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1.
Biointerphases ; 19(4)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39007691

ABSTRACT

Retinal degenerative diseases, which can lead to photoreceptor cell apoptosis, have now become the leading irreversible cause of blindness worldwide. In this study, we developed an organic photovoltaic biomaterial for artificial retinas, enabling neural cells to detect photoelectric stimulation. The biomaterial was prepared using a conjugated polymer donor, PCE-10, and a non-fullerene receptor, Y6, both known for their strong near-infrared light absorption capabilities. Additionally, a fullerene receptor, PC61BM, was incorporated, which possesses the ability to absorb reactive oxygen species. We conducted a comprehensive investigation into the microstructure, photovoltaic properties, and photothermal effects of this three-component photovoltaic biomaterial. Furthermore, we employed Rat adrenal pheochromocytoma cells (PC-12) as a standard neural cell model to evaluate the in vitro photoelectric stimulation effect of this photovoltaic biomaterial. The results demonstrate that the photovoltaic biomaterial, enriched with fullerene derivatives, can induce intracellular calcium influx in PC-12 cells under 630 nm (red light) and 780 nm (near-infrared) laser irradiation. Moreover, there were lower levels of oxidative stress and higher levels of mitochondrial activity compared to the non-PC61BM group. This photovoltaic biomaterial proves to be an ideal substrate for near-infrared photoelectrical stimulation of neural cells and holds promise for restoring visual function in patients with photoreceptor apoptosis.


Subject(s)
Biocompatible Materials , Fullerenes , Infrared Rays , Animals , Fullerenes/chemistry , Fullerenes/pharmacology , Rats , Biocompatible Materials/chemistry , PC12 Cells , Neurons/drug effects , Neurons/radiation effects , Calcium/metabolism , Calcium/chemistry
2.
Molecules ; 29(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38998903

ABSTRACT

The liver is the main organ responsible for the metabolism of ethanol, which suffers significantly as a result of tissue damage due to oxidative stress. It is known that C60 fullerenes are able to efficiently capture and inactivate reactive oxygen species in in vivo and in vitro systems. Therefore, the purpose of this study is to determine whether water-soluble C60 fullerene reduces the level of pathological process development in the liver of rats induced by chronic alcohol intoxication for 3, 6, and 9 months, depending on the daily dose (oral administration; 0.5, 1, and 2 mg/kg) of C60 fullerene throughout the experiment. In this context, the morphology of the C60 fullerene nanoparticles in aqueous solution was studied using atomic force microscopy. Such biochemical parameters of experimental animal blood as ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase) and ALP (alkaline phosphatase) enzyme activities, CDT (carbohydrate-deficient transferrin) level, values of pro-antioxidant balance indicators (concentrations of H2O2 (hydrogen peroxide) and GSH (reduced glutathione), activities of CAT (catalase), SOD (superoxide dismutase) and GPx (selenium-dependent glutathione peroxidase)), and pathohistological and morphometric features of liver damage were analyzed. The most significant positive change in the studied biochemical parameters (up to 29 ± 2% relative to the control), as markers of liver damage, was recorded at the combined administration of alcohol (40% ethanol in drinking water) and water-soluble C60 fullerenes in the optimal dose of 1 mg/kg, which was confirmed by small histopathological changes in the liver of rats. The obtained results prove the prospective use of C60 fullerenes as powerful antioxidants for the mitigation of pathological conditions of the liver arising under prolonged alcohol intoxication.


Subject(s)
Fullerenes , Liver , Oxidative Stress , Animals , Fullerenes/pharmacology , Rats , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Oxidative Stress/drug effects , Antioxidants/pharmacology , Alcoholic Intoxication/drug therapy , Alcoholic Intoxication/metabolism , Rats, Wistar , Nanoparticles/chemistry , Ethanol/toxicity
3.
Int J Nanomedicine ; 19: 6035-6055, 2024.
Article in English | MEDLINE | ID: mdl-38911505

ABSTRACT

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments. Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining. Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment. Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment.


