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1.
ACS Chem Neurosci ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369236

RESUMO

Lanosterol, an amphipathic molecule, was discovered only very recently to effectively hinder the aggregation of lens proteins and dissolve the extremely stable fibrillar aggregates in cataracts. Here, we combined computational and experimental approaches to study how lanosterol disrupts the aggregation of another important peptide, amyloid-ß (Aß) peptide, associated with the Alzheimer's Disease (AD). Molecular dynamics simulations using the core amyloidogenic segment (KLVFFA) of Aß peptide revealed that lanosterol exhibits at least two types of inhibition mechanism on the self-assembly of Aß peptides. First, lanosterol entangles with peptides and forms a hydrophobic core with residues Phe-19 and Phe-20 in particular. Second, it interferes with the steric zipper interaction at the ß-sheet-ß-sheet interface. These simulation data suggest that lanosterol induces the unfolding of the Aß peptide and the separation of the ß-sheet layers. This predicted inhibition effect of lanosterol was then confirmed by an in vitro ThT fluorescence assay and AFM imaging. The cell toxicity assay also showed that the treatment of lanosterol indeed mitigates the cytotoxicity of the Aß peptide in PC-12 cells. Moreover, lanosterol shows a stronger suppression effect on Aß peptides' aggregation than cholesterol because of its higher hydrophobicity. This result establishes a foundation for the development of lanosterol-based potential therapies for AD and other protein conformational diseases.

2.
Nanoscale ; 11(4): 1827-1836, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30633285

RESUMO

A better understanding of interactions between metal-nanomaterial surfaces and biomolecules such as DNAs is critical for their biomedical applications. Here we investigated double-stranded DNA (dsDNA) adhering to palladium (Pd) nanosheets with two different exposed facets, {100} and {111}, using a combined computational and experimental approach. Different dsDNA binding modes on the two surfaces were observed, with a surprising "upright" conformation on Pd(100) and a "flat" conformation on Pd(111). Molecular dynamics simulations showed a stronger binding of the dsDNA on Pd(111) than Pd(100), which resulted in significant conformational changes and hydrogen bond breakage in the dsDNA on Pd(111). Further analyses revealed that the different binding strengths were caused by the number and arrangement of water molecules in the first solvation shell (FSS) of the two Pd surfaces. The water hydrogen bond network in the FSS of Pd(100) is compact and resists the embedding of dsDNA, while it is less compact on Pd(111), which allows penetration of dsDNA and its direct contact with Pd(111) surface atoms, thereby exhibiting stronger binding. Further free energy calculations with umbrella sampling supported these observations. Finally, these computational predictions on the adsorption capacity of dsDNA on Pd surfaces were confirmed by gel electrophoresis experiments.


Assuntos
DNA/química , Paládio/química , Células A549 , DNA/metabolismo , Humanos , Ligações de Hidrogênio , Microscopia Eletrônica de Transmissão , Simulação de Dinâmica Molecular , Propriedades de Superfície , Termodinâmica
3.
ACS Appl Mater Interfaces ; 11(5): 4858-4866, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30628779

RESUMO

Molybdenum disulfide (MoS2) nanosheets have received considerable interest due to their superior physicochemical performances to graphene nanosheets. As the lateral size and layer thickness decrease, the formed MoS2 quantum dots (QDs) show more promise as photocatalysts, endowing them with potential antimicrobial properties under environmental conditions. However, studies on the antibacterial photodynamic therapy of MoS2 QDs have rarely been reported. Here, we show that MoS2 QDs more effectively promote the creation and separation of electron-hole pair than MoS2 nanosheets, resulting in the formation of multiple reactive oxygen species (ROS) under simulated solar light irradiation. As a result, photoexcited MoS2 QDs show remarkably enhanced antibacterial activity, and the ROS-mediated oxidative stress plays a dominant role in the antibacterial mechanism. The in vivo experiments showed that MoS2 QDs are efficacious in wound healing under simulated solar light irradiation and exert protective effects on normal tissues, suggesting good biocompatibility properties. Our findings provide a full description of the photochemical behavior of MoS2 QDs and the resulting antibacterial activity, which might advance the development of MoS2-based nanomaterials as photodynamic antibacterial agents under environmental conditions.


