Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Theranostics ; 13(14): 4936-4951, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771782

RESUMO

Neuroinflammation is considered to drive the pathogenic process of neuronal degeneration in Parkinson's disease (PD). However, effective anti-neuroinflammation therapeutics for PD still remain dissatisfactory. Here we explore a robust therapeutic strategy for PD using anti-neuroinflammatory fullerenes. Methods: Oral fullerene was prepared by a ball-milling method. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was used to investigate the therapeutic effects and mechanisms of it. The gut microenvironment was evaluated by 16S rRNA gene sequencing, gas chromatography-mass spectrometry, quantitative polymerase chain reaction (Q-PCR), and western blot (WB). The neuroinflammation and neurodegeneration were evaluated by pathological analysis, Elisa kits, transmission electron microscopy, Q-PCR, WB and so on. Toxicity was assessed by weight, blood test and hematoxylin-eosin (HE) staining. Results: Oral fullerene therapeutic system that dissolved [60]fullerene into olive oil (abbreviated as OFO) was dexterously designed, which could reduce neuroinflammation via regulating the diversity of gut microbiome, increasing the contents of short chain fatty acids (SCFAs) and recovering the integrity of gut barrier. Accordingly, the reduction of neuroinflammation prevented dopaminergic neuronal degeneration. And thus, OFO significantly ameliorated motor deficits and fundamentally reversed dopamine (DA) loss in MPTP-induced PD mice. Of note, OFO exhibited low toxicity towards the living body. Conclusion: Our findings suggest that OFO is a safe-to-use, easy-to-apply, and prospective candidate for PD treatment in clinic, opening a therapeutic window for neuroinflammation-triggered neurodegeneration.

2.
Natl Sci Rev ; 10(12): nwad309, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38204453

RESUMO

Sleep deprivation (SD) is a severe public health threat that can cause systemic inflammation and nerve damage. Few effective and side-effect-free drugs are available to address SD. However, the bidirectional communications between the brain and gut provide new strategies for anti-SD therapeutics. Here we explored oral delivery of fullerene nano-antioxidants (FNAO) in the SD model to improve sleep by regulating abnormal intestinal barrier and systemic inflammation via the brain-gut axis. SD caused excessive reactive oxygen species (ROS) production and hyperactive inflammatory responses in the intestines of zebrafish and mouse models, leading to disturbed sleep patterns and reduced brain nerve activity. Of note, based on the property of the conjugated π bond of the C60 structure to absorb unpaired electrons, oral FNAO efficiently reduced the excessive ROS in the intestines, maintained redox homeostasis and intestinal barrier integrity, and ameliorated intestinal and systemic inflammation, resulting in superior sleep improvement. Our findings suggest that maintaining intestinal homeostasis may be a promising avenue for SD-related nerve injury therapy.

3.
Angew Chem Int Ed Engl ; 60(28): 15225-15229, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33855792

RESUMO

Inhaled gene therapy poses a unique potential of curing chronic lung diseases, which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically relevant gene transfer efficacy in the lung due to the presence of numerous biological delivery barriers. Here, we introduce a simple approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo. We endowed tetra(piperazino)fullerene epoxide (TPFE)-based nanoparticles with non-adhesive surface polyethylene glycol (PEG) coatings, thereby enabling the nanoparticles to cross the airway mucus gel layer and avoid phagocytic uptake by alveolar macrophages. In parallel, we utilized a hypotonic vehicle to facilitate endocytic uptake of the PEGylated nanoparticles by lung parenchymal cells via the osmotically driven regulatory volume decrease (RVD) mechanism. We demonstrate that this two-pronged delivery strategy provides safe, wide-spread and high-level transgene expression in the lungs of both healthy mice and mice with chronic lung diseases characterized by reinforced delivery barriers.


