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/químicaRESUMO
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 farmacológicoRESUMO
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 â¢DPPH, â¢OH and O2â¢-, 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 PartículaRESUMO
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/farmacologiaRESUMO
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 farmacológicoRESUMO
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 fármacosRESUMO
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.