Assuntos
Antibacterianos , Dissulfetos , Molibdênio , Pontos Quânticos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/química , Dissulfetos/farmacologia , Dissulfetos/toxicidade , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Molibdênio/química , Molibdênio/farmacologia , Molibdênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Processos Fotoquímicos , Pontos Quânticos/química , Pontos Quânticos/efeitos da radiação , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio , Infecção dos Ferimentos
4.
Nat Commun ; 9(1): 4861, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30451824

RESUMO

Intravenous pharmacological dose of ascorbate has been proposed as a potential antitumor therapy; however, its therapeutic efficacy is limited due to the slow autoxidation. Here, we report that palladium (Pd) nanocrystals, which possess intrinsic oxidase-like activity, accelerate the autoxidation of ascorbate, leading to the enhancement of its antitumor efficacy. The oxidase-like activity of Pd nanocrystals was facet-dependent, with the concave nanostructure enclosed by high-index facets catalyzing ascorbate autoxidation more efficiently than the planar nanostructure enclosed by low-index facets. Our first-principles calculations provide the underlying molecular mechanisms for the facet-dependent activation of O2 molecule and subsequent ascorbate oxidation. Further in vitro and in vivo assays demonstrate the enhancement of the antitumor efficacy of ascorbate with these Pd concave nanocubes. Our animal experiments also indicate the combined approach with both ascorbate and Pd concave nanocubes displays an even better efficacy than currently available clinical medicines, with no obvious cytotoxicity to normal cells.

5.
Biomater Sci ; 6(7): 1892-1898, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29870037

RESUMO

Nanocomposites for integrating imaging and therapy have attracted tremendous attention for biomedical applications. Herein, Fe@Bi2S3 nanocomposites modified with polyethylene glycol (PEG) molecules are fabricated for synergistic thermoradiotherapy. For such nanocomposites, Bi2S3 exhibits a strong absorbance in the near-infrared (NIR) region, which allows Bi2S3 to convert energy from light into heat for effective photothermal therapy (PTT), whereas Bi can also significantly enhance radio-mediated cell death induction as a radiotherapy sensitizer due to its high atomic number (high-Z). Most importantly, it is found that the combination of PTT and radiation therapy (RT), using PEGylated Fe@Bi2S3 nanocomposites, can bring a strong synergistic effect for the tumor treatment in in vitro and in vivo experiments. Besides, the magnetic Fe core and the Bi2S3 shell components endow this nanocomposite with an ability to serve as both a magnetic resonance imaging (MRI) and computed tomography (CT) contrast agent. Therefore, our work presents a new type of multifunctional nanocomposite with the potential for synergistic thermoradiotherapy and simultaneously MRI/CT imaging.


Assuntos
Bismuto/farmacologia , Terapia Combinada/métodos , Meios de Contraste/farmacologia , Nanocompostos/química , Polietilenoglicóis/química , Radiossensibilizantes/farmacologia , Sulfetos/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Meios de Contraste/síntese química , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/efeitos da radiação , Feminino , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos/uso terapêutico , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Nanocompostos/administração & dosagem , Nanocompostos/ultraestrutura , Radiossensibilizantes/síntese química , Sulfetos/síntese química , Nanomedicina Teranóstica/métodos , Tomografia Computadorizada por Raios X , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Terapia por Raios X
6.
Sci Rep ; 8(1): 6022, 2018 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-29662078

RESUMO

In rotifers, the costs of morphological defenses, especially the development of long spines, have been investigated for several decades. However, the obtained results were inconsistent and the underlying reasons were complicated. Investigations on more species might be helpful to find out the reasons. In the present study, Brachionus forficula was selected as the model organism. The differences in developmental durations, life-table demography, starvation resistant time and the competitive ability with Moina macrocopa were compared between B. forficula with long (LPS) and short (SPS) posterior spines. The results showed that LPS showed relatively longer durations of juvenile stage at 1.0 × 106, 2.0 × 106 and 4.0 × 106 cells/ml Scenedesmus obliquus, and longer embryo stage at 2.0 × 106 cells/ml S. obliquus than SPS. The intrinsic rate of population increase and net reproduction rate were lower in LPS than SPS, suggesting the energy input to reproduction decreased. The starvation resistant time was also reduced in LPS, in comparison to SPS, further supporting that LPS consumed more energy, which might be directed to the development of long spines. All these results revealed that LPS spent more energy for individual growth than SPS, which might be used to develop long spines. Moreover, the maximum population density and population growth rate of LPS were always lower than those of SPS, suggesting that LPS might have a weaker competition ability with M. macrocope than SPS.

7.
Nanomedicine (Lond) ; 13(7): 733-747, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29542368

RESUMO

AIM: To develop the potential application of carbon nanomaterials as antioxidants calls for better understanding of how the specific structure affects their antioxidant activity. MATERIALS & METHODS: Several typical carbon nanomaterials, including graphene quantum dots and fullerene derivatives were characterized and their radical scavenging activities were evaluated; in addition, the in vitro and in vivo radioprotection experiments were performed. RESULTS: These carbon nanomaterials can efficiently scavenge free radicals in a structure-dependent manner. In vitro assays demonstrate that administration of these carbon nanomaterials markedly increases the surviving fraction of cells exposed to ionizing radiation. Moreover, in vivo experiments confirm that their administration can also increase the survival rates of mice exposed to radiation. CONCLUSION: All results confirm that large, buckyball-shaped fullerenes show the strongest antioxidant properties and the best radioprotective efficiency. Our work will be useful in guiding the design and optimization of nanomaterials for potential antioxidant and radioprotection bio-applications.

8.
ACS Appl Mater Interfaces ; 10(10): 8443-8450, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29481051

RESUMO

While the antibacterial properties of silver nanoparticles (AgNPs) have been demonstrated across a spectrum of bacterial pathogens, the effects of AgNPs on the beneficial bacteria are less clear. To address this issue, we compared the antibacterial activity of AgNPs against two beneficial lactobacilli ( Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus casei) and two common opportunistic pathogens ( Escherichia coli and Staphylococcus aureus). Our results demonstrate that those lactobacilli are highly susceptible to AgNPs, while the opportunistic pathogens are not. Acidic environment caused by the lactobacilli is associated with the bactericidal effects of AgNPs. Our mechanistic study suggests that the acidic growth environment of lactobacilli promotes AgNP dissolution and hydroxyl radical (•OH) overproduction. Furthermore, increases in silver ions (Ag+) and •OH deplete the glutathione pool inside the cell, which is associated with the increase in cellular reactive oxygen species (ROS). High levels of ROS may further induce DNA damage and lead to cell death. When E. coli and S. aureus are placed in a similar acidic environment, they also become more susceptible to AgNPs. This study provides a mechanistic description of a pH-Ag+-•OH bactericidal pathway and will contribute to the responsible development of products containing AgNPs.

9.
Nanotoxicology ; 12(2): 185-200, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29338468

RESUMO

Due to its hydrophobicity and other unique physicochemical properties, graphene oxide (GO) has been extensively utilized in various biological applications. However, introducing nanomaterials into the biological environment may raise serious risk in terms of nanotoxicity, leading to some unintended changes to the structure and the function of other biomolecules. This study investigates the interaction of GO with the ubiquitin-proteasome system, one of the essential machineries in the cellular metabolism, using a combination of experimental and computational approaches. The experimental results show that GO could adsorb the 20S proteasome, causing a dose-dependent suppression of the proteolytic activity of proteasome. This adverse effect eventually disturbed other important cellular activities relevant to cell cycle and survival. Meanwhile, the molecular dynamics simulations revealed that when 20S proteasome was adsorbed onto the graphene surface, the central gate in the outer ring (α-subunit) for the entry and the exit of the peptide ligand to the protease active site was effectively blocked. These findings of GO induced functional disturbance of 20S proteasome provides a novel perspective to understand the molecular mechanism of GO's cytotoxicity, which might further promote applications of GO in potential therapies for various cancers due to the abnormal elevation of the relevant proteasome activities.