Assuntos
Compostos de Epóxi/química , Fulerenos/química , Técnicas de Transferência de Genes , Pneumopatias/terapia , Nanopartículas/química , Doença Crônica , Humanos , Pneumopatias/metabolismo
4.
Langmuir ; 37(8): 2740-2748, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33586439

RESUMO

Hydrophilic fullerene derivatives get notable performance in various biological applications, especially in cancer therapy and antioxidation. The biological behaviors of functional fullerenes are much dependent on their surface physicochemical properties. The excellent reactive oxygen species-scavenging capabilities of functional fullerenes promote their outstanding performances in inhibiting pathological symptoms associated with oxidative stress, including neurodegenerative diseases, cardiovascular diseases, acute and chronic kidney disease, and diabetes. Herein, fullerene derivatives with reversed surface charges in aqueous solutions are prepared: cationic C60-EDA and anionic C60-(EDA-EA). Under the driving force of membrane potential (negative inside) in the cell and mitochondria, C60-EDA is much rapidly taken in by cells and transported into mitochondria compared with C60-(EDA-EA) that is enriched in lysosomes. With high cellular uptake and mitochondrial enrichment, C60-EDA exhibits stronger antioxidation capabilities in vitro than C60-(EDA-EA), indicating its better performance in the therapy of oxidation-induced diseases. It is revealed that the cellular uptake rate, subcellular location, and intracellular antioxidation behavior of fullerene derivatives are primarily mediated by their surface charges, providing new strategies for the design of fullerene drugs and their biological applications.


Assuntos
Fulerenos , Antioxidantes/farmacologia , Organelas , Estresse Oxidativo , Espécies Reativas de Oxigênio
5.
Nanoscale ; 12(33): 17470-17479, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32808001

RESUMO

Chronic exposure to crystalline silica causes the development of silicosis, which is one of the most important occupational diseases worldwide. In the early stage of silicosis, inhaled silica crystals initiate oxidative stress, a cycle of persistent inflammation and lung injury. And it is crucial to prevent the deteriorative progression in the onset of the disease. Herein, we present a promising candidate for the treatment of crystalline silica-induced pulmonary inflammation, using a silicosis mouse model caused by intratracheal instillation based on local administration of ß-alanine and hydroxyl functionalized C70 fullerene nanoparticles (FNs). The results demonstrate that FNs could significantly alleviate inflammatory cells infiltration, lower the secretion of pro-inflammatory cytokines, and reduce the destruction of lung architecture stimulated by crystalline silica. Further investigations reveal that FNs could effectively inhibit the activation of NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome, and thus prevent the secretion of mature IL-1ß and neutrophil influx, deriving from the superior ROS scavenging capability. Importantly, FNs could not cause any obvious toxicity after pulmonary administration.


Assuntos
Fulerenos , Nanopartículas , Pneumonia , Silicose , Animais , Inflamação/tratamento farmacológico , Pulmão , Camundongos , Pneumonia/tratamento farmacológico , Dióxido de Silício , Silicose/tratamento farmacológico
6.
ACS Appl Bio Mater ; 3(1): 450-457, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35019461

RESUMO

Radiotherapy is the current frontline method for cancer treatment, while the severe systemic side effects (e.g., myelosuppression) limit its application because it generates excessive reactive oxygen species. Therefore, there is a pressing need to develop effective strategies for radiotherapy protection. Here, we explored a robust myelosuppressive protector using gadofullerene nanocrystals (GFNCs) to protect mice against radiation injury, which was induced by different doses of X-rays (3, 4.5, and 6 Gy). Our data show that the radiotherapy-induced myelosuppression was remarkably reduced by the high radical scavenging abilities of GFNCs. In addition, GFNCs could normalize the oxidative stress-related indexes, such as malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). Of note, GFNCs provided protection of the bone marrow in tumor-bearing mice without interfering with the antitumor properties of radiotherapy. Thus, GFNCs may play a promising role in radioprotection during radiotherapy.

