Human tau fibrillization and neurotoxicity in the presence of magnesium oxide nanoparticle fabricated through laser ablation method.

In this study, the acceleratory effect of magnesium oxide nanoparticles (MgO NPs) on the amyloid fibrillization of human tau protein, a major protein involved in the onset of Alzheimer's disease (AD) was investigated. The MgO NPs were fabricated through laser ablation synthesis in solution (LASiS), well-characterized, and explored further for tau aggregation and relevant neurotoxicity by different assays. The results showed that the MgO NPs have a size of around 30 nm, a hydrodynamic radius of 57.09 nm, and a zeta potential of -18.06 mV. The data from ThT and ANS fluorescence-based assays along with circular dichroism (CD) spectroscopy clearly indicated that MgO NPs could significantly promote tau fibrillization, concentration-dependently. Considering the acceleratory effect of MgO NPs against tau fibrillization, cellular assays including cell viability, reactive oxygen species (ROS), and caspase-3 assays indicated that the neurotoxicity of tau amyloid fibrils formed with MgO NPs was higher than that of tau samples aged alone against N2a neuron-like cells. Therefore, it was concluded that the interaction of MgO NPs with tau can lead to acceleration of tau aggregation and underlying neurotoxicity. This study, then can provide useful information about the direct effect of MgO NPs against memory proteins and subsequent adverse effects.

A review of the berberine natural polysaccharide nanostructures as potential anticancer and antibacterial agents.

Despite the promising medicinal properties, berberine (BBR), due to its relatively poor solubility in plasma, low bio-stability and limited bioavailability is not used broadly in clinical stages. Due to these drawbacks, drug delivery systems (DDSs) based on nanoscale natural polysaccharides, are applied to address these concerns. Natural polymers are biodegradable, non-immunogenic, biocompatible, and non-toxic agents that are capable of trapping large amounts of hydrophobic compounds in relatively small volumes. The use of nanoscale natural polysaccharide improves the stability and pharmacokinetics of the small molecules and, consequently, increases the therapeutic effects and reduces the side effects of the small molecules. Therefore, this paper presents an overview of the different methods used for increasing the BBR solubility and bioavailability. Afterwards, the pharmacodynamic and pharmacokinetic of BBR nanostructures were discussed followed by the introduction of natural polysaccharides of plant (cyclodextrines, glucomannan), the shells of crustaceans (chitosan), and the cell wall of brown marine algae (alginate)-based origins used to improve the dissolution rate of poorly soluble BBR and their anticancer and antibacterial properties. Finally, the anticancer and antibacterial mechanisms of free BBR and BBR nanostructures were surveyed. In conclusion, this review may pave the way for providing some useful data in the development of BBR-based platforms for clinical applications.

Diagnostic and drug release systems based on microneedle arrays in breast cancer therapy.

Microneedle arrays have recently received much attention as cancer detection and treatment platforms, because invasive injections and detection of the biopsy are not needed, and drug metabolism by the liver, as well as adverse effects of systemic drug administration, are diminished. Microneedles have been used for diagnosis, vaccination, and in targeted drug delivery of breast cancer. In this review, we summarize the recent progress in diagnosis and targeted drug delivery for breast cancer treatment, using microneedle arrays to deliver active molecules through the skin. The results not only suggest that health and well-being of patients are improved, but also that microneedle arrays can deliver anticancer compounds in a relatively noninvasive manner, based on body weight, breast tumor size, and circulation time of the drug. Moreover, microneedles could allow simultaneous loading of multiple drugs and enable controlled release, thus effectively optimizing or preventing drug-drug interactions. This review is designed to encourage the use of microneedles for diagnosis and treatment of breast cancer, by describing general properties of microneedles, materials used for construction, mechanism of action, and principal benefits. Ongoing challenges and future perspectives for the application of microneedle array systems in breast cancer detection and treatment are highlighted.

Magnetic nanocatalysts as multifunctional platforms in cancer therapy through the synthesis of anticancer drugs and facilitated Fenton reaction.

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions. Aim of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed.Key Scientific Concepts of Review:This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.