10.
Nat Commun ; 9(1): 129, 2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29317632

RESUMO

Noble metal-based nanomaterials have shown promise as potential enzyme mimetics, but the facet effect and underlying molecular mechanisms are largely unknown. Herein, with a combined experimental and theoretical approach, we unveil that palladium (Pd) nanocrystals exhibit facet-dependent oxidase and peroxidase-like activities that endow them with excellent antibacterial properties via generation of reactive oxygen species. The antibacterial efficiency of Pd nanocrystals against Gram-positive bacteria is consistent with the extent of their enzyme-like activity, that is {100}-faceted Pd cubes with higher activities kill bacteria more effectively than {111}-faceted Pd octahedrons. Surprisingly, a reverse trend of antibacterial activity is observed against Gram-negative bacteria, with Pd octahedrons displaying stronger penetration into bacterial membranes than Pd nanocubes, thereby exerting higher antibacterial activity than the latter. Our findings provide a deeper understanding of facet-dependent enzyme-like activities and might advance the development of noble metal-based nanomaterials with both enhanced and targeted antibacterial activities.


Assuntos
Antibacterianos/química , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Nanopartículas/química , Paládio/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Nanopartículas/metabolismo , Nanopartículas/ultraestrutura , Oxirredutases/metabolismo , Paládio/metabolismo , Paládio/farmacologia , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Theranostics ; 7(17): 4087-4098, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29158812

RESUMO

Nanotechniques that can improve the effectiveness of radiotherapy (RT) by integrating it with multimodal imaging are highly desirable. Results In this study, we fabricated Bi2S3 nanorods that have attractive features such as their ability to function as contrast agents for X-ray computed tomography (CT) and photoacoustic (PA) imaging as well as good biocompatibility. Both in vitro and in vivo studies confirmed that the Bi2S3 nanoagents could potentiate the lethal effects of radiation via amplifying the local radiation dose and enhancing the anti-tumor efficacy of RT by augmenting the photo-thermal effect. Furthermore, the nanoagent-mediated hyperthermia could effectively increase the oxygen concentration in hypoxic regions thereby inhibiting the expression of hypoxia-inducible factor (HIF-1α). This, in turn, interfered with DNA repair via decreasing the expression of DNA repair-related proteins to overcome radio-resistance. Also, RT combined with nanoagent-mediated hyperthermia could substantially suppress tumor metastasis via down-regulating angiogenic factors. Conclusion In summary, we constructed a single-component powerful nanoagent for CT/PA imaging-guided tumor radiotherapy and, most importantly, explored the potential mechanisms of nanoagent-mediated photo-thermal treatment for enhancing the efficacy of RT in a synergistic manner.


Assuntos
Bismuto/química , Meios de Contraste/química , Nanotubos/química , Radioterapia Guiada por Imagem/métodos , Sulfetos/química , Animais , Bismuto/uso terapêutico , Linhagem Celular Tumoral , Dano ao DNA/efeitos da radiação , Hipertermia Induzida/métodos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos Endogâmicos BALB C , Imagem Multimodal , Técnicas Fotoacústicas/métodos , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Sulfetos/uso terapêutico , Nanomedicina Teranóstica/métodos , Tomografia Computadorizada por Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Toxicol Environ Health A ; 80(23-24): 1321-1330, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29048996

RESUMO

It is well known that cigarette smoking (CS) and/or radon (Rn) induce malignant transformation in lung cells. To investigate the mechanisms underlying lung carcinogenesis induced by CS, Rn; or Rn followed by CS using BEAS-2B cell line derived from human bronchial epithelial cells. BEAS-2B cells were exposed to either Rn (20,000 Bq/m3) for 30 min or CS (20%) for 10 min or Rn followed by CS for 40 min. Global and gene-specific DNA methylation modifications were measured by microarray and methylation-specific polymerase chain reaction. Cell cycle and apoptosis were determined by flow cytometry, while soft agar colony formation was conducted to assess the characteristics of malignant transformation. Data demonstrated global hypomethylation as well as gene-specific DNA methylation alterations in all treatment groups compared to unexposed control cells. In addition, Rn and CS produced DNA hypermethylation of protein tyrosine phosphatase receptor type M and ectodysplasin A2 receptor, two genes related to malignant transformation. In all treatment conditions, cell proliferation and survival of malignant cells was increased, while apoptosis was initially first passage elevated but decreased at passages 5-15. Our results indicate that aberrant DNA methylation plays an important role in Rn- and/or CS-induced malignant transformation. In addition, BEAS-2B cell line may be used as an in vitro model to investigate mechanisms underlying malignant transformation induced by ambient environmental contaminants.


Assuntos
Poluentes Atmosféricos/toxicidade , Transformação Celular Neoplásica/efeitos dos fármacos , Metilação de DNA , Pulmão/efeitos dos fármacos , Radônio/toxicidade , Fumaça , Produtos do Tabaco/toxicidade , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Humanos , Pulmão/citologia
13.
Exp Ther Med ; 14(4): 2831-2838, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28966671

RESUMO

In view of the compelling anti-diabetic effects of gastric bypass surgery (GBS) in the treatment of morbid obesity, it is important to clarify its enhancing effect on pancreatic islets, which is closely linked with diabetes remission in obese patients, as well as the underlying mechanisms. The present study evaluated the effects of GBS on glycemic control and other pancreatic changes in db/db mice. The db/db mice were divided into Control, Sham and GBS group. A significant improvement in fasting plasma glucose levels and glucose intolerance were observed post-surgery. At 4 weeks after surgery, further noteworthy changes were observed in the GBS group, including improved islet structure (revealed by immunohistochemical analysis), enhanced insulin secretion, pancreatic hyperplasia and a marked increase in the ratio of ß-cells to non-ß endocrine cells. Furthermore, notable changes in the levels of Notch-1, pancreatic and duodenal homeobox 1 (PDX-1) and neurogenin 3 (Ngn3) were observed in the GBS group, indicating a potential role of Notch signaling in pancreatic islet regeneration after surgery. In addition, results obtained in PDX-1 knockout (KO), Notch-1 KO and Ngn3 KO mouse models with GBS suggested that elevated PDX-1 resulted in the inhibition of Notch-1, further facilitated Ngn3 and thus promoted pancreatic ß-cell regeneration after GBS. The present findings demonstrated that GBS in db/db mice resulted in pancreatic islet regeneration through the PDX-1/Notch-1/Ngn3 signaling pathway, which also reflected the important role of the gastrointestinal system in metabolism control.

14.
Environ Sci Technol ; 51(17): 10154-10161, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28771330

RESUMO

Before graphene derivatives can be exploited as next-generation antimicrobials, we must understand their behavior under environmental conditions. Here, we demonstrate how exposure to simulated sunlight significantly enhances the antibacterial activity of graphene oxide (GO) and reveal the underlying mechanism. Our measurements of reactive oxygen species (ROS) showed that only singlet oxygen (1O2) is generated by GO exposed to simulated sunlight, which contributes only slightly to the oxidation of antioxidant biomolecules. Unexpectedly, we find the main cause of oxidation is light-induced electron-hole pairs generated on the surface of GO. These light-induced electrons promote the reduction of GO, introducing additional carbon-centered free radicals that may also enhance the antibacterial activities of GO. We conclude that GO-mediated oxidative stress mainly is ROS-independent; simulated sunlight accelerates the transfer of electrons from antioxidant biomolecules to GO, thereby destroying bacterial antioxidant systems and causing the reduction of GO. Our insights will help support the development of graphene for antibacterial applications.


Assuntos
Antibacterianos/farmacologia , Grafite/farmacologia , Antibacterianos/química , Transporte de Elétrons , Elétrons , Grafite/química , Luz , Óxidos
15.
Adv Mater ; 29(34)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28714110

RESUMO

The development of a new generation of nanoscaled radiosensitizers that can not only enhance radiosensitization of tumor tissues, but also increase radioresistance of healthy tissue is highly desirable, but remains a great challenge. Here, this paper reports a new versatile theranostics based on poly(vinylpyrollidone)- and selenocysteine-modified Bi2 Se3 nanoparicles (PVP-Bi2 Se3 @Sec NPs) for simultaneously enhancing radiotherapeutic effects and reducing the side-effects of radiation. The as-prepared nanoparticles exhibit significantly enhanced free-radical generation upon X-ray radiation, and remarkable photothermal effects under 808 nm NIR laser irradiation because of their strong X-ray attenuation ability and high NIR absorption capability. Moreover, these PVP-Bi2 Se3 @Sec NPs are biodegradable. In vivo, part of selenium can be released from NPs and enter the blood circulation system, which can enhance the immune function and reduce the side-effects of radiation in the whole body. As a consequence, improved superoxide dismutase and glutathione peroxidase activities, promoted secretion of cytokines, increased number of white blood cell, and reduced marrow DNA suppression are found after radiation treatment in vivo. Moreover, there is no significant in vitro and in vivo toxicity of PVP-Bi2 Se3 @Sec NPs during the treatment, which demonstrates that PVP-Bi2 Se3 @Sec NPs have good biocompatibility.

16.
J Appl Toxicol ; 37(9): 1053-1064, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28337774

RESUMO

Although nanomaterials have the potential to improve human life, their sideline effects on human health seem to be inevitable and still are unknown. Some studies have investigated the genotoxicity of alumina nanoparticles (AlNPs); however, this effect is still unclear due to insufficient evaluation and conflicting results. Using a battery of standard genotoxic assays, the present study offers evidence of the genotoxicity associated with aluminum oxide (alumina) at NP sizes of 50 and 13 nm, when compared with bulk alumina (10 µm). The genotoxicity induced by alumina at bulk and NP sizes was evaluated with Ames test, comet test, micronucleus assay and sperm deformity test. The mechanism related to the induction of reactive oxygen species was explored as well. Our results showed that AlNPs (13 and 50 nm) were able to enter cells and induced DNA damage, micronucleus in bone marrow, sperm deformation and reactive oxygen species induction in a time-, dose- and size-dependent manner. Therefore, we conclude that AlNPs (13 and 50 nm), rather than bulk alumina, induce markers of genotoxicity in mice, with oxidative stress as a potential mechanism driving these genotoxic effects. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Óxido de Alumínio/toxicidade , Dano ao DNA/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Animais , Ensaio Cometa , Cricetinae , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Concentração Inibidora 50 , Pulmão/citologia , Pulmão/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Salmonella typhimurium/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia
17.
Small ; 13(3)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27762498

RESUMO

Graphene and graphene-based nanomaterials are broadly used for various biomedical applications due to their unique physiochemical properties. However, how graphene-based nanomaterials interact with biological systems has not been thoroughly studied. This study shows that graphene oxide (GO) nanosheets retard A549 lung carcinoma cell migration through nanosheet-mediated disruption of intracellular actin filaments. After GO nanosheets treatment, A549 cells display slower migration and the structure of the intracellular actin filaments is dramatically changed. It is found that GO nanosheets are capable of absorbing large amount of actin and changing the secondary structures of actin monomers. Large-scale all-atom molecular dynamics simulations further reveal the interactions between GO nanosheets and actin filaments at molecular details. GO nanosheets can insert into the interstrand gap of actin tetramer (helical repeating unit of actin filament) and cause the separation of the tetramer which eventually leads to the disruption of actin filaments. These findings offer a novel mechanism of GO nanosheet induced biophysical responses and provide more insights into their potential for biomedical applications.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Grafite/farmacologia , Óxidos/farmacologia , Células A549 , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Morte Celular/efeitos dos fármacos , Grafite/química , Humanos , Ligações de Hidrogênio , Simulação de Dinâmica Molecular , Óxidos/química
18.
ACS Nano ; 10(11): 10436-10445, 2016 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-27934089