7.
ACS Nano ; 13(8): 8597-8608, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31314991

RESUMO

Type 2 diabetes mellitus (T2DM) has been one of the most prevalent metabolic disorders. Nonetheless, the commonly used anti-T2DM drugs failed to substant to treat T2DM when anti-T2DM was withdrawn. Here we put forward a superior and sustainable anti-diabetic strategy using intraperitoneal administration of amino-acid-functionalized gadofullerene nanoparticles (GFNPs) in db/db diabetic mice. Highly accumulated in the pancreas and liver, GFNPs could prominently decrease hyperglycemia, along with permanently maintaining normal blood sugar levels in T2DM mice and even stopping administration. Importantly, GFNPs reversed the pancreas islets dysfunctions by reducing oxidative stress and inflammation responses and fundamentally normalized the insulin secretory function of the pancreas islets. Mechanistically, GFNPs improved hepatic insulin resistance by regulating glucose and lipid metabolism through the activation of IRS2/PI3K/AKT signal pathways, resulting in inhibiting gluconeogenesis and increasing glycogenesis in the liver. Additionally, GFNPs relieved hepatic steatosis in the liver, ultimately maintaining systemic glucose and lipid metabolic homeostasis without obvious toxicity. Together, GFNPs reverse the dysfunctions of the pancreas and improve hepatic insulin resistance, providing a promising approach for T2DM treatment.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fulerenos/farmacologia , Pâncreas/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Humanos , Resistência à Insulina/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos NOD , Pâncreas/metabolismo , Pâncreas/patologia
8.
ACS Appl Mater Interfaces ; 11(24): 21343-21352, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31140277

RESUMO

Water-soluble gadofullerene nanomaterials have been extensively investigated as magnetic resonance imaging (MRI) contrast agents, radical scavengers, sensitizers for photodynamic therapy, and inherent antineoplastic agents. Most recently, an alanine-modified gadofullerene nanoparticle (Gd@C82-Ala) with excellent anticancer activity has been reported; however, the absolute tumor uptake of Gd@C82-Ala is still far from being satisfactory, and its dynamic pharmacokinetics and long-term metabolic behaviors remain to be elucidated. Herein, Gd@C82-Ala was chemically modified with eight-arm polyethylene glycol amine to improve its biocompatibility and provide the active sites for the attachment of a tumor-homing ligand (cRGD) and positron emission tomography (PET) isotopes (i.e., 64Cu or 89Zr). The physical and chemical properties (e.g., size, surface functionalization condition, radiochemical stability, etc.) of functionalized Gd@C82-Ala were properly characterized. Also, its glioblastoma cell targeting capacity was evaluated in vitro by flow cytometry, confocal fluorescence microscopy, and dynamic cellular interaction assays. Because of the presence of gadolinium ions, the gadofullerene conjugates can act simultaneously as T1* MRI contrast agents and PET probes. Thus, the pharmacokinetic behavior of functionalized Gd@C82-Ala was investigated by PET/MRI, which combines the merits of high resolution and excellent sensitivity. The functionalized Gd@C82-Ala-PEG-cRGD-NOTA-64Cu (NOTA stands for 1,4,7-triazacyclononane-triacetic acid) demonstrated much higher accumulation in U87-MG tumor than its counterpart without cRGD attachment from in vivo PET observation, consistent with observation at the cellular level. In addition, Gd@C82-Ala-PEG-Df-89Zr (Df stands for desferrioxamine) was employed to investigate the metabolic behavior of gadofullerene conjugates in vivo for up to 30 days. It was estimated that nearly 70% of Gd@C82-Ala-PEG-Df-89Zr was excreted from the test subjects primarily through renal pathways within 24 h. With proper surface engineering, functionalized Gd@C82-Ala nanoparticles can show an improved accumulation in glioblastoma. Pharmacokinetic studies also confirmed the safety of this nanoplatform, which can be used as an image-guidable therapeutic agent for glioblastoma.


Assuntos
Glioblastoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Tomografia por Emissão de Pósitrons/métodos , Animais , Citometria de Fluxo , Fulerenos/química , Gadolínio/química , Humanos , Células MCF-7 , Camundongos , Microscopia Confocal
9.
Biomaterials ; 213: 119218, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31136911

