molecular docking studies were run to explore the binding affinities of NiO NPs clusters with different sizes of 30 Šand 50 Štoward tau. Also, cytotoxic activity of NiO NPs against SH-SY5Y was determined by MTT, LDH, caspase-9/3 activity, and expression of apoptotic Bax and Bcl-2 genes assays. DLS study showed that NiO solution had a good colloidal stability. Fluorescence study revealed that KSV values were 2.95 ±â€¯0.35 × 104, 3.31 ±â€¯0.59 × 104 and 3.92 ±â€¯0.65 × 104 at 298 K, 310 K and 315 K, respectively. Also, ∆G° (kJ/mol), ∆H° (kJ/mol) and T∆S° (kJ/mol) values were - 13.27 ±â€¯1.57, 1.98 ±â€¯0.14, 15.25 ±â€¯2.01, respectively at 298 K. Theoretical studies depicted that affinity of 5O3T segment toward NiO NP (30 Å) is higher than NiO NP (50 Å) and the proportion of Lys residues are higher in the docked pose of NiO NP (30 Å)/5O3T complex than NP (50 Å)/5O3T complex. Moreover, NiO NPs demonstrated a significant increase in the mortality of SH-SY5Y cells in an apoptotic manner. This study determined that NiO NPs may mediate the formation of electrostatic interactions with tau and induction of undesired harmful effects on neurons.


Assuntos
Apoptose/efeitos dos fármacos , Nanopartículas/química , Neurônios/metabolismo , Proteínas tau/metabolismo , Animais , Linhagem Celular , Neurônios/patologia , Níquel/química , Níquel/farmacologia , Ratos
18.
Int J Nanomedicine ; 14: 257-270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643405

RESUMO

Background: Recently, nanomaterials have moved into biological and medicinal implementations like cancer therapy. Therefore, before clinical trials, their binding to plasma proteins like human serum albumin (HSA) and their cytotoxic effects against normal and cancer cell lines should be addressed. Methods: Herein, the interaction of magnesium oxide nanoparticles (MgO NPs) with HSA was studied by means of fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and docking studies. Afterwards, the cytotoxic impacts of MgO NPs on human leukemia cell line (K562) and peripheral blood mononucleated cells (PBMCs) were evaluated by MTT and flow cytometry assays to quantify reactive oxygen species (ROS) generation and apoptosis. Results: It was demonstrated that MgO NPs spontaneously form a static complex with HSA molecules through hydrophobic interactions. Docking study based on the size of NPs demonstrated that different linkages can be established between MgO NPs and HSA. The CD investigation explored that MgO NPs did not alter the secondary structure of HSA. Cellular studies revealed that MgO NPs induced cytotoxicity against K562 cell lines, whereas no adverse effects were detected on PBMCs up to optimum applied concentration of MgO NPs. It was exhibited that ROS production mediated by IC50 concentrations of MgO NPs caused apoptosis-associated cell death. The pre-incubation of K562 with ROS scavenger (curcumin) inhibited the impact of MgO NPs -based apoptosis on cell fate, revealing the upstream effect of ROS in our system. Conclusion: In summary, MgO NPs may exhibit strong plasma distribution and mediate apoptosis by ROS induction in the cancer cell lines. These data demonstrate a safe aspect of MgO NPs on the proteins and normal cells and their application as a distinctive therapeutic approach in the cancer treatment.


Assuntos
Proliferação de Células/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Óxido de Magnésio/química , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Albumina Sérica Humana/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Simulação de Acoplamento Molecular , Conformação Proteica , Albumina Sérica Humana/química , Células Tumorais Cultivadas
19.
Int J Biol Macromol ; 124: 1312-1320, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30248427

RESUMO

The adverse effects of SiO2 NPs on the biological systems like nervous system have not been well explored. This study aimed to evaluate the toxicity of SiO2 NPs on the nervous system in vitro. Therefore, human tau protein and neuroblastoma cell line (SH-SY5Y) were used as targets. In this study we examined the side effects of SiO2 NPs on tau protein structure using several techniques including CD, ANS fluorescence, UV-vis (360 nm), Congo red absorbance, TEM, and molecular dynamic. Also, the cytotoxicity effects of SiO2 NPs against SH-SY5Y cell line were evaluated using MTT, ROS and apoptotic assays. Spectroscopic and molecular dynamic investigations indicated that natively unfolded structure of tau in the presence of SiO2 NPs experienced a partially folded and amorphous aggregated structure. Cellular assay demonstrated that SiO2 NPs exerted cytotoxic effect on SH-SY5Y cells through ROS accumulation and induction of apoptosis. Overall, these findings proved that SiO2 NPs could induce adverse effects on tau structure and SH-SY5Y cell integrity. Moreover, further studies are required to elucidate the molecular mechanism of SiO2 NPs-induced side effects in vivo.


Assuntos
Nanopartículas/química , Neurônios/efeitos dos fármacos , Espécies Reativas de Oxigênio/agonistas , Dióxido de Silício/farmacologia , Proteínas tau/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Simulação de Dinâmica Molecular , Neurônios/citologia , Estresse Oxidativo/efeitos dos fármacos , Conformação Proteica/efeitos dos fármacos , Dobramento de Proteína/efeitos dos fármacos , Dióxido de Silício/química , Proteínas tau/química , Proteínas tau/metabolismo
20.
Int J Biol Macromol ; 125: 674-682, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30468808

RESUMO

Manganese oxide nanoparticles (Mn2O3 NPs) have been widely used in the medical and biological applications. However, few studies have been undertaken to investigate the cytotoxicity of Mn2O3 NPs against nervous system. Herein, we studied the toxicity of Mn2O3 NPs against tau protein and neuroblastoma cells (SH-SY5Y) in vitro. Circular dichroism (CD) spectroscopy, fluorescence spectroscopy, molecular docking, and molecular dynamic studies were used to explore the conformational changes of protein. The cell-based experiments, such as viability, activation of caspases-3/9, apoptosis, and gene (Bax and Bcl-2) expression assays were performed in vitro. Spectroscopic methods and molecular dynamic studies revealed that Mn2O3 NPs can fold the structure of tau toward a more packed structure. The Mn2O3 NPs also decreased the cell viability in a dose-dependent manner. Indeed, caspase-3 and caspase-9 activation, Bax/Bcl-2 ratio elevation and apoptosis induction were observed after exposure of SH-SY5Y to Mn2O3 NPs. In conclusion, tau folding and cytotoxicity against SH-SY5Y cells may be involved in adverse effects induced by Mn2O3 NPs.


Assuntos
Compostos de Manganês/efeitos adversos , Nanopartículas Metálicas/efeitos adversos , Neuroblastoma/metabolismo , Óxidos/efeitos adversos , Dobramento de Proteína/efeitos dos fármacos , Proteínas tau/metabolismo , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular/métodos , Humanos , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
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