RESUMO

To develop nanomaterials as artificial enzymes, it is necessary to better understand how their physicochemical properties affect their enzyme-like activities. Although prior research has demonstrated that nanomaterials exhibit tunable enzyme-like activities depending on their size, structure, and composition, few studies have examined the effect of surface facets, which determine surface energy or surface reactivity. Here, we use electron spin-resonance spectroscopy to report that lower surface energy {111}-faceted Pd octahedrons have greater intrinsic antioxidant enzyme-like activity than higher surface energy {100}-faceted Pd nanocubes. Our in vitro experiments found that those same Pd octahedrons are more effective than Pd nanocubes at scavenging reactive oxygen species (ROS). Those reductions in ROS preserve the homogeneity of mitochondrial membrane potential and attenuate damage to important biomolecules, thereby allowing a substantially higher number of cells to survive oxidative challenges. Our computations of molecular mechanisms for the antioxidant activities of {111}- and {100}-faceted Pd nanocrystals, as well as their activity order, agree well with experimental observations. These findings can guide the design of antioxidant-mimicking nanomaterials, which could have therapeutic or preventative potential against oxidative stress related diseases.


Assuntos
Antioxidantes/química , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Paládio , Antioxidantes/farmacologia , Oxirredução , Espécies Reativas de Oxigênio
19.
ACS Nano ; 10(9): 8690-9, 2016 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-27584033

RESUMO

Graphene quantum dots (GQDs), zero-dimensional carbon materials displaying excellent luminescence properties, show great promise for medical applications such as imaging, drug delivery, biosensors, and novel therapeutics. A deeper understanding of how the properties of GQDs interact with biological systems is essential for these applications. Our work demonstrates that GQDs can efficiently scavenge a number of free radicals and thereby protect cells against oxidative damage. However, upon exposure to blue light, GQDs exhibit significant phototoxicity through increasing intracellular reactive oxygen species (ROS) levels and reducing cell viability, attributable to the generation of free radicals under light excitation. We confirm that light-induced formation of ROS originates from the electron-hole pair and, more importantly, reveal that singlet oxygen is generated by photoexcited GQDs via both energy-transfer and electron-transfer pathways. Moreover, upon light excitation, GQDs accelerate the oxidation of non-enzymic anti-oxidants and promote lipid peroxidation, contributing to the phototoxicity of GQDs. Our results reveal that GQDs can display both anti- and pro-oxidant activities, depending upon light exposure, which will be useful in guiding the safe application and development of potential anticancer/antibacterial applications for GQDs.

20.
Int J Nanomedicine ; 11: 4373-80, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27621628

RESUMO

Self-assembled nanoparticles of the natural polymer, silk fibroin (SF), are a very promising candidate in drug delivery due to their biocompatible and biodegradable properties. In this study, SF nanoparticles loaded with 5-fluorouracil (5-FU) and curcumin with size 217±0.4 nm and with a loading efficacy of 45% and 15% for 5-FU and curcumin, respectively, were prepared. The in vitro release effect of 5-FU and curcumin from nanoparticles was evaluated as ~100% and ~5%, respectively. It has been revealed that the application of such a nanodrug can increase the level of reactive oxygen species, which in turn induces apoptosis of cancer cells in vitro. Animal studies have shown that tumors could be noticeably reduced after being injected with the drug-entrapped nanoparticles. More apoptotic cells were found after 7 days of treatment with SF nanoparticles by a hematoxylin-eosin staining assay. These results demonstrate the future potential of nanoparticle-loaded binary drugs in the treatment of breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Fibroínas/química , Nanopartículas/administração & dosagem , Seda/química , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Curcumina/administração & dosagem , Feminino , Citometria de Fluxo , Fluoruracila/administração & dosagem , Humanos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Polímeros/química , Ensaios Antitumorais Modelo de Xenoenxerto
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