RESUMO

Efficient treatment of primary tumor and preventing cancer metastasis present intriguing alternatives to cancer therapy. Herein, for the first time, we reported the photo-triggered nano-gadofullerene (Gd@C82-Ala, abbreviated Gd-Ala) induced malignant tumor vascular disruption by shortening the light interval between Gd-Ala administration and light illumination, where oxygen in blood vessels was employed efficiently to produce cytotoxic reactive oxygen species (ROS). The produced ROS could not only destroy the tumor cells but also devastate the vascular endothelial cells corresponding to the loss of intercellular junctions and vessels disruption. Notably, the irradiated Gd-Ala could enhance dendritic cells (DCs) maturation, which further secreted tumor necrosis factor-α (TNF-α) and interleukin-12 (IL)-12, and then activated T lymphocytes by up-regulation of cluster of differentiation CD4+ and CD8+ T lymphocytes. Furthermore, the down-regulation of matrix metalloprotein 2 (MMP2) and MMP9 also reduce the rate of tumor metastasis. This work explored a new biomedical application of gadofullerene, thereby providing a smart carbon nanomaterial candidate for tumor ablation and inhibition of cancer metastasis.


Assuntos
Antineoplásicos/farmacologia , Fulerenos/farmacologia , Neoplasias/tratamento farmacológico , Neovascularização Patológica , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Feminino , Fulerenos/química , Fulerenos/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Humanos , Sistema Imunitário , Interleucina-12/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Neoplasias/irrigação sanguínea , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
ACS Appl Mater Interfaces ; 11(16): 14597-14607, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30938506

RESUMO

Along with the rapid appearance of superbacteria with multidrug resistance, it is a challenge to develop new antibacterial materials to address this big issue. Herein, we report a novel amine group-modified fullerene derivative (C70-(ethylenediamine)8 abrr. C70-(EDA)8), which reveals a high performance in killing superbacteria, and most importantly, it shows negligible toxicity to the mammalian cells. The strong antibacterial ability of this material was attributed to its unique molecular structure. On one hand, amino groups on the EDA part make it easy to affix onto the outer membrane of multidrug resistance Escherichia coli by electrostatic interactions. On the other hand, the hydrophobic surface on the C70 part makes it easy to form a strong hydrophobic interaction with the inner membrane of bacteria. Finally, C70-(EDA)8 leads to the cytoplast leakage of superbacteria. In contrast, the C70-(EDA)8 is nontoxic for mammalian cells due to different distributions of the negative charges in the cell membrane. In vivo studies indicated that C70-(EDA)8 mitigated bacterial infection and accelerated wound healing by regulating the immune response and secretion of growth factors. Our amine group-based fullerene derivatives are promising for clinical treatment of wound infection and offer a new way to fight against the superbacteria.


Assuntos
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Escherichia coli , Escherichia coli/crescimento & desenvolvimento , Fulerenos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos , Animais , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Fulerenos/química , Fulerenos/farmacocinética , Fulerenos/farmacologia , Células HEK293 , Humanos , Masculino , Ratos , Ratos Wistar , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/metabolismo , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
11.
Sci Rep ; 8(1): 16573, 2018 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-30410075

RESUMO

Despite the great efforts for tumor therapy in the last decades, currently chemotherapy induced toxicity remains a formidable problem for cancer patients, and it usually prohibits the cancer therapy from successful completion due to severe side effects. In general, the main side effects of chemotherapeutic agents are from the as-produced reactive oxygen species (ROS) that not only harm the tumor cells but also damage the patients' organs. Here we report the application of amino acid derivatives of fullerene (AADF) in the chemotherapy which strongly scavenge the excess ROS to protect the tested mice against the chemotherapy-induced hepatotoxicity and cardiotoxicity. Two amino acids, i.e., L-lysine and ß-alanine were separately employed to chemically modify C70 fullerene, and L-lysine derivative of fullerene (C70-Lys) exhibits superior radical scavenging activity to ß-alanine derivative of C70 (C70-Ala). As expected, C70-Lys show much better protective effect than C70-Ala against the chemotherapy injuries in vivo, which is verified by various histopathological, haematological examinations and antioxidative enzyme studies. Moreover, the L-glutathione level is increased and the cytochrome P-450 2E1 expression is inhibited. They are potentially developed as promising bodyguards for chemotherapy protection.