Subject(s)
Autism Spectrum Disorder , Cognitive Dysfunction , Disease Models, Animal , Doublecortin Protein , Fullerenes , Mice, Inbred C57BL , Animals , Mice , Fullerenes/pharmacology , Fullerenes/chemistry , Autism Spectrum Disorder/drug therapy , Cognitive Dysfunction/drug therapy , Male , Social Behavior , Behavior, Animal/drug effects , Hippocampus/drug effects , Vascular Endothelial Growth Factor A/genetics , Neuroprotective Agents/pharmacology , Neurogenesis/drug effects , Autistic Disorder/drug therapy
4.
Langmuir ; 40(27): 13844-13859, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38916256

ABSTRACT

Fullerene-based biosensors have received great attention due to their unique electronic properties that allow them to transduce electrical signals by accepting electrons from amino acids. Babies with MSUD (maple syrup urine disease) are unable to break down amino acids such as l-leucine, and excess levels of the l-leucine are harmful. Therefore, sensing of l-leucine is foremost required. We aim to investigate the interaction tendencies of size-variable fullerenes (CX; X = 24, 36, 50, and 70) toward l-leucine (LEU) using density functional theory (DFT-D3) and classical molecular dynamics (MD) simulation. The C24 fullerene shows the highest affinity of the LEU biomolecule in the gas phase. Smaller fullerenes (C24 and C36) show stronger interactions with leucine due to their higher curvature in water environments. Moreover, recovery times in the ranges of 1010 and 104 s make it a viable candidate for the isolation application of LEU from the biological system. Further, the interaction between LEU and fullerenes is in line with the natural bond order (NBO) analysis, Mulliken charge analysis, quantum theory atom in molecule (QTAIM) analysis, and reduced density gradient (RDG) analysis. At 310 K, employing the explicit water model in classical MD simulations, fullerenes C24 and C36 demonstrate notably elevated binding free energies (-24.946 kJ/mol) in relation to LEU, showcasing their potential as sensors for l-leucine. Here, we demonstrate that the smaller fullerene exhibits a higher potential for l-leucine sensors than the larger fullerene.


Subject(s)
Density Functional Theory , Fullerenes , Leucine , Molecular Dynamics Simulation , Fullerenes/chemistry , Leucine/chemistry , Particle Size
5.
Int J Pharm ; 660: 124313, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38857663

ABSTRACT

Nanomaterials have become increasingly important over time as research technology has enabled the progressively precise study of materials at the nanoscale. Developing an understanding of how nanomaterials are produced and tuned allows scientists to utilise their unique properties for a variety of applications, many of which are already incorporated into commercial products. Fullerenol nanoparticles C60(OH)n, 2 ≤ n ≤ 44 are fullerene derivatives and are produced synthetically. They have good biocompatibility, low toxicity and no immunological reactivity. In addition, their nanometre size, large surface area to volume ratio, ability to penetrate cell membranes, adaptable surface that can be easily modified with different functional groups, drug release, high physical stability in biological media, ability to remove free radicals, magnetic and optical properties make them desirable candidates for various applications. This review comprehensively summarises the various applications of fullerenol nanoparticles in different scientific fields such as nanobiomedicine, including antibacterial and antiviral agents, and provides an overview of their use in agriculture and biosensor technology. Recommendations are also made for future research that would further elucidate the mechanisms of fullerenols actions.


Subject(s)
Fullerenes , Nanoparticles , Fullerenes/chemistry , Nanoparticles/chemistry , Humans , Animals , Biosensing Techniques/methods , Nanomedicine/methods , Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology
6.
ACS Nano ; 18(24): 15416-15431, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38840269

ABSTRACT

The accumulation of amyloid-ß (Aß) peptides is a major hallmark of Alzheimer's disease (AD) and plays a crucial role in its pathogenesis. Particularly, the structured oligomeric species rich in ß-sheet formations were implicated in neuronal organelle damage. Addressing this formidable challenge requires identifying candidates capable of inhibiting peptide aggregation or disaggregating preformed oligomers for effective antiaggregation-based AD therapy. Here, we present a dual-functional nanoinhibitor meticulously designed to target the aggregation driving force and amyloid fibril spatial structure. Leveraging the exceptional structural stability and facile tailoring capability of endohedral metallofullerene Gd@C82, we introduce desired hydrogen-binding sites and charged groups, which are abundant on its surface for specific designs. Impressively, these designs endow the resultant functionalized-Gd@C82 nanoparticles (f-Gd@C82 NPs) with high capability of redirecting peptide self-assembly toward disordered, off-pathway species, obstructing the early growth of protofibrils, and disaggregating the preformed well-ordered protofibrils or even mature Aß fibrils. This results in considerable alleviation of Aß peptide-induced neuronal cytotoxicity, rescuing neuronal death and synaptic loss in primary neuron models. Notably, these modifications significantly improved the dispersibility of f-Gd@C82 NPs, thus substantially enhancing its bioavailability. Moreover, f-Gd@C82 NPs demonstrate excellent cytocompatibility with various cell lines and possess the ability to penetrate the blood-brain barrier in mice. Large-scale molecular dynamics simulations illuminate the inhibition and disaggregation mechanisms. Our design successfully overcomes the limitations of other nanocandidates, which often overly rely on hydrophobic interactions or photothermal conversion properties, and offers a viable direction for developing anti-AD agents through the inhibition and even reversal of Aß aggregation.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Neurons , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Animals , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Humans , Gadolinium/chemistry , Gadolinium/pharmacology , Nanoparticles/chemistry , Fullerenes/chemistry , Fullerenes/pharmacology , Protein Aggregates/drug effects , Mice , Drug Design , Cell Survival/drug effects , Rats
7.
Talanta ; 277: 126397, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38865956

ABSTRACT

Graphene-based nanomaterials have attracted significant attention for their potentials in biomedical and biotechnology applications in recent years, owing to the outstanding physical and chemical properties. However, the interaction mechanism and impact on biological activity of macro/micro biomolecules still require more concerns and further research in order to enhance their applicability in biosensors, etc. Herein, an integrated method has been developed to predict the protein bioactivity performance when interacting with nanomaterials for protein-based biosensor. Molecular dynamics simulation and molecular docking technique were consolidated to investigate several nanomaterials: C60 fullerene, single-walled carbon nanotube, pristine graphene and graphene oxide, and their effect when interacting with protein. The adsorption behavior, secondary structure changes and protein bioactivity changes were simulated, and the results of protein activity simulation were verified in combination with atomic force spectrum, circular dichroism spectrum fluorescence and electrochemical experiments. The best quantification alignment between bioactivity obtained by simulation and experiment measurements was further explored. The two proteins, RNase A and Exonuclease III, were regarded as analysis model for the proof of concept, and the prediction accuracy of protein bioactivity could reach up to 0.98. The study shows an easy-to-operate and systematic approach to predict the effects of graphene-based nanomaterials on protein bioactivity, which holds guiding significance for the design of protein-related biosensors. In addition, the proposed prediction model is not limited to carbon-based nanomaterials and can be extended to other types of nanomaterials. This facilitates the rapid, simple, and low-cost selection of efficient and biosafe nanomaterials candidates for protein-related applications in biosensing and biomedical systems.


Subject(s)
Biosensing Techniques , Fullerenes , Graphite , Molecular Docking Simulation , Molecular Dynamics Simulation , Nanostructures , Nanotubes, Carbon , Graphite/chemistry , Biosensing Techniques/methods , Nanotubes, Carbon/chemistry , Fullerenes/chemistry , Nanostructures/chemistry , Proteins/chemistry , Proteins/analysis , Proteins/metabolism , Adsorption , Computer Simulation
8.
Plant Physiol Biochem ; 212: 108753, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38781637

ABSTRACT

Biocompounds are metabolites synthesized by plants, with clinically proven capacity in preventing and treating degenerative diseases in humans. Carbon-based nanomaterials (CNMs) are atomic structures that assume different hybridization and shape. Due to the reactive property, CNMs can induce the synthesis of metabolites, such as biocompounds in cells and various plant species, by generating reactive oxygen species (ROS). In response, plants positively or negatively regulate the expression of various families of genes and enzymes involved in physiological and metabolomic pathways of plants, such as carbon and nitrogen metabolism, which are directly involved in plant development and growth. Likewise, ROS can modulate the expression of enzymes and genes related to the adaptation of plants to stress, such as the glutathione ascorbate cycle, the shikimic acid, and phenylpropanoid pathways, from which the largest amount of biocompounds in plants are derived. This document exposes the ability of three CNMs (fullerene, graphene, and carbon nanotubes) to positively or negatively regulate the activity of enzymes and genes involved in various plant species' primary and secondary metabolism. The mechanism of action of CNMs on the production of biocompounds and the effect of the translocation of CNMs on the growth and content of primary metabolites in plants are described. Adverse effects of CNMs on plants, prospects, and possible risks involved are also discussed. The use of CNMs as inducers of biocompounds in plants could have implications and relevance for human health, crop quality, and plant adaptation and resistance to biotic and abiotic stress.


Subject(s)
Nanostructures , Plants , Nanostructures/chemistry , Plants/metabolism , Plants/drug effects , Reactive Oxygen Species/metabolism , Carbon/metabolism , Nanotubes, Carbon , Fullerenes/pharmacology , Fullerenes/metabolism , Graphite
9.
J Mol Graph Model ; 131: 108792, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38797085

ABSTRACT

In the current quantum chemical study, indacenodithiophene donor core-based the end-capped alterations of the reference chromophore BTR drafted eight A2-A1-D-A1-A2 type small non-fullerene acceptors. All the computational simulations were executed under MPW1PW91/6-31G (d, p) level of DFT. The UV-Vis absorption, open circuit voltage, electron affinity, ionization potential, the density of states, reorganization energy, orbital analysis, and non-covalent interactions were studied and compared with BTR. Several molecules of our modeled series BT1-BT8 have shown distinctive features that are better than those of the BTR. The open circuit voltage (VOC) of BT5 has a favorable impact, allowing it to replace BTR in the field of organic solar cells. The charge carrier motilities for proposed molecules generated extraordinary findings when matched to the reference one (BTR). Further charge transmission was confirmed by creating the complex with a PM6 donor molecule. The remarkable dipole moment contributes to the formation of non-covalent bond interactions with chloroform, resulting in superior charge mobility. Based on these findings, it can be said that every tailored molecule has the potential to surpass chromophore molecule (BTR) in OSCs. So, all tailored molecules may enhance the efficiency of photovoltaic cells due to the involvement of potent terminal electron-capturing acceptor2 moieties. Considering these obtained results, these newly presented molecules can be regarded for developing efficient solar devices in the future.


Subject(s)
Electrons , Fullerenes , Solar Energy , Fullerenes/chemistry , Models, Molecular , Quantum Theory , Thiophenes/chemistry , Molecular Structure
10.
J Mol Model ; 30(6): 166, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744728

ABSTRACT

CONTEXT: Coronavirus (COVID-19) is a novel respiratory viral infection, causing a relatively large number of deaths especially in people who underly lung diseases such as chronic obstructive pulmonary and asthma, and humans are still suffering from the limited testing capacity. In this article, a solution is proposed for the detection of COVID-19 viral infections through the analysis of exhaled breath gasses, i.e., nitric oxide, a prominent biomarker released by respiratory epithelial, as a non-invasive and time-saving approach. Here, we designed a novel and low-cost N and P co-doped C60 fullerene-based breathalyzer for the detection of NO gas exhaled from the respiratory epithelial cells. This breathalyzer shows a quick response to the detection of NO gas by directly converting NO to NO2 without passing any energy barrier (0 kcal/mol activation energy). The recovery time of breathalyzer is very short (0.98 × 103 s), whereas it is highly selective for NO sensing in the mixture of CO2 and H2O gasses. The study provides an idea for the synthesis of low-cost (compared to previously reported Au atom decorated nanostructure and metal-based breathalyzer), efficient, and highly selective N and P co-doped C60 fullerene-based breathalyzer for COVID-19 detection. METHODS: The geometries of N and P-doped systems and gas molecules are simulated using spin-polarized density functional theory calculations.


Subject(s)
Biomarkers , COVID-19 , Fullerenes , Nitric Oxide , Fullerenes/chemistry , Humans , Nitric Oxide/analysis , Nitric Oxide/chemistry , COVID-19/virology , COVID-19/diagnosis , Breath Tests/methods , SARS-CoV-2
11.
Sci Rep ; 14(1): 11988, 2024 05 25.
Article in English | MEDLINE | ID: mdl-38796555

ABSTRACT

This study employs a combination of mathematical derivation and optimization technique to investigate the adsorption of drug molecules on nanocarriers. Specifically, the chemotherapy drugs, fluorouracil, proflavine, and methylene blue, are non-covalently bonded with either a flat graphene sheet or a spherical C 60 fullerene. Mathematical expressions for the interaction energy between an atom and graphene, as well as between an atom and C 60 fullerene, are derived. Subsequently, a discrete summation is evaluated for all atoms on the drug molecule utilizing the U-NSGA-III algorithm. The stable configurations' three-dimensional architectures are presented, accompanied by numerical values for crucial parameters. The results indicate that the nanocarrier's structure effectively accommodates the atoms on the drug's carbon planes. The three drug types' molecules disperse across the graphene surface, whereas only fluorouracil spreads on the C 60 surface; proflavine and methylene blue stack vertically to form a layer. Furthermore, all atomic positions of equilibrium configurations for all systems are obtained. This hybrid method, integrating analytical expressions and an optimization process, significantly reduces computational time, representing an initial step in studying the binding of drug molecules on nanocarriers.


Subject(s)
Drug Carriers , Fluorouracil , Graphite , Methylene Blue , Adsorption , Graphite/chemistry , Methylene Blue/chemistry , Fluorouracil/chemistry , Drug Carriers/chemistry , Models, Theoretical , Algorithms , Fullerenes/chemistry , Carbon/chemistry , Proflavine/chemistry , Nanoparticles/chemistry , Antibiotics, Antineoplastic/chemistry , Antineoplastic Agents/chemistry
12.
Int J Biol Macromol ; 271(Pt 2): 132399, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38754684

ABSTRACT

The neutrophil-derived peptide, indolicidin, and the sphere-shaped carbon nanoparticle, C60, are contemporary components capable of acting as bactericides and virucides, among others. Herein, the coarse-grained molecular dynamics simulation method was used to simulate the interactions of gram-negative bacteria, eukaryotes, human immunodeficiency virus (HIV), and SARS-COV-2 membrane models with indolicidin, C60s, and C60-indolicidin hybrids. Our results demonstrated that the carbon nanoparticle penetrated all membrane models, except the bacterial membrane, which remained impenetrable to both the peptide and C60. Additionally, the membrane thickness did not change significantly. The peptide floated above the membranes, with only the side chains of the tryptophan (Trp)-rich site slightly permeating the membranes. After achieving stable contact between the membrane models and nanoparticles, the infiltrated C60s interacted with the unsaturated tail of phospholipids. The density results showed that C60s stayed close to indolicidin and continued to interact with it even after penetration. Indolicidin, especially its Trp-rich site, exhibited more contact with the head and tail of neutral phospholipids compared to other phospholipids. Moreover, both particles interacted with different kinds of glycosphingolipids located in the eukaryote membrane. This investigation has the potential to advance our knowledge of novel approaches to combat antimicrobial resistance.


Subject(s)
COVID-19 , Fullerenes , Molecular Dynamics Simulation , SARS-CoV-2 , Fullerenes/chemistry , Fullerenes/pharmacology , SARS-CoV-2/drug effects , Humans , COVID-19/virology , Cell Membrane/chemistry , Cell Membrane/metabolism , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , HIV/drug effects , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology
13.
Biomed Pharmacother ; 176: 116828, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38810406

ABSTRACT

BACKGROUND: Fullerenes C60 shows great potential for drug transport. C60 generates large amounts of singlet oxygen upon photoexcitation, which has a significant inhibitory effect on tumor cells, so the photosensitive properties of C60 were exploited for photodynamic therapy of tumors by laser irradiation. METHODS: In this study, C60-NH2 was functionalized by introducing amino acids on the surface of C60, coupled with 5-FU to obtain C60 amino acid-derived drugs (C60AF, C60GF, C60LF), and activated photosensitive drugs (C60AFL, C60GFL, C60LFL) were obtained by laser irradiation. The C60 nano-photosensitive drugs were characterized in various ways, and the efficacy and safety of C60 nano-photosensitive drugs were verified by cellular experiments and animal experiments. Bioinformatics methods and cellular experiments were used to confirm the photosensitive drug targets and verify the therapeutic targets with C60AF. RESULTS: Photosensitised tumor-targeted drug delivery effectively crosses cell membranes, leads to more apoptotic cell death, and provides higher anti-tumor efficacy and safety in vitro and in vivo colorectal cancer pharmacodynamic assays compared to free 5-FU.C60 photosensitized drug promotes tumor killing by inhibiting the colorectal cancer FLOR1 tumor protein target, with no significant toxic effects on normal organs. CONCLUSION: C60 photosensitized drug delivery systems are expected to improve efficacy and reduce side effects in the future treatment of colorectal cancer. Further and better development and design of drugs and vectors for colorectal cancer therapy.


Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Fullerenes , Nanoparticle Drug Delivery System , Photosensitizing Agents , Fullerenes/chemistry , Nanoparticle Drug Delivery System/chemical synthesis , Nanoparticle Drug Delivery System/standards , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemistry , Colorectal Neoplasms/drug therapy , Amino Acids/chemistry , Fluorouracil/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , HT29 Cells , Apoptosis/drug effects , Cell Movement/drug effects , Reactive Oxygen Species/metabolism , Humans , Animals , Mice , Light
14.
Molecules ; 29(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731411

ABSTRACT

Fullerenes, particularly C60, exhibit unique properties that make them promising candidates for various applications, including drug delivery and nanomedicine. However, their interactions with biomolecules, especially proteins, remain not fully understood. This study implements both explicit and implicit C60 models into the UNRES coarse-grained force field, enabling the investigation of fullerene-protein interactions without the need for restraints to stabilize protein structures. The UNRES force field offers computational efficiency, allowing for longer timescale simulations while maintaining accuracy. Five model proteins were studied: FK506 binding protein, HIV-1 protease, intestinal fatty acid binding protein, PCB-binding protein, and hen egg-white lysozyme. Molecular dynamics simulations were performed with and without C60 to assess protein stability and investigate the impact of fullerene interactions. Analysis of contact probabilities reveals distinct interaction patterns for each protein. FK506 binding protein (1FKF) shows specific binding sites, while intestinal fatty acid binding protein (1ICN) and uteroglobin (1UTR) exhibit more generalized interactions. The explicit C60 model shows good agreement with all-atom simulations in predicting protein flexibility, the position of C60 in the binding pocket, and the estimation of effective binding energies. The integration of explicit and implicit C60 models into the UNRES force field, coupled with recent advances in coarse-grained modeling and multiscale approaches, provides a powerful framework for investigating protein-nanoparticle interactions at biologically relevant scales without the need to use restraints stabilizing the protein, thus allowing for large conformational changes to occur. These computational tools, in synergy with experimental techniques, can aid in understanding the mechanisms and consequences of nanoparticle-biomolecule interactions, guiding the design of nanomaterials for biomedical applications.


Subject(s)
Fullerenes , Molecular Dynamics Simulation , Muramidase , Protein Binding , Fullerenes/chemistry , Muramidase/chemistry , Muramidase/metabolism , Binding Sites , Tacrolimus Binding Proteins/chemistry , Tacrolimus Binding Proteins/metabolism , Fatty Acid-Binding Proteins/chemistry , Fatty Acid-Binding Proteins/metabolism , Proteins/chemistry , Proteins/metabolism , HIV Protease
15.
Int J Mol Sci ; 25(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38791388

ABSTRACT

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C60 conjugate (FA-PVP-C60) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using 13C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C60 showed antiradical activity against •DPPH, •OH and O2•-, but at the same time, it was shown to generate 1O2. It was found that the conjugate in the studied concentration range (up to 200 µg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor.


Subject(s)
Drug Delivery Systems , Folic Acid , Fullerenes , Povidone , Folic Acid/chemistry , Folic Acid/pharmacology , Humans , Povidone/chemistry , Fullerenes/chemistry , Fullerenes/pharmacology , Drug Delivery Systems/methods , Cell Line, Tumor , A549 Cells , HeLa Cells , Particle Size
16.
Free Radic Biol Med ; 220: 236-248, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38704052

ABSTRACT

Alcoholic liver disease (ALD) is a common chronic redox disease caused by increased alcohol consumption. Abstinence is a major challenge for people with alcohol dependence, and approved drugs have limited efficacy. Therefore, this study aimed to explore a new treatment strategy for ALD using ferroferric oxide endohedral fullerenol (Fe3O4@C60(OH)n) in combination with static magnetic and electric fields (sBE). The primary hepatocytes of 8-9-week-old female BALB/c mice were used to evaluate the efficacy of the proposed combination treatment. A mouse chronic binge ethanol feeding model was established to determine the alleviatory effect of Fe3O4@C60(OH)n on liver injury under sBE exposure. Furthermore, the ability of Fe3O4@C60(OH)n to eliminate •OH was evaluated. Alcohol-induced hepatocyte and mitochondrial damage were reversed in vitro. Additionally, the combination therapy reduced liver damage, alleviated oxidative stress by improving antioxidant levels, and effectively inhibited liver lipid accumulation in animal experiments. Here, we used a combination of magnetic derivatives of fullerenol and sBE to further improve the ROS clearance rate, thereby alleviating ALD. The developed combination treatment may effectively improve alcohol-induced liver damage and maintain redox balance without apparent toxicity, thereby enhancing therapy aimed at ALD and other redox diseases.


Subject(s)
Fullerenes , Hepatocytes , Liver Diseases, Alcoholic , Mice, Inbred BALB C , Oxidative Stress , Reactive Oxygen Species , Animals , Fullerenes/pharmacology , Fullerenes/chemistry , Fullerenes/therapeutic use , Mice , Reactive Oxygen Species/metabolism , Female , Hepatocytes/metabolism , Hepatocytes/drug effects , Hepatocytes/pathology , Oxidative Stress/drug effects , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/pathology , Liver Diseases, Alcoholic/drug therapy , Liver/metabolism , Liver/pathology , Liver/drug effects , Antioxidants/pharmacology , Disease Models, Animal , Humans , Oxidation-Reduction/drug effects , Ethanol/toxicity
17.
Adv Sci (Weinh) ; 11(23): e2310245, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38647389

ABSTRACT

Natural photosynthesis holds great potential to generate clean electricity from solar energy. In order to utilize this process for power generation, it is necessary to rewire photosynthetic electron transport chains (PETCs) of living photosynthetic organisms to redirect more electron flux toward an extracellular electrode. In this study, a semi-artificial rewiring strategy, which use a water-soluble fullerene derivative to capture electrons from PETCs and donate them for electrical current generation, is proposed. A positively charged fullerene derivative, functionalized with N,N-dimethyl pyrrolidinium iodide, is found to be efficiently taken up by the cyanobacterium Synechocystis sp. PCC 6803. The distribution of this fullerene derivative near the thylakoid membrane, as well as site-specific inhibitor assays and transient absorption spectroscopy, suggest that it can directly interact with the redox centers in the PETCs, particularly the acceptor side of photosystem I (PSI). The internalized fullerene derivatives facilitate the extraction of photosynthetic electrons and significantly enhance the photocurrent density of Synechocystis by approximately tenfold. This work opens up new possibility for the application of fullerenes as an excellent 3D electron carrier in living biophotovoltaics.


Subject(s)
Fullerenes , Photosynthesis , Solar Energy , Synechocystis , Fullerenes/chemistry , Synechocystis/metabolism , Water/metabolism , Water/chemistry , Electron Transport , Electricity
18.
Sci Prog ; 107(2): 368504241239444, 2024.
Article in English | MEDLINE | ID: mdl-38614462

ABSTRACT

BACKGROUND: Ischemia-reperfusion injury (IRI) poses a significant challenge for physicians, necessitating the management of cell damage and the preservation of organ functions. Various surgical procedures, such as vascular surgery on extremities, temporary cross-clamping of the abdominal aorta in aortic surgery, and the use of a tourniquet in extremity surgeries, may induce lower limb IRI. The susceptibility to IRI is heightened in individuals with diabetes. This study aimed to investigate the effects of fullerenol C60 and sevoflurane on mouse muscle tissue in a lower limb IRI model and to assess their potential in preventing complications arising from ischemia-reperfusion in mice with streptozocin-induced diabetes. METHODS: A total of 36 adult Swiss albino mice were randomly divided into six groups, each consisting of six mice: control group (group C), diabetes group (group D), diabetes-ischemia/reperfusion group (group DIR), diabetes-ischemia/reperfusion-fullerenol C60 group (group DIR-FC60), diabetes-ischemia/reperfusion-sevoflurane group (group DIR-S), and diabetes-ischemia/reperfusion-sevoflurane-fullerenol C60 group (DIR-S-FC60). Streptozocin (55 mg/kg) was intraperitoneally administered to induce diabetes in the relevant groups, with mice displaying blood glucose levels of 250 mg/dL or higher at 72 h were considered diabetic. After 4 weeks, all groups underwent laparotomy under anesthesia. In DIR-FC60 and DIR-S-FC60 groups, fullerenol C60 (100 mg/kg) was intraperitoneally administrated 30 min before the ischemia period. Sevoflurane, delivered in 100% oxygen at a rate of 2.3% and 4 L/min, was administered during the ischemia period in DIR-S and DIR-S-FC60 groups. In the IR groups, a microvascular clamp was placed on the infrarenal abdominal aorta for 120 min during the ischemia period, followed by the removal of the clamp and a 120-min reperfusion period. At the end of the reperfusion, gastrocnemius muscle tissues were removed for histopathological and biochemical parameter examinations. RESULTS: Histopathological examination revealed a significant reduction in the disorganization and degeneration of muscle cells in the DIR-S-FC60 group compared to the DIR group (p = 0.041). Inflammatory cell infiltration was notably lower in the DIR-S, DIR-FC60, and DIR-S-FC60 groups than in the DIR group (p = 0.031, p = 0.011, and p = 0.013, respectively). The total damage scores in the DIR-FC60 and DIR-S-FC60 groups were significantly lower than in the DIR group (p = 0.018 and p = 0.008, respectively). Furthermore, the levels of malondialdehyde (MDA) in the DIR-S, DIR-FC60, and DIR-S-FC60 groups were significantly lower than in the DIR group (p < 0.001, p < 0.001, and p < 0.001, respectively). Catalase (CAT) enzyme activity in the DIR-S, DIR-FC60, and DIR-S-FC60 groups was higher than in the DIR group (p = 0.001, p = 0.014, and p < 0.001, respectively). Superoxide dismutase (SOD) enzyme activity in the DIR-FC60 and DIR-S-FC60 groups was also higher than in the DIR group (p < 0.001 and p = 0.001, respectively). CONCLUSION: Our findings indicate that administering fullerenol C60 30 min prior to ischemia in diabetic mice, in combination with sevoflurane, led to a reduction in oxidative stress and the correction of IR-related damage in muscle tissue histopathology. We believe that the administration of fullerenol C60 before IR, coupled with sevoflurane administration during IR, exerts a protective effect in mice.


Subject(s)
Diabetes Mellitus, Experimental , Fullerenes , Reperfusion Injury , Animals , Mice , Sevoflurane , Streptozocin , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Ischemia , Reperfusion Injury/drug therapy , Lower Extremity
19.
Eur J Med Chem ; 271: 116398, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38614061

ABSTRACT

In contemporary studies, the predominant utilization of C60 derivatives pertains to their role as photosensitizers or agents that scavenge free radicals. The intriguing coexistence of these divergent functionalities has prompted extensive investigation into water-soluble fullerenes. The photodynamic properties of these compounds find practical applications in DNA cleavage, antitumor interventions, and antibacterial endeavors. Consequently, photodynamic therapy is progressively emerging as a pivotal therapeutic modality within the biomedical domain, owing to its notable levels of safety and efficacy. The essential components of photodynamic therapy encompass light of the suitable wavelength, oxygen, and a photosensitizer, wherein the reactive oxygen species generated by the photosensitizer play a pivotal role in the therapeutic mechanism. The remarkable ability of fullerenes to generate singlet oxygen has garnered significant attention from scholars worldwide. Nevertheless, the limited permeability of fullerenes across cell membranes owing to their low water solubility necessitates their modification to enhance their efficacy and utilization. This paper reviews the applications of fullerene derivatives as photosensitizers in antitumor and antibacterial fields for the recent years.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Fullerenes , Photochemotherapy , Photosensitizing Agents , Fullerenes/chemistry , Fullerenes/pharmacology , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Animals , Molecular Structure , Neoplasms/drug therapy
20.
Sci Total Environ ; 929: 172416, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38631627

ABSTRACT

Widespread use of copper-based agrochemical may cause copper excessive accumulation in agricultural soil to seriously threaten crop production. Recently, fullerenols are playing important roles in helping crops build resistance to abiotic stresses by giving ingenious and successful resolutions. However, there is a lack of knowledge on their beneficial effects in crops under stresses induced by heavy metals. Herein, the visual observation of Cu2+-mediated assembly of fullerenols via electrostatic and coordination actions was carried out in vitro, showing that water-soluble nanocomplexes and water-insoluble cross-linking nanohybrids were selectively fabricated by precisely adjusting feeding ratios of fullerenols and CuSO4. Furthermore, maize simultaneous exposure of fullerenols and CuSO4 solutions was tested to investigate the comparative effects of seed germination and seedling growth relative to exposure of CuSO4 alone. Under moderate Cu2+ stresses (40 and 80 µM), fullerenols significantly mitigated the detrimental effects of seedlings, including phenotype, root and shoot elongation, biomass accumulation, antioxidant capacity, and Cu2+ uptake and copper transporter-related gene expressions in roots. Under 160 µM of Cu2+ as a stressor, fullerenols also accelerated germination of Cu2+-stressed seeds eventually up to the level of the control. Summarily, fullerenols can enhance tolerance of Cu2+-stressed maize mainly due to direct detoxification through fullerenol-Cu2+ interactions restraining the Cu2+ intake into roots and reducing free Cu2+ content in vivo, as well as fullerenol-maize interactions to enhance resistance by maintaining balance of reactive oxygen species and optimizing the excretion and transport of Cu2+. This will unveil valuable insights into the beneficial roles of fullerenols and its mechanism mode in alleviating heavy metal stress on crop plants.


Subject(s)
Copper , Seedlings , Zea mays , Zea mays/drug effects , Zea mays/physiology , Copper/toxicity , Seedlings/drug effects , Soil Pollutants , Fullerenes , Stress, Physiological , Germination/drug effects
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