A review on the interaction of nucleoside analogues with SARS-CoV-2 RNA dependent RNA polymerase.

The outbreaks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in 2019, have highlighted the concerns about the lack of potential vaccines or antivirals approved for inhibition of CoVs infection. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA). However, ExoN proofreading activity of CoVs leads to their protection from several NAs. Therefore, potential platforms based on the development of efficient NAs with broad-spectrum efficacy against human CoVs should be explored. This study was then aimed to present an overview on the development of NAs-based drug repurposing for targeting SARS-CoV-2 RdRp by computational analysis. Afterwards, the clinical development of some NAs including Favipiravir, Sofosbuvir, Ribavirin, Tenofovir, and Remdesivir as potential inhibitors of RdRp, were surveyed. Overall, exploring broad-spectrum NAs as promising inhibitors of RdRp may provide useful information about the identification of potential antiviral repurposed drugs against SARS-CoV-2.

Characteristics, dynamics and mechanisms of actions of some major stress-induced biomacromolecules; addressing Artemia as an excellent biological model.

Stress tolerance is one of the most prominent and interesting topics in biology since many macro- and micro-adaptations have evolved in resistant organisms that are worth studying. When it comes to confronting various environmental stressors, the extremophile Artemia is unrivaled in the animal kingdom. In the present review, the evolved molecular and cellular basis of stress tolerance in resistant biological systems are described, focusing on Artemia cyst as an excellent biological model. The main purpose of the review is to discuss how the structure and physicochemical characteristics of protective factors such as late embryogenesis abundant proteins (LEAPs), small heat shock proteins (sHSPs) and trehalose are related to their functions and by which mechanisms, they exert their functions. In addition, some metabolic depressors in Artemia encysted embryos are also mentioned, indirectly playing important roles in stress tolerance. Importantly, a great deal of attention is given to the LEAPs, exhibiting distinctive folding behaviors and mechanisms of actions. For instance, molecular shield function, chaperone-like activity, moonlighting property, sponging and snorkeling capabilities of the LEAPs are delineated here. Moreover, the molecular interplay between some of these factors is mentioned, leading to their synergistic effects. Interestingly, Artemia life cycle adapts to environmental conditions. Diapause is the defense mode of this life cycle, safeguarding Artemia encysted embryos against various environmental stressors. Communicated by Ramaswamy H. Sarma.

Hydrothermal method-based synthesized tin oxide nanoparticles: Albumin binding and antiproliferative activity against K562 cells.

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.

Development of point-of-care nanobiosensors for breast cancers diagnosis.

Nanobiosensors have played a key role as portable devices in the rapid breast cancer diagnosis and in clinical medicine like point-of-care devices. However, understanding biomarkers and nanomaterials is crucial for improving the performance of nanobiosensors for all stages of different diseases or treatment. Therefore, this study not only investigates the effect of biomarkers and nanomaterials such as metallic, carbon structures and quantum dot on the accuracy of nanobiosensors for early detection of breast cancer, but also exhibits how they are used in vivo and in vitro and their application in point-of-care devices for personalized cancer diagnosis. Afterwards, application of fluidics and microchips as point-of-care nanobiosensors in the early detection of biomarkers associated with breast cancer diagnosis was discussed. Furthermore, the integration of nanobiosensors in nanomotors platforms for the treatment of breast cancer was overviewed. Finally, the ongoing challenges and future trends on the detection limit of nanobiosensors, their application in point-of-care clinical diagnostics and the approaches implemented for their improvements by highlighting the successful reports on the revolution of personalized diagnostics were surveyed.

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

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.

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

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.

Plasmonic gold nanoparticles: Optical manipulation, imaging, drug delivery and therapy.

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.

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

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.

Amorphous aggregation of tau in the presence of titanium dioxide nanoparticles: biophysical, computational, and cellular studies.

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.

A health concern regarding the protein corona, aggregation and disaggregation.