Assuntos
Aminoácidos/química , Antineoplásicos/efeitos adversos , Cardiotoxicidade/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Sequestradores de Radicais Livres/administração & dosagem , Fulerenos/administração & dosagem , Animais , Citocromo P-450 CYP2E1/metabolismo , Doxorrubicina/efeitos adversos , Feminino , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Fulerenos/química , Fulerenos/farmacologia , Glutationa/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Lisina/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , beta-Alanina/química
12.
J Am Chem Soc ; 140(24): 7373-7376, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29799737

RESUMO

Reactive oxygen species (ROS) and glutathione (GSH) dual responsive nanoparticulate drug delivery systems (nano-DDSs) hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemo drugs in cancer theranosis. Herein, hydrogen peroxide (H2O2) and GSH dual responsive thioketal nanoparticle (TKN) was rationally designed for paclitaxel (PTX) delivery. Compared to other stimuli-sensitive nano-DDSs, this dual responsive DDS is not only sensitive to biologically relevant H2O2 and GSH for on-demand drug release but also biodegradable into biocompatible byproducts after fulfilling its delivering task. Considering the heterogeneous redox potential gradient, the PTX loaded TKNs (PTX-TKNs) might first respond to the extracellular ROS and then to the intracellular GSH, achieving a programmable release of PTX at the tumor site. The selective toxicity of PTX-TKNs to tumor cells with high levels of ROS and GSH was verified both in vitro and in vivo.


Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/toxicidade , Células CHO , Linhagem Celular Tumoral , Cricetulus , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Glutationa/química , Química Verde/métodos , Humanos , Peróxido de Hidrogênio/química , Masculino , Camundongos , Nanopartículas/toxicidade , Paclitaxel/química , Paclitaxel/farmacologia , Polímeros/síntese química , Polímeros/química , Polímeros/toxicidade , Sulfetos/síntese química , Sulfetos/química , Sulfetos/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Nanomedicine ; 14(4): 1361-1369, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29649591

RESUMO

Pulmonary fibrosis has become a fatal disease for its high incidence and few effective drugs available in clinic. In this study, gadofullerenol (GF-OH) and [70] fullerenol (C70-OH) nanoparticles (NPs) prepared by a one-pot reaction were designed as nanomedicines to treat this fatal disease. It was revealed that the inhalation of gadofullerenols and [70] fullerenols substantially alleviates the collagen deposition induced by acute lung injury. Based on detailed studies of oxidative stress parameters and transforming growth factor-ß1 (TGF-ß1), we demonstrated they owned the antioxidant and anti-inflammatory functions for the modulation of ROS-mediated inflammation process. Thus the therapeutic effect may be associated with synergistic mechanism of scavenging free radicals and indirectly modulating TGF-ß1 expression. Moreover, GF-OH NPs were observed to show the superiority to C70-OH NPs both in vitro and in vivo due to the structural distinction. These results suggest the inhalable fullerenols are highly potential for clinical therapy of pulmonary fibrosis.


Assuntos
Fulerenos/administração & dosagem , Fulerenos/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Bleomicina/toxicidade , Linhagem Celular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Biomaterials ; 163: 142-153, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29459323

RESUMO

The tumor vasculature with unique characteristics offers an attractive target for anti-cancer therapy. Herein, we put forward a novel antitumor therapeutic mechanism based on the gadofullerene nanocrystals (GFNCs), the agent we have previously shown to efficiently disrupt tumor vasculature by size-expansion with assistance of radiofrequency (RF). However, the tumor vascular disrupting mechanism of RF-assisted GFNCs treatment was not further studied. In the present work, a rapid tumor blood flow shutdown has been observed by the vascular perfusion imaging in vivo and vascular damages were evident 6 h after the RF-assisted GFNCs treatment. Importantly, a significant down-expression of tumor vascular endothelial cadherin (VE-cadherin) treated by RF-assisted GFNCs was further investigated, which caused vascular collapse, blood flow shut-down and subsequent tumor hemorrhagic necrosis. These findings set forth a systematic mechanism on the superior anti-tumor efficiency by RF-assisted GFNCs treatment.


