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1.
Biointerphases ; 19(4)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39007691

RESUMO

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.


Assuntos
Materiais Biocompatíveis , Fulerenos , Raios Infravermelhos , Animais , Fulerenos/química , Fulerenos/farmacologia , Ratos , Materiais Biocompatíveis/química , Células PC12 , Neurônios/efeitos dos fármacos , Neurônios/efeitos da radiação , Cálcio/metabolismo , Cálcio/química
2.
Int J Nanomedicine ; 19: 6035-6055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911505

RESUMO

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.


Assuntos
Transtorno do Espectro Autista , Disfunção Cognitiva , Modelos Animais de Doenças , Proteína Duplacortina , Fulerenos , Camundongos Endogâmicos C57BL , Animais , Camundongos , Fulerenos/farmacologia , Fulerenos/química , Transtorno do Espectro Autista/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Masculino , Comportamento Social , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fármacos Neuroprotetores/farmacologia , Neurogênese/efeitos dos fármacos , Transtorno Autístico/tratamento farmacológico
3.
Biomed Pharmacother ; 176: 116828, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810406

RESUMO

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.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Fulerenos , Sistemas de Liberação de Fármacos por Nanopartículas , Fármacos Fotossensibilizantes , Fulerenos/química , Sistemas de Liberação de Fármacos por Nanopartículas/síntese química , Sistemas de Liberação de Fármacos por Nanopartículas/normas , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Neoplasias Colorretais/tratamento farmacológico , Aminoácidos/química , Fluoruracila/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Células HT29 , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Animais , Camundongos , Luz
4.
Int J Biol Macromol ; 271(Pt 2): 132399, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754684

RESUMO

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.


Assuntos
COVID-19 , Fulerenos , Simulação de Dinâmica Molecular , SARS-CoV-2 , Fulerenos/química , Fulerenos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Humanos , COVID-19/virologia , Membrana Celular/química , Membrana Celular/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , HIV/efeitos dos fármacos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia
5.
Sci Rep ; 14(1): 11988, 2024 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796555

RESUMO

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.


Assuntos
Portadores de Fármacos , Fluoruracila , Grafite , Azul de Metileno , Adsorção , Grafite/química , Azul de Metileno/química , Fluoruracila/química , Portadores de Fármacos/química , Modelos Teóricos , Algoritmos , Fulerenos/química , Carbono/química , Proflavina/química , Nanopartículas/química , Antibióticos Antineoplásicos/química , Antineoplásicos/química
6.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791388

RESUMO

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.


Assuntos
Sistemas de Liberação de Medicamentos , Ácido Fólico , Fulerenos , Povidona , Ácido Fólico/química , Ácido Fólico/farmacologia , Humanos , Povidona/química , Fulerenos/química , Fulerenos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Linhagem Celular Tumoral , Células A549 , Células HeLa , Tamanho da Partícula
7.
Eur J Med Chem ; 271: 116398, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38614061

RESUMO

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.


Assuntos
Antibacterianos , Antineoplásicos , Fulerenos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fulerenos/química , Fulerenos/farmacologia , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Estrutura Molecular , Neoplasias/tratamento farmacológico
8.
Sci Prog ; 107(2): 368504241239444, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38614462

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental , Fulerenos , Traumatismo por Reperfusão , Animais , Camundongos , Sevoflurano , Estreptozocina , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Isquemia , Traumatismo por Reperfusão/tratamento farmacológico , Extremidade Inferior
9.
Adv Mater ; 36(23): e2310875, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38450765

RESUMO

Photodynamic therapy (PDT) has been approved for clinic. However, powerless efficiency for deep hypoxic tumor therapy remains an enormous challenge for PDT. Herein, a hypoxia-sensitive nanotherapeutic system (FTCD-SRGD) based on fullerene (C70) and anoxic activating chemical prodrug tirapazamine (TPZ) is rationally designed for multimodal therapy of deep hypoxic tumors. To enhance the accumulation and achieve specific drug release in tumor, the FTCD-SRGD is modified with cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGDfK) peptide and disulfide bonds. With the exacerbated hypoxic microenvironment created by C70 consuming O2 for generating reactive oxygen species (ROS), TPZ is activated to produce toxic radical species to ablate deep tumors, which achieves a synergistic treatment of C70-mediated PDT and hypoxia-enhanced chemotherapy. Additionally, given this hypoxia-sensitive system-induced immunogenic cell death (ICD) activating anticancer cytotoxic T lymphocyte to result in more susceptible tumor to immunotherapy, FTCD-SRGD plus immune checkpoint inhibitor (anti-PD-L1) fully inhibit deep hypoxic tumors by promoting infiltration of effector T cells in tumors. Collectively, it is the first time to develop a multimodal therapy system with fullerene-based hypoxia-sensitive PS for deep tumors. The powerful multimodal nanotherapeutic system for combining hypoxia-enhanced PDT and immunotherapy to massacre deep hypoxic tumors can provide a paradigm to combat the present bottleneck of tumor therapy.


Assuntos
Fulerenos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Tirapazamina , Fulerenos/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Fotoquimioterapia/métodos , Camundongos , Linhagem Celular Tumoral , Tirapazamina/química , Tirapazamina/farmacologia , Humanos , Terapia Combinada , Microambiente Tumoral/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Hipóxia Tumoral/efeitos dos fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
10.
J Cosmet Dermatol ; 23(4): 1422-1428, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38404060

RESUMO

BACKGROUND: There are very few cosmetic ingredients that can target oil control and extend the wear time. Fullerenes have been reported to have excellent antioxidant capacity and a variety of biological activities, such as quenching free radicals, inhibiting lipid peroxidation, and promoting lipid flocculation. OBJECTIVE: The purpose of applying foundation makeup on the face is to make the skin color even, but the secretion and oxidation of skin oil will make the makeup mottled and dull. In order to solve this problem, a fullerene composite material that can directionally absorb oil and resist oil oxidation has been developed. METHODS: Fullerenes and hydroxyapatite composite was prepared by high pressure homogenization under alkaline condition. The indicated morphology and structure were characterized by SEM, UV-Vis, Raman, and XRD. The oil absorption capacity was determined by adding the C60-hydroxyapatite composite to a mixed solution of hexane and oil, shaking for 1 h, filtering, analyzed by GC-MS, and calculating the oil absorption by external standard method. Artificial sebum was prepared by adding different mass of water and oleic acid to screen the optimum ratio. C60-hydroxyapatite mixture and C60-hydroxyapatite composite were added to the artificial sebum to test the oil-absorbing capacity of the materials. The hydroxyl radical scavenging ability of C60-hydroxyapatite composite containing different fullerene contents was measured by X-band ESR spectroscopy, and the long-term radical scavenging ability of the composites was tested in comparison with VC. Antioxidant experiment is adding C60-hydroxyapatite composite material, and hydroxyapatite to oleic acid, then the UV light irradiation is aimed to accelerate the oxidation of oleic acid. Oleic acid act as a control group, and make the detection of oleic acid peroxide value after 7 days. The safety of the materials was tested by using culture media to soak the C60-hydroxyapatite composite for 24 h and then used to culture cells. RESULTS: The characterization of SEM, UV-Vis, Raman, and XRD showed that fullerene clusters were dispersed on the surface of hydroxyapatite stably, and they formed a stable composite. The adsorption rates of C60-hydroxyapatite composites for oleic acid, phenyl trimethicone, caprylic capric glyceride, isooctyl palmitate, mineral oil, olive oil, and dimethicone were 60.5%, 9.3%, 9.15%, 5.24%, 2.94%, 1.01%, and 0%, respectively. The flocculation amount of artificial sebum was 5.9 g per gram of C60-hydroxyapatite mixture and 24.2 g per gram of C60-hydroxyapatite composite. C60-hydroxyapatite composites have excellent quenching ability for hydroxyl radicals. When the fullerene content is 1, 2, 3, and 4 mg/kg, the quenching rates are 25.02%, 39.57%, 49.75%, and 62.24%, respectively. The quenching effect was enhanced with the increase of fullerene content, and it had strong long-term antioxidant properties. It can also be proved that C60-hydroxyapatite composites have strong antioxidant capacity through antioxidant experiments. The peroxide value of oleic acid on Day 0 was 2.8, and after 7 days of UV irradiation, the peroxide values of blank control, hydroxyapatite group, C60-hydroxyapatite composite containing 0.5% and 1% fullerenes four groups of materials were 8.02 meq O2/kg, 7.98 meq O2/kg, 7.11 meq O2/kg, and 6.87 meq O2/kg, respectively. The cell activity was 20.94% and 99.2% after the cells were cultured for 24 h using C60-hydroxyapatite composite and hydroxyapatite extracts, respectively, and the addition of fullerene was able to significantly increase the cell activity. CONCLUSION: Fullerene hydroxyapatite complex has excellent directional oil absorption characteristics, which can effectively remove free radicals and reduce skin oil oxidation.


Assuntos
Antioxidantes , Fulerenos , Humanos , Antioxidantes/farmacologia , Fulerenos/química , Ácido Oleico , Radicais Livres , Peróxidos , Hidroxiapatitas
11.
Adv Mater ; 36(21): e2312440, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38332741

RESUMO

Delayed re-epithelization and weakened skin contractions are the two primary factors that hinder wound closure in large-scale acute or chronic wounds. However, effective strategies for targeting these two aspects concurrently are still lacking. Herein, an antioxidative active-shrinkage hydrogel (AHF@AS Gel) is constructed that can integratedly promote re-epithelization and skin constriction to accelerate large-scale acute and diabetic chronic wound closure. The AHF@AS Gel is encapsulated by antioxidative amino- and hydroxyl-modified C70 fullerene (AHF) and a thermosensitive active shrinkage hydrogel (AS Gel). Specifically, AHF relieves overactivated inflammation, prevents cellular apoptosis, and promotes fibroblast migration in vitro by reducing excessive reactive oxygen species (ROS). Notably, the AHF@AS Gel achieved ≈2.7-fold and ≈1.7-fold better re-epithelization in acute wounds and chronic diabetic wounds, respectively, significantly contributing to the promotion of wound closure. Using proteomic profiling and mechanistic studies, it is identified that the AHF@AS Gel efficiently promoted the transition of the inflammatory and proliferative phases to the remodeling phase. Notably, it is demonstrated that AS Gel alone activates the mechanosensitive epidermal growth factor receptor/Akt (EGFR/Akt) pathway and promotes cell proliferation. The antioxidative active shrinkage hydrogel offers a comprehensive strategy for acute wound and diabetic chronic wound closure via biochemistry regulation integrating with mechanical forces stimulation.


Assuntos
Antioxidantes , Hidrogéis , Pele , Cicatrização , Hidrogéis/química , Antioxidantes/química , Antioxidantes/farmacologia , Animais , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Camundongos , Cicatrização/efeitos dos fármacos , Fulerenos/química , Fulerenos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Receptores ErbB/metabolismo , Reepitelização/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Movimento Celular/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apoptose/efeitos dos fármacos
12.
Mol Med Rep ; 29(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38334145

RESUMO

The aim of the present study was to examine the effect of fullerenol C60 on lung and kidney tissue in sevoflurane­treated rats with lower extremity ischemia­reperfusion (IR) injury. A total of 30 Wistar albino rats weighing 225­275 g were used and were equally divided into five groups (n=6/group): i) Sham; ii) IR; iii) IR­fullerenol C60 (IR­FUL); iv) IR­sevoflurane; and v) IR­fullerenol C60­sevoflurane (IR­FUL­SEVO). Fullerenol C60 was administered intraperitoneally prior to lower extremity IR induction and sevoflurane was administered during the IR injury. Subsequently, lung and kidney histopathological examinations, and serum biochemical analyses were performed. Lung tissue showed markedly increased congestion and neutrophil infiltration in the IR group compared with in the sham group, and notable decreases in congestion and neutrophil infiltration were observed in the treatment groups compared with in the IR group. In the histopathological evaluation of the kidney samples, vacuolization, loss of brush border in tubular epithelial cells, tubular epithelial loss and varying degrees of tubular damage were observed in all groups that underwent IR. There was a significant increase in the mean renal tubule injury score in all IR groups compared with that in the sham group. In addition, the mean kidney injury score was significantly lower in the IR­FUL and IR­FUL­SEVO groups than that in the IR group. It was observed that the expression levels of tumor necrosis factor­α, interleukin 1ß and intercellular adhesion molecule 1 in the lung and kidney tissues were increased following IR, and were decreased in the groups treated with fullerenol C60 and sevoflurane. Notably, it was determined that the reduction in cytokine expression was greatest in the IR­FUL group. When the oxidant status parameters in the lungs and kidneys were examined, thiobarbituric acid reactive substances levels, and catalase and glutathione S­transferase enzyme activities were significantly different in the groups receiving sevoflurane or fullerenol C60 treatment compared with those in the IR group. The present study demonstrated the protective effects of fullerenol C60 on the lung and kidney tissues of rats under sevoflurane anesthesia after establishment of lower extremity IR. The results of the present study showed that fullerenol C60 can reduce oxidative and histopathological damage in the lungs and kidneys following IR of the lower extremities.


Assuntos
Fulerenos , Pulmão , Traumatismo por Reperfusão , Ratos , Animais , Ratos Wistar , Sevoflurano/farmacologia , Pulmão/patologia , Rim/patologia , Traumatismo por Reperfusão/metabolismo , Isquemia/metabolismo , Extremidade Inferior
13.
Int J Mol Sci ; 25(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255765

RESUMO

The development of new nanocontainers for hydrophobic drugs is one of the most important tasks of drug delivery. Dendrimers with hydrophobic interiors and soluble terminal groups have already been used as drug carriers. However, the most convenient candidates for this purpose are peptide dendrimers since their interiors could be modified by hydrophobic amino acid residues with a greater affinity for the transported molecules. The goal of this work is to perform the first molecular dynamics study of the complex formation of fullerenes C60 and C70 with Lys-2Gly, Lys G2, and Lys G3 peptide dendrimers in water. We carried out such simulations for six different systems and demonstrated that both fullerenes penetrate all these dendrimers and form stable complexes with them. The density and hydrophobicity inside the complex are greater than in dendrimers without fullerene, especially for complexes with Lys-2Gly dendrimers. It makes the internal regions of complexes less accessible to water and counterions and increases electrostatic and zeta potential compared to single dendrimers. The results for complexes based on Lys G2 and Lys G3 dendrimers are similar but less pronounced. Thus, all considered peptide dendrimers and especially the Lys-2Gly dendrimer could be used as nanocontainers for the delivery of fullerenes.


Assuntos
Dendrímeros , Fabaceae , Fulerenos , Glicina , Lisina , Simulação de Dinâmica Molecular , Peptídeos , Água
14.
Int J Mol Sci ; 25(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255785

RESUMO

Gadolinium (Gd)-containing fullerenols are perspective agents for magnetic resonance imaging and cancer research. They combine the unique paramagnetic properties of Gd with solubility in water, low toxicity and antiradical activity of fullerenols. We compared the bioeffects of two Gd-containing fullerenols with a different number of oxygen groups-20 and 42: Gd@C82O20H14 and Gd@C82O42H32. The bioluminescent bacteria-based assay was applied to monitor the toxicity of fullerenols, bioluminescence was applied as a signal physiological parameter, and bacterial enzyme-based assay was used to evaluate the fullerenol effects on enzymatic intracellular processes. Chemiluminescence luminol assay was applied to monitor the content of reactive oxygen species (ROS) in bacterial and enzymatic media. It was shown that Gd@C82O42H32 and Gd@C82O20H14 inhibited bacterial bioluminescence at >10-1 and >10-2 gL-1, respectively, revealing a lower toxicity of Gd@C82O42H32. Low-concentration (10-3-10-1 gL-1) bacterial bioluminescence activation by Gd@C82O42H32 was observed, while this activation was not found under exposure to Gd@C82O20H14. Additional carboxyl groups in the structure of Gd@C82O42H32 were determined by infrared spectroscopy and confirmed by quantum chemical calculations. The groups were supposed to endow Gd@C82O42H32 with higher penetration ability through the cellular membrane, activation ability, lower toxicity, balancing of the ROS content in the bacterial suspensions, and lower aggregation in aqueous media.


Assuntos
Fulerenos , Gadolínio , Radioisótopos de Oxigênio , Oxigênio , Espécies Reativas de Oxigênio , Gadolínio/farmacologia , Bactérias
15.
ACS Appl Mater Interfaces ; 16(5): 5536-5547, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38267397

RESUMO

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.


Assuntos
Fulerenos , Hepatite Autoimune , beta-Glucanas , Animais , Camundongos , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/metabolismo , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Fulerenos/metabolismo , Fígado/metabolismo , Citocinas/metabolismo , NF-kappa B/metabolismo , Concanavalina A , Macrófagos/metabolismo
16.
Photodiagnosis Photodyn Ther ; 45: 103926, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065228

RESUMO

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.


Assuntos
Fulerenos , Morinda , Fotoquimioterapia , Resinas Compostas/química , Dentina , Raios Ultravioleta , Suscetibilidade à Cárie Dentária , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Clorexidina/uso terapêutico , Antibacterianos/uso terapêutico
17.
Artigo em Inglês | MEDLINE | ID: mdl-38063467

RESUMO

Nanotechnology has attained significant attention from researchers in past decades due to its numerous advantages, such as biocompatibility, biodegradability, and improved stability over conventional drug delivery systems. The fabrication of engineered nanoparticles (ENPs), including carbon nanotubes (CNTs), fullerenes, metallic and metal oxide-based NPs, has been steadily increasing day due to their wide range of applications from household to industrial applications. Fabricated ENPs can release different materials into the environment during their fabrication process. The effect of such materials on the environment is the primary concern with due diligence on the safety and efficacy of prepared NPs. In addition, an understanding of chemistry, reactivity, fabrication process, and viable mechanism of NPs involved in the interaction with the environment is very important. To date, only a limited number of techniques are available to assess ENPs in the natural environment which makes it difficult to ascertain the impact of ENPs in natural settings. This review extensively examines the environmental effects of ENPs and briefly discusses useful tools for determining NP size, surface charge, surface area, and external appearance. In conclusion, the review highlights the potential risks associated with ENPs and suggests possible solutions.


Assuntos
Fulerenos , Nanopartículas , Nanotubos de Carbono , Ecossistema , Nanotecnologia
18.
Sci Rep ; 13(1): 21045, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030752

RESUMO

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.


Assuntos
Fulerenos , Nanocompostos , Neoplasias , Humanos , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Células CACO-2 , Celulose
19.
Chem Commun (Camb) ; 59(91): 13551-13561, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37877250

RESUMO

Endohedral metallofullerenes (EMFs) offer a safe avenue to manipulate metals important to biomedical applications such as MRI contrast, X-ray contrast, radiolabeling, radiotherapy, chemotherapy, and the control of inflammation by scavenging reactive oxygen species (ROS). Moreover, functionalizing the double bonds on the surface of EMFs modifies their solubility, supramolecular behaviour, binding, targeting characteristics, and physical properties. While most existing water-soluble derivatives possess a statistical mixture of appended functional groups, progress has been made in creating molecularly-precise derivatives with a defined number of surface functional groups, leading to potentially more nuanced control of their behaviour and properties. Further elucidation of the structure-function relationships of these materials is expected to enhance their utility in biomedical applications and possibly broaden their use in diverse areas of science and technology.


Assuntos
Fulerenos , Fulerenos/química , Metais/química , Imageamento por Ressonância Magnética , Solubilidade
20.
Adv Healthc Mater ; 12(29): e2300819, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37698231

RESUMO

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.


Assuntos
Fulerenos , Lesões por Radiação , Animais , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Antioxidantes , Sequestradores de Radicais Livres , Miócitos Cardíacos
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