Nanoparticle (NP)-protein complexes exhibit the "correct identity" of NP in biological media. Therefore, protein-NP interactions should be closely explored to understand and modulate the nature of NPs in medical implementations. This review focuses mainly on the physicochemical parameters such as dimension, surface chemistry, morphology of NPs, and influence of pH on the formation of protein corona and conformational changes of adsorbed proteins by different kinds of techniques. Also, the impact of protein corona on the colloidal stability of NPs is discussed. Uncontrolled protein attachment on NPs may bring unwanted impacts such as protein denaturation and aggregation. In contrast, controlled protein adsorption by optimal concentration, size, pH, and surface modification of NPs may result in potential implementation of NPs as therapeutic agents especially for disaggregation of amyloid fibrils. Also, the effect of NPs-protein corona on reducing the cytotoxicity and clinical implications such as drug delivery, cancer therapy, imaging and diagnosis will be discussed. Validated correlative physicochemical parameters for NP-protein corona formation frequently derived from protein corona fingerprints of NPs which are more valid than the parameters obtained only on the base of NP features. This review may provide useful information regarding the potency as well as the adverse effects of NPs to predict their behavior in vivo.

Albumin binding, anticancer and antibacterial properties of synthesized zero valent iron nanoparticles.

BACKGROUND: Nanoparticles (NPs) have been emerging as potential players in modern medicine with clinical applications ranging from therapeutic purposes to antimicrobial agents. However, before applications in medical agents, some in vitro studies should be done to explore their biological responses. AIM: In this study, protein binding, anticancer and antibacterial activates of zero valent iron (ZVFe) were explored. MATERIALS AND METHODS: ZVFe nanoparticles were synthesized and fully characterized by X-ray diffraction, field-emission scanning electron microscope, and dynamic light scattering analyses. Afterward, the interaction of ZVFe NPs with human serum albumin (HSA) was examined using a range of techniques including intrinsic fluorescence, circular dichroism, and UV-visible spectroscopic methods. Molecular docking study was run to determine the kind of interaction between ZVFe NPs and HSA. The anticancer influence of ZVFe NPs on SH-SY5Y was examined by MTT and flow cytometry analysis, whereas human white blood cells were used as the control cell. Also, the antibacterial effect of ZVFe NPs was examined on Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), and Staphylococcus aureus (ATCC 25923). RESULTS: X-ray diffraction, transmission electron microscope, and dynamic light scattering analyses verified the synthesis of ZVFe NPs in a nanosized diameter. Fluorescence spectroscopy analysis showed that ZVFe NPs spontaneously formed a complex with HSA through hydrogen bonds and van der Waals interactions. Also, circular dichroism spectroscopy study revealed that ZVFe NPs did not change the secondary structure of HSA. Moreover, UV-visible data presented that melting temperature (Tm) of HSA in the absence and presence of ZVFe NPs was almost identical. Molecular dynamic study also showed that ZVFe NP came into contact with polar residues on the surface of HSA molecule. Cellular assays showed that ZVFe NPs can induce cell mortality in a dose-dependent manner against SH-SY5Y cells, whereas these NPs did not trigger significant cell mortality against normal white bloods in the concentration range studied (1-100 µg/mL). Antibacterial assays showed a noteworthy inhibition on both bacterial strains. CONCLUSION: In conclusion, it was revealed that ZVFe NPs did not induce a substantial influence on the structure of protein and cytotoxicity against normal cell, whereas they derived significant anticancer and antibacterial effects.

Albumin binding and anticancer effect of magnesium oxide nanoparticles.

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.

The effects of nickel oxide nanoparticles on tau protein and neuron-like cells: Biothermodynamics and molecular studies.

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.

Cancer diagnosis using nanomaterials based electrochemical nanobiosensors.

Cancer is one of the most important causes of mortality in the world, which can be severely reduced by early detection to avoid future problems in the field of economics and mental health. Hence, electrochemical nanobiosensors as portable devices for rapid detection of  cancer biomarkers, have found an important place in clinical medicine for diagnosis, managements or cancer screening. Although, these biosensors have been receiving attention in the recent years, their principles are unchanged. By progress in nanotechnology, a great potential has been giving to nanobiosensors. Applications of a wide variety of nanomaterials in developing electrochemical biosensors, led to the production of potential nanobiosensors. Due to the high electrical conductivity, and increased surface area relative to the volume along with more repeatability, the application of NPs in electrochemical biosensors has been developed. Therefore, in this review, we discussed the impact of nanomaterials on the accuracy of biosensors in early cancer detection such as lung, prostate, breast, and other cancers. However, the modification of electrode performance by nanomaterials is relatively complicated, which causes limitation for some nanomaterials to be used inbiosensor applications. Indeed, the construction of electrodes based on nanomaterial requires a simple, reliable and inexpensive route to increase the sensitivity and reproducibility. Thus, the aim of this study can be defined as determining the detection limit of electrochemical nanobiosensors as well as introducing the challenges of fabricating and designing electrochemical nanobiosensors based on nanomaterials and their evaluations in the future medical setting.

Biophysical, bioinformatical, cellular, and molecular investigations on the effects of graphene oxide nanosheets on the hemoglobin structure and lymphocyte cell cytotoxicity.

BACKGROUND: Implementations of nanoparticles have been receiving great interest in medicine and technology due to their unique characteristics. However, their toxic impacts on the biological system are not well explored. AIM: This study aims to investigate the influence of fabricated nano graphene oxide (NGO) sheets on the secondary and quaternary structural alterations of human hemoglobin (Hb) and cytotoxicity against lymphocyte cells. MATERIALS AND METHODS: Different spectroscopic methods, such as extrinsic and synchronous fluorescence spectroscopy and far circular dichroism (CD) spectroscopy, molecular docking investigation, cellular assays (trypan blue exclusion, cellular uptake, ROS, cell cycle, and apoptosis), and molecular assay (fold changes in anti/proapoptotic genes [B-cell lymphoma-2 {BCL2}/BAX] expression levels) were used in this study. RESULTS: Transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and zeta potential investigations revealed the nano-sized nature of NGOs with good colloidal stability. Extrinsic fluorescence spectroscopy by using 8-anilinonaphthalene-1 -sulfonic acid and synchronous fluorescence spectroscopy showed that NGOs can unfold the quaternary structure of Hb in the vicinity of Tyr residues. The CD investigation demonstrated that the α-helicity of Hb experienced substantial alteration upon interaction with increasing concentrations of NGOs. The molecular docking study showed that NGOs interacted with polar residues of Hb. Cellular and molecular assays revealed that NGOs lead to ROS formation, cell cycle arrest, and apoptosis through the BAX and BCL2 pathway. CONCLUSION: These data reveal that NGOs can induce some protein structural changes and stimulate cytotoxicity against normal cell targets. Therefore, their applications in healthy systems should be limited.

Heme degradation and iron release of hemoglobin and oxidative stress of lymphocyte cells in the presence of silica nanoparticles.

Silica nanoparticles (SiO2 NPs) have been widely used in the medical and food sciences. However, their toxic effects against bio-macromolecules and cells are not well understood. The present study was aimed to investigate the adverse effects of fabricated SiO2 NPs on the human hemoglobin (Hb) by FTIR, CD, fluorescence, and UV-vis spectroscopic techniques. Moreover, the toxic effects of SiO2 NPs on the human lymphocyte cell was assessed by trypan blue, reactivate oxygen species (ROS), and apoptosis assays. It was shown that synthesized SiO2 NPs have an amorphous structure with dominant size of around 20-30 nm. FTIR results showed that SiO2 NPs bind to Hb and induce significant structural changes on the native structure of Hb. Near CD spectroscopy depicted that SiO2 NPs induced tertiary structural changes and heme displacement. Fluorescence spectroscopy demonstrated the production of heme degradation species in the Hb solution after interaction with SiO2 NPs. UV-vis spectroscopy experiment indicated the release of iron form Hb after interaction with SiO2 NPs in a concentration dependent manner. Live-dead staining, ROS detection and flow cytometry analysis revealed that human lymphocyte was sensitive towards the toxicity of SiO2 NPs in a ROS-mediated apoptosis mechanism. In conclusion, SiO2 NPs exhibited concentration-dependent toxicity.