Assuntos
Antineoplásicos/administração & dosagem , Vasos Sanguíneos/metabolismo , Fulerenos/administração & dosagem , Gadolínio/química , Nanopartículas/química , Animais , Antígenos CD/metabolismo , Antineoplásicos/química , Caderinas/metabolismo , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Fulerenos/química , Células Hep G2 , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/uso terapêutico , Tamanho da Partícula , Ondas de Rádio
15.
ACS Appl Mater Interfaces ; 9(41): 35539-35547, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28945341

RESUMO

Chemotherapy as a conventional cancer treatment suffers from critical systemic side effects, which is generally considered as the consequence of reactive oxygen species (ROS). Fullerenes have been widely studied for their excellent performance in radicals scavenging. In the present study, we report a solid-liquid reaction to synthesize fullerenols and their application as ROS scavengers in chemotherapy protection. The solid-liquid reaction is carried out without catalyst and suitable for mass production. The novel [60]/[70] fullerenols show a high stability in water, and the [70] fullerenols (C70-OH) exhibit radical scavenging capability superior to that of [60] fullerenols (C60-OH) in chemotherapy protection. The mouse model for single and reduplicative chemotherapy-induced liver injury demonstrates their protective effects in the chemotherapeutic process, which is confirmed by histopathological examinations and hematological index. The increase of the hepatic l-glutathione (GSH) level and downregulated expression of the cytochrome P-450 2E1 (CYP2E1) give the possible mechanism associated with the impact of fullerenols on the metabolism of doxorubicin. The novel fullerenols may be promising protective agents to satisfy the demand for future clinical chemotherapy.

16.
Biomaterials ; 133: 107-118, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28433934

RESUMO

Researchers have been puzzled of the therapy of malignant tumors and the current therapeutic strategies are always accompanied by toxicity or side effects. Developing efficient nanodrugs could reduce the dosage and greatly improve the therapeutic effects in cancer treatments. Here we initially reported a novel kind of gadofullerene nanoparticles functionalized with amino acid (ß-alanine), which exhibited a superior antitumor activity in hepatoma H22 models via a novel therapeutic mechanism. The involvement of ß-alanine improved the tumor inhibition rate up to 76.85% for a single treatment by strengthening the interaction with radiofrequency (RF) and extending blood circulation time. It realized a highly antivascular treatment to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels assisted by RF. In situ and real-time observation of the vascular change was conducted using the dorsal skin fold chamber model, which corresponded to the erythrocyte diapedesis in histopathological examination. The ultrastructural changes of vascular endothelial cells were further investigated by environmental scanning electron microscopy and transmission electron microscopy. Long-term toxicity evaluation showed that the GF-Ala nanoparticles could be eliminated from the mice after several days and no obvious toxicity was found to the main organs. All these encouraging results suggest GF-Ala nanoparticles are valuable for the significant therapeutic potential with high-efficacy and low-toxicity.


Assuntos
Alanina/química , Antinematódeos/química , Antinematódeos/uso terapêutico , Fulerenos/química , Gadolínio/química , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico
17.
Acta Biomater ; 51: 408-417, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28069503

RESUMO

The surface of the elytra in some species of aquatic beetles displays relatively low contact angles (CAs), even showing hydrophilic properties. In this study, we report on an observation that both sexes of Cybister chinensis beetle fresh elytral surface do not exhibit uniform CA, but rather a wettability gradient along the longitudinal axis in posterior direction. The wettability is very different between females and males due to the presence (female) or absence (male) of channels on the elytral surface. When a small drop of water touches the elytra surface, it tends to slide towards the anterior having a lower CA on the elytra. This gradient presumably supports a breathing-associated behavior of beetles in which they cause the tip of their abdomen to protrude into the surface of the water in order to collect an air bubble for oxygen uptake and, when floating on the surface, to keep the body inclined at a small angle to the water's surface with their heads immersed. STATEMENT OF SIGNIFICANCE: Hydrophobicity on surfaces is a fundamental property which has attracted great interest across all scientific disciplines, here we have demonstrated that the gradually changing chemistry of the elytral surface facilitates the tilted beetle posture on the water's surface. The mechanism of water interacting with the elytra demonstrated the most energetically favorable posture in the diving beetles. Surfaces with directional wetting properties that promote droplet drainage are of significant practical importance in many fields. The anisotropic topography and wetting properties of the elytra may inspire microfluidic devices for medical and robotic applications.


