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1.
Eur J Med Chem ; 271: 116398, 2024 May 05.
Article En | MEDLINE | ID: mdl-38614061

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.


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
2.
Cell Biochem Funct ; 42(2): e3963, 2024 Mar.
Article En | MEDLINE | ID: mdl-38424684

Mycobacterium tuberculosis and nontuberculous mycobacteria such as Mycobacterium abscessus cause diseases that are becoming increasingly difficult to treat due to emerging antibiotic resistance. The development of new antimicrobial molecules is vital for combating these pathogens. Carbon nanomaterials (CNMs) are a class of carbon-containing nanoparticles with promising antimicrobial effects. Fullertubes (C90 ) are novel carbon allotropes with a structure unique among CNMs. The effects of fullertubes on any living cell have not been studied. In this study, we demonstrate that pristine fullertube dispersions show antimicrobial effects on Mycobacterium smegmatis and M. abscessus. Using scanning electron microscopy, light microscopy, and molecular probes, we investigated the effects of these CNMs on mycobacterial cell viability, cellular integrity, and biofilm formation. C90 fullertubes at 1 µM inhibited mycobacterial viability by 97%. Scanning electron microscopy revealed that the cell wall structure of M. smegmatis and M. abscessus was severely damaged within 24 h of exposure to fullertubes. Additionally, exposure to fullertubes nearly abrogated the acid-fast staining property of M. smegmatis. Using SYTO-9 and propidium iodide, we show that exposure to the novel fullertubes compromises the integrity of the mycobacterial cell. We also show that the permeability of the mycobacterial cell wall was increased after exposure to fullertubes from our assays utilizing the molecular probe dichlorofluorescein and ethidium bromide transport. C90 fullertubes at 0.37 µM and C60 fullerenes at 0.56 µM inhibited pellicle biofilm formation by 70% and 90%, respectively. This is the first report on the antimycobacterial activities of fullertubes and fullerenes.


Anti-Infective Agents , Fullerenes , Fullerenes/pharmacology , Mycobacterium smegmatis , Anti-Infective Agents/pharmacology , Biofilms , Cell Wall
3.
ACS Appl Mater Interfaces ; 16(5): 5536-5547, 2024 Feb 07.
Article En | MEDLINE | ID: mdl-38267397

Autoimmune hepatitis (AIH) is a severe immune-mediated inflammatory liver disease whose standard of care is immunosuppressive treatment with inevitable undesired outcomes. Macrophage is acknowledged to aggravate liver damage, providing a promising AIH therapeutic target. Accordingly, in this study, a kind of curdlan-decorated fullerene nanoparticle (Cur-F) is fabricated to alleviate immune-mediated hepatic injury for treating AIH via reducing macrophage infiltration in a concanavalin A (Con A)-induced AIH mouse model. After intravenous administration, Cur-F primarily distributes in liver tissues, efficiently eliminates the excessive reactive oxygen species, significantly attenuates oxidative stress, and subsequently suppresses the nuclear factor kappa-B-gene binding (NF-κB) signal pathway, resulting in the lowered production of pro-inflammatory cytokines and the balancing of the immune homeostasis with the prevention of macrophage infiltration in the liver. The regulation of hepatic inflammation contributes to inhibiting inflammatory cytokines-induced hepatocyte apoptosis, decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents and thus ameliorating immune-mediated hepatic injury. Notably, there is no detectable toxicity to the body. Our findings may open up novel avenues for AIH based on curdlan and fullerene materials.


Fullerenes , Hepatitis, Autoimmune , beta-Glucans , Animals , Mice , Hepatitis, Autoimmune/drug therapy , Hepatitis, Autoimmune/metabolism , Fullerenes/pharmacology , Fullerenes/therapeutic use , Fullerenes/metabolism , Liver/metabolism , Cytokines/metabolism , NF-kappa B/metabolism , Concanavalin A , Macrophages/metabolism
4.
Photodiagnosis Photodyn Ther ; 45: 103926, 2024 Feb.
Article En | MEDLINE | ID: mdl-38065228

AIM: Assessment of the impact of contemporary disinfection techniques Moringa Oleifera (M. Oleifera), NanoCare Plus Silver Gold® (Nanocare), and Fullerene (C60) on survival rates of S.Mutans and shear bond strength (SBS) of composite to the carious affected dentin (CAD) MATERIAL AND METHODS: Sixty mandibular molars having caries progression till the middle 1/3rd of the dentin were disinfected. The CAD surface of twenty samples was inoculated with S.mutans. Based on different disinfection regimens samples were arbitrarily assigned to four groups (n:15) Group 1: 2 % CHX, Group 2:NanoCare, Group 3:Fullerene (C60), and Group 4 (M. Oleifera. This was followed by calculating the survival rate of S.mutans. Ten samples from each group were then restored with composite restoration and thermocycled. Assessment of SBS and failure mode was performed using a universal testing machine and stereomicroscope at 40X magnification. Statistical significance among groups was assessed using analysis of variance (ANOVA) and Tukey's test at a significance level of p = 0.05 RESULTS: Group 2 samples treated with NanoCare exhibited the lowest survival rate (0.39 ± 0.02 CFU/ml) of S.Mutans. However, Group 1 (CHX) samples exhibited the highest survival count (0.51±0.10 CFU/ml). Furthermore, the highest composite to CAD bond was observed in Group 3 Fullerene(C60) (18.44±0.25 MPa) samples and the lowest SBS was observed in Group 1 (CHX) (12.48±1.69 MPa) CONCLUSION: Fullerene(C60) and Moringa Oleifera extract hold promise as potential substitutes for chlorhexidine (CHX) in clinical applications, offering the potential for improved S.Mutans elimination and enhanced bond strength to CAD surface.


Fullerenes , Morinda , Photochemotherapy , Composite Resins/chemistry , Dentin , Ultraviolet Rays , Dental Caries Susceptibility , Fullerenes/pharmacology , Fullerenes/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Chlorhexidine/therapeutic use , Anti-Bacterial Agents/therapeutic use
5.
Reprod Domest Anim ; 59(1): e14513, 2024 Jan.
Article En | MEDLINE | ID: mdl-38038214

This study aimed to investigate the morphological, functional and molecular changes in frozen-thawed ram sperm using an extender containing different concentrations of hydrated carbon 60 fullerene (C60 HyFn), a nanotechnological product. Semen taken from each of the seven Akkaraman rams were pooled. Semen collection was done twice a week and it continued for 3 weeks. Each pooled semen sample was divided into six equal groups and diluted with tris + egg yolk extender including 0 (control), 200, 400, 800 nM, 1 and 5 µM concentrations of C60 HyFn at 37°C. They were then frozen in liquid nitrogen vapour at -140°C, stored in liquid nitrogen container (-196°C) and thawed at 37°C for 25 s before analysis. In comparison with control, C60 HyFn addition prior to freezing procedure provided significant increases in total and progressive motility rates, glutathione peroxidase, catalase activities and percentage of highly active mitochondria, and significant decreases in dead and abnormal sperm rates, lipid peroxidation, caspase-3 and DNA fragmentation levels in frozen-thawed ram semen. When compared to control, C60 HyFn supplementation significantly down-regulated the expression levels of miR-200a and KCNJ11, and significantly up-regulated the expression levels of miR-3958-3p (at the concentrations of 200, 400, 800 nM and 1 µM), CatSper1 (at the concentrations of 200, 400 nM and 5 µM), CatSper2 (at the concentrations of 1 and 5 µM), CatSper3 (at the concentrations of 200, 400 nM, 1 and 5 µM), CatSper4 (at all concentrations), ANO1 (at the concentrations of 800 nM, 1 and 5 µM) and TRPV5 (at the concentrations of 200, 400 and 800 nM). The addition of C60 HyFn had no effect on global DNA methylation rates. As a result, C60 HyFn supplementation to ram semen extenders may be beneficial in reducing some of the functional, structural and molecular damages in sperm induced by the freeze-thawing procedure.


Fullerenes , MicroRNAs , Semen Preservation , Male , Sheep , Animals , Semen , Fullerenes/pharmacology , Sperm Motility , Cryoprotective Agents/pharmacology , Spermatozoa , Cryopreservation/veterinary , Cryopreservation/methods , Sheep, Domestic , Semen Preservation/veterinary , Semen Preservation/methods , Nitrogen/pharmacology
6.
Small ; 20(19): e2307045, 2024 May.
Article En | MEDLINE | ID: mdl-38100142

Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry. Among others, C-type lectins such as DC-SIGN are identified as efficient trans-receptor for SARS-CoV-2 infection, so the use of glycomimetics to inhibit the infection through the DC-SIGN blockade is an encouraging approach. In this regard, multivalent nanostructures based on glycosylated [60]fullerenes linked to a central porphyrin scaffold have been designed and tested against DC-SIGN-mediated SARS-CoV-2 infection. First results show an outstanding inhibition of the trans-infection up to 90%. In addition, a deeper understanding of nanostructure-receptor binding is achieved through microscopy techniques, high-resolution NMR experiments, Quartz Crystal Microbalance experiments, and molecular dynamic simulations.


Cell Adhesion Molecules , Fullerenes , Lectins, C-Type , Porphyrins , Receptors, Cell Surface , SARS-CoV-2 , SARS-CoV-2/drug effects , Lectins, C-Type/metabolism , Lectins, C-Type/antagonists & inhibitors , Humans , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/antagonists & inhibitors , Receptors, Cell Surface/metabolism , Receptors, Cell Surface/antagonists & inhibitors , Fullerenes/chemistry , Fullerenes/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/chemistry , COVID-19/virology , Protein Binding , Molecular Dynamics Simulation , COVID-19 Drug Treatment
7.
Proc Natl Acad Sci U S A ; 120(52): e2311673120, 2023 Dec 26.
Article En | MEDLINE | ID: mdl-38109541

The unbalanced immune state is the dominant feature of myocardial injury. However, the complicated pathology of cardiovascular diseases and the unique structure of cardiac tissue lead to challenges for effective immunoregulation therapy. Here, we exploited oral fullerene nanoscavenger (OFNS) to maintain intestinal redox homeostasis to resolve systemic inflammation for effectively preventing distal myocardial injury through bidirectional communication along the heart-gut immune axis. Observably, OFNS regulated redox microenvironment to repair cellular injury and reduce inflammation in vitro. Subsequently, OFNS prevented myocardial injury by regulating intestinal redox homeostasis and recovering epithelium barrier integrity in vivo. Based on the profiles of transcriptomics and proteomics, we demonstrated that OFNS balanced intestinal and systemic immune homeostasis for remote cardioprotection. Of note, we applied this principle to intervene myocardial infarction in mice and mini-pigs. These findings highlight that locally addressing intestinal redox to inhibit systemic inflammation could be a potent strategy for resolving remote tissue injury.


Fullerenes , Myocardial Infarction , Swine , Mice , Animals , Fullerenes/pharmacology , Swine, Miniature , Inflammation/pathology , Myocardial Infarction/prevention & control , Homeostasis , Intestinal Mucosa
8.
Sci Rep ; 13(1): 21045, 2023 11 29.
Article En | MEDLINE | ID: mdl-38030752

The current prevalence of cancerous diseases necessitates the exploration of materials that can effectively treat these conditions while minimizing the occurrence of adverse side effects. This study aims to identify materials with the potential to inhibit the metastasis of cancerous diseases within the human body while concurrently serving as therapeutic agents for their treatment. A novel approach was employed to enhance the anti-cancer properties of electrospun cellulose fibers by incorporating fullerene nanoparticles (NPs) into cellulose acetate (CA) fibers, resulting in a composite material called Fullerene@CA. This development aimed at utilizing the anti-cancer properties of fullerenes for potential therapeutic applications. This process has been demonstrated in vitro against various types of cancer, and it was found that Fullerene@CA nanocomposite fibers displayed robust anticancer activity. Cancer cells (Caco-2, MDA-MB 231, and HepG-2 cells) were inhibited by 0.3 and 0.5 mg.g-1 fullerene doses by 58.62-62.87%, 47.86-56.43%, and 48.60-57.73%, respectively. The tested cancer cells shrink and lose their spindle shape due to morphological changes. The investigation of the prepared nanocomposite reveals its impact on various genes, such as BCL2, NF-KB, p53, Bax, and p21, highlighting the therapeutic compounds' effectiveness. The experimental results demonstrated that the incorporation of NPs into CA fibers resulted in a significant improvement in their anti-cancer efficacy. Therefore, it is suggested that these modified fibers could be utilized as a novel therapeutic approach for the treatment and prevention of cancer metastasis.


Fullerenes , Nanocomposites , Neoplasms , Humans , Fullerenes/pharmacology , Fullerenes/therapeutic use , Caco-2 Cells , Cellulose
9.
Int J Mol Sci ; 24(19)2023 Sep 23.
Article En | MEDLINE | ID: mdl-37833919

The disease of SARS-CoV-2 has caused considerable morbidity and mortality globally. Spike proteins on the surface of SARS-CoV-2 allow it to bind with human cells, leading to infection. Fullerenes and their derivatives are promising SARS-CoV-2 inhibitors and drug-delivery vehicles. In this study, Gaussian accelerated molecular dynamics simulations and the Markov state model were employed to delve into the inhibitory mechanism of Fullerene-linear-polyglycerol-b-amine sulfate (F-LGPS) on spike proteins. During the study, it was discovered that fullerene derivatives can operate at the interface of the receptor-binding domain (RBD) and the N-terminal domain (NTD), keeping structural domains in a downward conformation. It was also observed that F-LGPS demonstrated superior inhibitory effects on the XBB variant in comparison to the wild-type variant. This study yielded invaluable insights for the potential development of efficient therapeutics targeting the spike protein of SARS-CoV-2.


COVID-19 , Fullerenes , Humans , SARS-CoV-2 , Fullerenes/pharmacology , Spike Glycoprotein, Coronavirus , Molecular Dynamics Simulation , Protein Binding
10.
Environ Sci Pollut Res Int ; 30(54): 115896-115906, 2023 Nov.
Article En | MEDLINE | ID: mdl-37897582

The extensive application of carbon nanomaterials (CNMs) has attracted increasing studies concerned about its environmental impact. These studies focus on single exposure to CNMs, but repeated exposures with relatively low concentration are more likely to occur under actual exposure scenario. In this study, we studied the metabolic functional and structure of soil microorganism community under single and repeated exposures to multiwalled carbon nanotubes (MW), graphene (GR), and fullerene (C60) by Biolog EcoPlates and high-throughput sequencing. Our findings revealed that repeated exposures to CNMs significantly increase the metabolic activity and diversity of the soil microbial community as compared with single exposure. Principal component and similarity analysis not only indicated that GR exerted a stronger effect on soil microbial diversity among three exposures compared to C60 and MW, but also revealed that the metabolic activity of the soil microbial community was more affected by the exposure scenarios of CNMs than the type of CNMs. These findings elucidated the effect of CNMs under different exposure scenarios on soil microorganism community, providing a new perspective on the risk assessment of nanomaterials.


Fullerenes , Graphite , Microbiota , Nanostructures , Nanotubes, Carbon , Soil/chemistry , Nanotubes, Carbon/chemistry , Fullerenes/pharmacology , Nanostructures/chemistry , Graphite/chemistry , Soil Microbiology
11.
Plant Physiol Biochem ; 204: 108095, 2023 Nov.
Article En | MEDLINE | ID: mdl-37866064

Copper (Cu), when in excess, is one of the most toxic and hazardous metals to all living organisms, including plants. Engineered nanomaterials have the potential for increasing crop protection. However, the protective role of fullerenes (carbon-based nanoparticles with wide application in various areas) against Cu toxicity in plants is, so far, understudied. The present study investigated whether fullerenes can potentially alleviate Cu toxicity in plants (Cucumis sativus L.). Two water-soluble fullerene C60 derivatives were examined: fullerenol [C60(OH)22-24] and arginine-functionalized fullerene [C60(C6H13N4O2)8H8], under controlled conditions using hydroponics. Plants treated with 15 µM of Cu exhibited typical symptoms of Cu toxicity: impaired growth, leaf chlorosis, reduced photosynthetic activity, nutritional imbalances, and enhanced lipid peroxidation. These symptoms were alleviated in the presence of fullerene derivatives with arginine C60 having the more pronounced effect. Improved cucumber Cu tolerance was attributable to Cu buffering in the root zone (roots and medium), which caused a dramatic decline in Cu transport towards leaves and the elimination of oxidative damage. The Cu removal efficacy of arginine C60 was much greater than that of fullerenol. These fullerenes acted in a dose-dependent manner and removed Cu selectively without significant modification of the bioavailability of other essential nutrients. Treatment with free arginine did not affect Cu immobilization or Cu toxicity. These results suggest that the surface chemistry of the fullerene core is important for the protection of plants under excessive Cu conditions. The information offered a new approach to preparing promising practical materials for alleviating Cu toxicity in plants with potential application in fields.


Cucumis sativus , Fullerenes , Copper/toxicity , Fullerenes/pharmacology , Water/chemistry
12.
ChemMedChem ; 18(20): e202300296, 2023 10 17.
Article En | MEDLINE | ID: mdl-37728195

Monoderivatives of fullerenes functionalized with hydrophilic groups make them water soluble, while preserving the hydrophobic fullerene cage. This class of molecules have intriguing biomedical applications, including drug delivery, photodynamic therapy (PDT), antiviral and antimicrobial activity and reactive oxygen species (ROS)-scavenging abilities. In this Concept we discuss the synthesis and biomedical applications of water-soluble fullerene monoderivatives and their biological behavior based on their structures.


Fullerenes , Photochemotherapy , Fullerenes/pharmacology , Fullerenes/chemistry , Fullerenes/therapeutic use , Water/chemistry , Reactive Oxygen Species , Drug Delivery Systems
13.
Adv Healthc Mater ; 12(29): e2300819, 2023 11.
Article En | MEDLINE | ID: mdl-37698231

Radiation-induced heart disease is a serious side effect of radiation therapy that can lead to severe consequences. However, effective and safe methods for their prevention and treatment are presently lacking. This study reports the crucial function of fullerenols in protecting cardiomyocytes from radiation injury. First, fullerenols are synthesized using a simple base-catalyzed method. Next, the as-prepared fullerenols are applied as an effective free radical scavenger and broad-spectrum antioxidant to protect against X-ray-induced cardiomyocyte injury. Their ability to reduce apoptosis via the mitochondrial signaling pathway at the cellular level is then verified. Finally, it is observed in animal models that fullerenols accumulate in the heart and alleviate myocardial damage induced by X-rays. This study represents a timely and essential analysis of the prevention and treatment of radiological myocardial injury, providing new insights into the applications of fullerenols for therapeutic strategies.


Fullerenes , Radiation Injuries , Animals , Fullerenes/pharmacology , Fullerenes/therapeutic use , Antioxidants , Free Radical Scavengers , Myocytes, Cardiac
14.
Free Radic Res ; 57(5): 373-383, 2023 May.
Article En | MEDLINE | ID: mdl-37585732

The objective of this study was to evaluate the effect of fullerene C60 nanoparticles against 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tissue damage in rats. 60 Wistar albino (8 weeks old) female rats were assigned into four groups: Control Group (C), Fullerene C60, DMBA, and Fullerene C60+DMBA. The rats in the DMBA and Fullerene C60+DMBA groups were administered DMBA (45 mg/kg bw, oral gavage). The rats in Fullerene C60, and Fullerene C60+DMBA groups were administered with Fullerene C60 (1.7 mg/kg bw, oral gavage). Expression levels of cytochrome-C, caspase-3, beclin-1, IL-1α, HO-1 and p53 proteins in lung tissue were determined by western blotting, lipid peroxidation malondialdehyde (MDA) analyzes, glutathione (GSH), glutathione peroxidase (GSH-Px), catalase activity (CAT) and total protein levels were determined by spectrophotometer. In addition, lung tissues were evaluated by histopathologically. Fullerene C60 reduced the increasing of MDA and IL-1α protein expression levels and attenuated histopathological changes in lung. Moreover, fullerene C60 enhanced the protein expression of cytochrome-C, caspase-3, beclin-1, HO-1, and p53, which were decreased in the DMBA group. Fullerene C60 has strong biological activity that it might be an effective approach for lung damage.


Acute Lung Injury , Fullerenes , Rats , Female , Animals , Caspases/metabolism , Fullerenes/metabolism , Fullerenes/pharmacology , Beclin-1/metabolism , Beclin-1/pharmacology , Tumor Suppressor Protein p53/metabolism , Caspase 3/metabolism , Rats, Wistar , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Oxidative Stress , Apoptosis , Glutathione/metabolism , Signal Transduction , Autophagy , Cytochromes/metabolism , Cytochromes/pharmacology
15.
Nanomedicine ; 53: 102698, 2023 09.
Article En | MEDLINE | ID: mdl-37507062

The work aimed to investigate the biocompatibility and biological activity of the water-soluble fullerene adduct C60-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C60-Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C60-Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in Japan for the treatment of ischemic and haemorrhagic strokes.


Fullerenes , Ischemic Stroke , Nanostructures , Stroke , Humans , Antioxidants/pharmacology , Antioxidants/therapeutic use , Fullerenes/pharmacology , Fullerenes/therapeutic use , Fullerenes/chemistry , Water , Stroke/drug therapy , Ischemia , Arginine/therapeutic use
16.
BMC Musculoskelet Disord ; 24(1): 606, 2023 Jul 25.
Article En | MEDLINE | ID: mdl-37491190

BACKGROUND: Being a scavenger of free radicals, C60 fullerenes can influence on the physiological processes in skeletal muscles, however, the effect of such carbon nanoparticles on muscle contractility under acute muscle inflammation remains unclear. Thus, the aim of the study was to reveal the effect of the C60 fullerene aqueous solution (C60FAS) on the muscle contractile properties under acute inflammatory pain. METHODS: To induce inflammation a 2.5% formalin solution was injected into the rat triceps surae (TS) muscle. High-frequency electrical stimulation has been used to induce tetanic muscle contraction. A linear motor under servo-control with embedded semi-conductor strain gauge resistors was used to measure the muscle tension. RESULTS: In response to formalin administration, the strength of TS muscle contractions in untreated animals was recorded at 23% of control values, whereas the muscle tension in the C60FAS-treated rats reached 48%. Thus, the treated muscle could generate 2-fold more muscle strength than the muscle in untreated rats. CONCLUSIONS: The attenuation of muscle contraction force reduction caused by preliminary injection of C60FAS is presumably associated with a decrease in the concentration of free radicals in the inflamed muscle tissue, which leads to a decrease in the intensity of nociceptive information transmission from the inflamed muscle to the CNS and thereby promotes the improvement of the functional state of the skeletal muscle.


Fullerenes , Rats , Animals , Fullerenes/pharmacology , Rats, Wistar , Water , Muscle, Skeletal , Muscle Contraction , Pain/drug therapy , Inflammation/chemically induced , Inflammation/drug therapy , Isometric Contraction
17.
J Mater Chem B ; 11(31): 7401-7409, 2023 08 09.
Article En | MEDLINE | ID: mdl-37431674

Myelosuppression is a predominant side-effect of radiotherapy, which manifests as the lower activity of blood cell precursors in bone marrow. Though progress in anti-myelosuppression has been made by the application of growth factors e.g., the granulocyte colony-stimulating factor (G-CSF), the side-effects (e.g., bone-pain, liver injury, and lung toxicity) limit their applications in clinic. Herein, we developed a strategy of efficiently normalizing leukopoiesis using gadofullerene nanoparticles (GFNPs) against myelosuppression triggered by radiation. Specifically, GFNPs with high radical-scavenging abilities elevated the generation of leukocytes and alleviated the bone marrow's pathological state under myelosuppression. Notably, GFNPs potentiated the differentiation, development, and maturation of leukocytes (neutrophils, lymphocytes) in radiation bearing mice even better than what G-CSF did. In addition, GFNPs had little toxicity towards the main organs including the heart, liver, spleen, lung, and kidney. This work provides an in-depth understanding of how advanced nanomaterials mitigate myelosuppression by regulating leukopoiesis.


Bone Marrow , Fullerenes , Mice , Animals , Bone Marrow/pathology , Leukopoiesis , Granulocyte Colony-Stimulating Factor/pharmacology , Fullerenes/pharmacology
18.
Vopr Virusol ; 67(6): 516-526, 2023 02 07.
Article Ru | MEDLINE | ID: mdl-37264841

INTRODUCTION: A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid. MATERIALS AND METHODS: An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated. RESULTS: Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60. CONCLUSIONS: Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.


Fullerenes , Hepatitis C , Vaccines, DNA , Viral Hepatitis Vaccines , Mice , Animals , Hepacivirus , Fullerenes/pharmacology , Fullerenes/metabolism , Base Sequence , Amino Acids/genetics , Amino Acids/metabolism , Amino Acids/pharmacology , Mice, Inbred C57BL , Adjuvants, Immunologic/genetics , Immunity, Cellular , Recombinant Proteins/genetics , Mice, Inbred BALB C , Vaccines, DNA/genetics , Vaccines, DNA/pharmacology , Viral Hepatitis Vaccines/genetics , Viral Hepatitis Vaccines/pharmacology
19.
J Mater Chem B ; 11(25): 5882-5897, 2023 06 28.
Article En | MEDLINE | ID: mdl-37310404

As a typical inflammatory bowel disease (IBD), ulcerative colitis (UC) has become prevalent worldwide in recent years. Though several materials have been proved to be effective in reducing intestinal oxidative stress to alleviate UC symptoms, dependence on high doses of exogenous drugs amplifies their safety risk for patients. To address this challenge, an oral therapy based on colon-targeting delivery of low-dose rhamnolipid (RL)/fullerene (C60) nanocomposites has been reported. With high biocompatibility being verified, RL/C60 largely mitigated the inflammation of mice with colitis shortly after its oral administration. Not only this, but also the intestinal microbiome of diseased mice was remarkably restored to the near-healthy level by our composites. Specifically, RL/C60 significantly promoted the colonization of intestinal probiotics and suppressed the biofilm formation of pathogenic bacteria, which is beneficial for reshaping the intestinal barrier. A close relationship of cytokines and oxidoreductases levels with gut flora further revealed that a change in RL/C60-induced intestinal microecology effectively improved the organismal immune system, which can be considered important for long-time recovery from UC.


Colitis, Ulcerative , Fullerenes , Gastrointestinal Microbiome , Nanocomposites , Mice , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Fullerenes/pharmacology , Oxidative Stress
20.
Org Biomol Chem ; 21(23): 4810-4816, 2023 06 14.
Article En | MEDLINE | ID: mdl-37248815

Porphyrin-fullerene composite systems are attracting great attention as photodynamic agents; however, water-soluble derivatives are still scarce. Herein, we prepared noncovalently a lipid membrane-incorporated porphyrin-fullerene composite system with relative stability in aqueous solution. As in the case of porphyrin-fullerene composite systems in nonpolar solvents, efficient formation of singlet oxygen occurred via photoinduced energy transfer between porphyrin and fullerene as the predominant pathway in the photodynamic activity under the hydrophobic conditions of the lipid membranes, resulting in enhanced photodynamic activity toward Colon26 and HeLa cells compared with the individual porphyrin and fullerene components. Furthermore, the porphyrin-fullerene composite system exhibited high selectivity toward HeLa cells over normal mouse fibroblast L929 cells.


Fullerenes , Porphyrins , Animals , Mice , Humans , Porphyrins/pharmacology , Porphyrins/chemistry , Fullerenes/pharmacology , Fullerenes/chemistry , HeLa Cells , Energy Transfer , Lipids
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