Assuntos
Ar , Estruturas Animais/fisiologia , Organismos Aquáticos/fisiologia , Besouros/fisiologia , Água/química , Estruturas Animais/ultraestrutura , Animais , Fenômenos Biomecânicos , Feminino , Masculino , Imagem Óptica , Espectrofotometria Infravermelho , Molhabilidade
18.
ACS Appl Mater Interfaces ; 8(39): 25770-25776, 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27610478

RESUMO

It is important to maintain a reactive oxygen species (ROS) balance in organisms; thus, a valid ROS scavenger with good biocompatibility is urgently required. To prepare a high-efficiency ROS scavenger, multiple ethylenediamine (EDA) groups are bonded for the first time to a metallofullerene Gd@C82 to obtain water-soluble Gd@C82-(EDA)8 nanoparticles (NPs) through a facile solid-liquid reaction. Gd@C82-(EDA)8 NPs with a relatively better conjugation possess an excellent capability to scavenge hydroxyl radicals. Moreover, Gd@C82-(EDA)8 NPs exhibited a remarkable cytoprotective effect against H2O2-induced injuries to human epidermal keratinocytes-adult (HEK-a) cells at a low concentration of 2.5 µM. In contrast, Gd@C82-(OH)26 NPs that modified with hydroxyls show an apparent protective effect at a much higher concentration of 40 µM. This outstanding cytoprotective performance of Gd@C82-(EDA)8 NPs is mainly attributed to their extremely high cellular uptake and comparably strong conjugation. Gd@C82-(EDA)8 NPs with good biocompatibility exhibit excellent ROS scavenging capability even at a significantly low concentration, which promotes its versatile applications in cosmetics and biomedicine.


Assuntos
Nanopartículas , Linhagem Celular , Etilenodiaminas , Fulerenos , Gadolínio , Humanos , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Água
19.
Adv Healthc Mater ; 5(17): 2283-94, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27385651

RESUMO

Nanocarbons such as carbon nanotubes, graphene derivatives, and carbon nanohorns have illustrated their potential uses as cancer theranostics owing to their intrinsic fluorescence or NIR absorbance as well as superior cargo loading capacity. However, some problems still need to be addressed, such as the fates and long-term toxicology of different nanocarbons in vivo and the improvement of their performance in various biomedical imaging-guided cancer therapy systems. Herein, a versatile and clearable nanocarbon theranostic based on carbon dots (CDs) and gadolinium metallofullerene nanocrystals (GFNCs) is first developed, in which GFNCs enhance the tumor accumulation of CDs, and CDs enhance the relaxivity of GFNCs, leading to an efficient multimodal imaging-guided photodynamic therapy in vivo without obvious long-term toxicity. Furthermore, biochemical analysis reveals that the novel nanotheranostic can harmlessly eliminate from the body in a reasonable period of time after exerting diagnostic and therapeutic function.


Assuntos
Carbono/química , Fulerenos/química , Nanopartículas/química , Fotoquimioterapia/métodos , Pontos Quânticos/química , Nanomedicina Teranóstica/métodos , Linhagem Celular , Humanos
20.
J Nanosci Nanotechnol ; 16(3): 2504-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27455662

RESUMO

A homogeneous C60 tri-diethyl malonate membrane was fabricated by a facile electro-spinning method. Comprehensive characterizations of its assembling structure, such as SEM, TEM, TGA, UV-vis, and FTIR, were carried out. Different fullerene derivatives show different assembling characters during the electrospining process. Notably, C60 tri-diethyl malonate with close-knite structures can form a stable structure after removing the assistant polymer of PVP. The antibacterial experiments of C60 tri-diethyl malonate membrane were performed, and the results revealed that this membrane owns excellent antibacterial activity.


Assuntos
Antibacterianos/farmacologia , Fulerenos/química , Malonatos/química , Membranas Artificiais , Antibacterianos/química , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA