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1.
Aquat Toxicol ; 233: 105790, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33662879

RESUMO

The potential exposure of titanate nanotubes (TNTs) to wildlife and humans may occur as a result of increased use and application as functional nanomaterials. However, there is a dearth of knowledge regarding the pathways of uptake and excretion of TNTs and their toxicity in cells. In this study, three strains of the Tetrahymena genus of free-living ciliates, including a wild type strain (SB210) and two mutant strains (SB255: mucocyst-deficient; NP1: temperature-sensitive "mouthless''), were used to study the pathways of uptake and excretion and evaluate the cytotoxicity of TNTs. The three Tetrahymena strains were separately exposed to 0, 0.01, 0.1, 1 or 10 mg/L of TNTs, and cells were collected at different time points for quantification of intracellular TNTs (e.g., 5, 10, 20, 40, 60, 90 and 120 min) and evaluation of cytotoxicity (12 and 24 h). TNT contents in NP1 and SB255 were greater or comparable to the contents in SB210 while exposure to 10 mg/L TNTs in 120 min. Furthermore, exposure to 10 mg/L TNTs for 24 h caused greater decreases in cell density of NP1 (38.2 %) and SB255 (36.8 %) compared with SB210 (26.5 %) and upregulated the expression of caspase 15 in SB210. Taken together, our results suggested that TNT uptake by pinocytosis and excretion by exocytosis in Tetrahymena, and the exposure could cause cytotoxicity which can offer novel insights into the accumulation kinetics of nanotubes and even nanomaterials in single cell.


Assuntos
Nanotubos/toxicidade , Organismos Geneticamente Modificados/efeitos dos fármacos , Tetrahymena/efeitos dos fármacos , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Transporte Biológico , Corantes , Relação Dose-Resposta a Droga , Exocitose/efeitos dos fármacos , Humanos , Cinética , Organismos Geneticamente Modificados/metabolismo , Pinocitose/efeitos dos fármacos , Tetrahymena/genética , Tetrahymena/metabolismo , Titânio/metabolismo , Poluentes Químicos da Água/metabolismo
2.
Life Sci ; 257: 118108, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32682920

RESUMO

AIM: Preparation of pegylated gold nanorods (PEG-AuNRs) that are capable of converting near infrared (NIR) light into heat. Evaluation of cancer therapeutic efficacy and long-term toxicity of the proposed photothermal therapy in comparison with other conventional modalities. MATERIALS AND METHODS: Prepared PEG-AuNRs were characterized by measuring their absorption spectra, zeta potential, and transmission electron microscope (TEM). Cancer therapeutic efficacy was assessed by monitoring tumor growth, measuring DNA damage and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in addition to examining tumor histopathology. Further analysis concerning the toxicity of all the proposed treatment modalities was also assessed by evaluating the cytotoxicity and genotoxicity in liver and kidney tissues. KEY FINDINGS: The results demonstrated that both photothermal therapy (PEG-AuNRs + NIR laser) and chemotherapy (cisplatin) have higher efficacy in diminishing Ehrlich tumor growth with significance DNA damage over the other treatment modalities. Concerning the biosafety issue, mice treated photothermally exhibited lower MDA level and higher SOD activity in liver and kidney tissues compared with other treated groups. DNA damage represented by tail moment and olive moment of kidney tissues exhibited lower values for photothermal treated group and higher values for cisplatin treated group. SIGNIFICANCE: Photothermal therapy (PEG-AuNRs + NIR laser) potentiates higher efficacy in treating Ehrlich tumor with minimum toxicity in comparison with other conventional treatment modalities.


Assuntos
Carcinoma de Ehrlich/terapia , Ouro/administração & dosagem , Nanotubos/toxicidade , Fototerapia/métodos , Animais , Carcinoma de Ehrlich/patologia , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Feminino , Ouro/uso terapêutico , Ouro/toxicidade , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Nanotubos/ultraestrutura , Transplante de Neoplasias , Estresse Oxidativo , Superóxido Dismutase/metabolismo
3.
Nanotoxicology ; 14(8): 1017-1038, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32574508

RESUMO

Nanomaterials (NMs) with tubular structures, such as halloysite nanotubes (HNTs), have potential applications in biomedicine. Although the biocompatibility of HNTs has been investigated before, the toxicity of HNTs to blood vessels is rarely systemically evaluated. Herein, we compared the toxicity of HNTs and multi-walled carbon nanotubes (MWCNTs) to human umbilical vein endothelial cells (HUVECs) in vitro and blood vessels of mice in vivo. HUVECs internalized HNTs and MWCNTs, but the uptake of HNTs was not obviously changed by clathrin inhibitor. Exposure to NMs decreased cellular viability, activated apoptotic proteins and up-regulated adhesion molecules, including soluble vascular cell adhesion molecule 1 (sVCAM-1) and VCAM-1. As the mechanisms, NMs decreased NO levels, eNOS mRNA and eNOS/p-eNOS proteins. Meanwhile, NMs promoted intracellular ROS and autophagy dysfunction, shown as decreased protein levels of LC3, beclin-1 and ATG5. The eNOS regulator Kruppel-like factor 4 (KLF4) was inhibited, but another eNOS regulator KLF4 was surprisingly up-regulated. Under in vivo conditions, ICR mice intravenously injected with NMs (50 µg/mouse, once a day for 5 days) showed an increased percentage of neutrophils, monocytes and basophils. Meanwhile, autophagy dysfunction, eNOS uncoupling, activation of apoptotic proteins and alteration of KLF proteins were also observed in mouse aortas. All of the toxic effects were more pronounced for MWCNTs in comparison with HNTs based on the same mass concentrations. Our results may provide novel insights about the toxicity of NMs with tubular structures to blood vessels. Considering the toxicological data reported here, HNTs are probably safer nanocarriers compared with MWCNTs.


Assuntos
Aorta/efeitos dos fármacos , Argila/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Nanotubos/toxicidade , Animais , Aorta/metabolismo , Aorta/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Contagem de Células Sanguíneas , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Nanotubos/química , Nanotubos de Carbono/química , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
4.
J Photochem Photobiol B ; 204: 111784, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954266

RESUMO

Present work compares the green synthesis of iron oxide nanorodes (NRs) using Withania coagulans and reduction precipitation based chemical method. UV/Vis confirmed the sharp peak of Iron oxide NRs synthesized by biologically and chemically on 294 and 278 nm respectively. XRD and SEM showed highly crystalline nature of NRs with average size 16 ± 2 nm using Withania extract and less crystalline with amorphous Nanostructure of 18 ± 2 nm by chemical method. FTIR analysis revealed the involvement of active bioreducing and stabilizing biomolecules in Withania coagulans extract for synthesis of NRs. Moreover, EDX analysis indicates 34.91% of Iron oxide formation in biological synthesis whereas 25.8% of iron oxide synthesis in chemical method. The degradation of safranin dye in the presence of Withania coagulans based NRs showed 30% more effectively than chemically synthesized Nanorods which were verified by the gradual decrease in the peak intensity at 553 nm and 550 nm respectively under solar irradiation. Furthermore, Withania coagulans based NRs showed effective Antibacterial activity against S.aureus and P. aeuroginosa as compared to NRs by chemical method. Finally, we conclude that green synthesized NRs are more effective and functionally more efficient than chemically prepared NRs. Therefore, our work will help the researchers to boost the synthesis of nanoparticles via biological at commercial level.


Assuntos
Antibacterianos/química , Compostos Férricos/química , Nanotubos/química , Extratos Vegetais/química , Withania/química , Antibacterianos/farmacologia , Catálise , Química Verde , Nanotubos/toxicidade , Fenazinas/química , Fotólise/efeitos dos fármacos , Fotólise/efeitos da radiação , Folhas de Planta/química , Folhas de Planta/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Luz Solar , Withania/metabolismo
5.
Environ Toxicol Pharmacol ; 73: 103266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707308

RESUMO

The toxicological potential of halloysite nanotubes (HNTs) and variants after functional alterations to surface area are not clear. We assessed the toxicological response to HNTs (NaturalNano (NN)) before and after surface etching (NN-etched). Potential cytotoxicity of the two HNTs was screened in vitro in MutaTMMouse lung epithelial cells. Lung inflammation, acute phase response and genotoxicity were assessed 1, 3, and 28 days after a single intratracheal instillation of adult female C57BL/6 J BomTac mice. The doses were 6, 18 or 54 µg of HNTs, compared to vehicle controls and the Carbon black NP (Printex 90) of 162 µg/mouse. The cellular composition of bronchoalveolar lavage (BAL) fluid was determined as a measure of lung inflammation. The pulmonary and hepatic acute phase responses were assessed by Serumamyloida mRNA levels in lung and liver tissue by real-time quantitative PCR. Pulmonary and systemic genotoxicity were analyzed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The etched HNT (NN-etched) had 4-5 times larger BET surface area than the unmodified HNT (NN). Instillation of NN-etched at the highest dose induced influx of neutrophils into the lungs at all time points and increased Saa3 mRNA levels in lung tissue on day 1 and 3 after exposure. No genotoxicity was observed at any time point. In conclusion, functionalization by etching increased BET surface area of the studied NN and enhanced pulmonary inflammatory toxicity in mice.


Assuntos
Reação de Fase Aguda , Argila , Pulmão/efeitos dos fármacos , Nanotubos/toxicidade , Animais , Líquido da Lavagem Broncoalveolar , Ensaio Cometa , Camundongos , Camundongos Endogâmicos C57BL , Nanotubos/química , Pneumonia
6.
Toxicol In Vitro ; 62: 104689, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629902

RESUMO

Titanate nanotubes (TiNTs) have been considered as biocompatible nanomaterials (NMs) for biomedical uses. Hereby, we compared the toxicity of TiNTs and TiO2 nanoparticles (NPs) to human umbilical vein endothelial cells (HUVECs). Our results showed that TiNTs were less effectively internalized into HUVECs compared with TiO2 NPs, but none of the NMs induced cytotoxicity or activation of endoplasmic reticulum (ER) stress biomarkers. In addition, intracellular reactive oxygen species (ROS) was only modestly induced by TiNTs and TiO2 NPs. However, both types of NMs significantly promoted the protein levels of vascular cell adhesion molecule-1 (VCAM-1). TiNTs also promoted the release of soluble (sVCAM-1), but THP-1 monocyte adhesion onto HUVECs was only induced by TiO2 NPs. TiNTs decreased the production of NO, associated with a decrease of protein levels of endothelial NO synthase (eNOS). The transcription factors of eNOS, including kruppel-like factor 2 (KLF2) and KLF4, were more effectively down-regulated by TiNTs compared with TiO2 NPs. In conclusion, our results indicated that TiNTs, albeit not cytotoxic, might impair NO signaling pathway in human endothelial cells leading to the activation of endothelial cells.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Nanotubos/toxicidade , Óxido Nítrico/fisiologia , Transdução de Sinais/efeitos dos fármacos , Titânio/toxicidade , Humanos , Fatores de Transcrição Kruppel-Like/biossíntese , Monócitos/efeitos dos fármacos , Nanoestruturas/toxicidade , Óxido Nítrico Sintase Tipo III/biossíntese , Óxido Nítrico Sintase Tipo III/genética , Espécies Reativas de Oxigênio , Molécula 1 de Adesão de Célula Vascular/biossíntese
7.
Environ Pollut ; 258: 113758, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31881510

RESUMO

Natural halloysite nanotubes (HNTs) with a hollow lumen are already applied in numerous fields and enter the environment in increasing quantities, which may have effects on animal and human health. However their in vivo toxicity in mammals is still largely unclear. The aim of this study is to assess acute oral toxicity of HNTs in the stomach of mice and recovery. Oral HNTs at low dose (5 mg HNTs/kg BW) for 30 days increased in daily food and water intake and promoted mouse growth with no obvious adverse effect on the stomach. The promotive effect on mouse growth disappeared after cessation of oral administration of the nanotubes. Oral HNTs for 30 days at high dose (50 mg HNTs/kg BW) induced Si and Al accumulation in the stomach, which caused oxidative stress, inflammation and iNOS-mediated damage in the organ. The damage in the stomach led to slight atrophic gastritis and reduced mouse growth. Oral HNTs-induced changes at high dose were not observed after a 30-days recovery period. The findings provided the evidence that oral HNTs-induced acute toxicity in the stomach was reversible. More importantly, this research showed that Al and Si were cleared out of the mice by hepatic excretion and renal excretion, respectively, during the recovery period. The results suggest that HNTs at low concentration in environments have no adverse effect on mice, while there are health risks to mice under severe contamination by HNTs.


Assuntos
Argila , Nanotubos/toxicidade , Óxido Nítrico Sintase Tipo II/metabolismo , Estômago/enzimologia , Administração Oral , Alumínio , Animais , Camundongos , Estresse Oxidativo , Silício , Estômago/efeitos dos fármacos , Testes de Toxicidade Aguda
8.
Langmuir ; 35(47): 15287-15294, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31674789

RESUMO

Effective bone tissue reconstitution improves the treatment success rate of dental implantation and preserves natural teeth during periodontal tissue repair. Hydroxyapatite (HAp) has received much attention in bone remodeling field because its mineralized structure is similar to that of the natural bone tissue. For this reason, it has been used as a carrier for growth factors. Although HAp possesses outstanding biomedical properties, its capacity of loading and releasing bone growth factors and promoting osteogenesis is not well understood. In this study, Ln3+ (Ln = Yb3+, Er3+, Gd3+)-doped HAp (HAp:Ln3+) nanorods were synthesized by one-step hydrothermal method. To improve its biocompatibility and surface properties, bone morphogenetic protein-2 (BMP-2) was loaded onto the surface of HAp:Ln3+ nanorods. The results showed that BMP-2 incorporation promoted bone formation and enhanced the expression of early bone-related gene and protein (RunX2, SP7, OPN). In addition, Yb3+- and Er3+-doped HAp nanorods were examined by upconversion luminescence with 980 nm near-infrared laser irradiation to monitor the delivery position of BMP-2 protein. Furthermore, due to the positive magnetism correlated with the concentration of Gd3+, HAp:Ln3+ with enhanced contrast brightening can be deemed as T1 MIR contrast agents. These findings indicate that HAp doped with rare-earth ions and loaded with BMP-2 has the potential to promote bone tissue repair and execute dual-mode imaging.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Diferenciação Celular/efeitos dos fármacos , Durapatita/química , Nanotubos/química , Animais , Proteína Morfogenética Óssea 2/química , Bovinos , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Durapatita/efeitos da radiação , Durapatita/toxicidade , Feminino , Expressão Gênica/efeitos dos fármacos , Raios Infravermelhos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/efeitos da radiação , Elementos da Série dos Lantanídeos/toxicidade , Camundongos , Microscopia de Fluorescência/métodos , Nanotubos/efeitos da radiação , Nanotubos/toxicidade , Osteogênese/efeitos dos fármacos , Osteopontina/genética , Osteopontina/metabolismo , Soroalbumina Bovina/química , Fator de Transcrição Sp7/genética , Fator de Transcrição Sp7/metabolismo
9.
Expert Opin Drug Deliv ; 16(11): 1169-1182, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31486344

RESUMO

Introduction: Halloysite clay nanotubes (HNTs) are a naturally abundant and biocompatible aluminosilicate material with a structure able to encapsulate 10-20% of drugs. These features are attractive toward the clinical application in controlled drug delivery, tissue engineering and regenerative medicine. Areas covered: We describe the application of HNTs as a viable method for clinical purposes, particularly developing formulations for prophylaxis, diagnosis and therapeutics, having a special attention to these nanotubes bio-safety. HNTs may be used for pharmaceuticals, biopharmaceuticals, wound healing, bone regeneration, dental repair, hair surface engineering and biomimetic applications. Expert opinion: HNTs are a versatile, safe and biocompatible nanomaterial used for drug encapsulation for numerous clinical applications. The studies here reviewed confirm the HNTs biocompatibility, describing their low toxicity. Further developments will be made regarding the long-term efficacy of halloysite-based treatments in humans, concentrating mostly on topical applications.


Assuntos
Argila , Sistemas de Liberação de Medicamentos , Nanotubos , Animais , Argila/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Nanotubos/química , Nanotubos/toxicidade
10.
Toxicol Appl Pharmacol ; 382: 114758, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521728

RESUMO

Gold (Au) nanomaterials (NMs), particularly those with PEG surface functionalization, are generally considered to be biocompatible for biomedical applications due to relatively low cytotoxicity. Herein, we investigated the toxicity of PEGylated Au nanorods (NRs) to human umbilical vein endothelial cells (HUVECs), a commonly used in vitro model for human endothelium. We found a previously unknown effect that up to 10 µg/mL Au NRs, albeit not cytotoxic, decreased the mRNA and protein levels of kruppel-like factor 2 (KLF2), a transcription factor with well-documented vasoprotective effects. The results from PCR array showed that a number of genes associated with risk of cardiovascular diseases were altered by Au NRs, and several genes are downstream genes of KLF2 according to ingenuity pathway analysis (IPA). These effects could be observed with or without the presence of inflammatory stimuli lipopolysaccharide (LPS), which suggests a pre-existing inflammatory state is not required for Au NRs to alter KLF2 signaling pathway. We further identified that Au NRs significantly decreased eNOS mRNA/p-eNOS proteins as well as increased MCP-1 mRNA/sMCP-1 release, which are targets of KLF2. Combined, our data revealed a novel pathway that PEGylated Au NPs at non-cytotoxic concentrations might alter KLF leading to the increase of risk of cardiovascular diseases in human endothelial cells. Given the importance of KLF in vascular homeostasis, our data indicate that it is necessary to evaluate the influence of engineered NPs to KLF signaling pathways, especially for NPs with biomedical uses.


Assuntos
Ouro/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Nanotubos/toxicidade , Polietilenoglicóis/toxicidade , Transdução de Sinais/efeitos dos fármacos , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Transdução de Sinais/fisiologia , Transcriptoma/efeitos dos fármacos , Transcriptoma/fisiologia
11.
Mol Pharm ; 16(10): 4149-4164, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31398052

RESUMO

Gold nanorods (GNRs) have gained pronounced recognition in the diagnosis and treatment of cancers driven by their distinctive properties. Herein, a gold-based nanosystem was prepared by utilizing a phospholipid moiety linked to thiolated polyethylene glycol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG-SH, as a surface decorating agent. The synthesized phospholipid-PEG-GNRs displayed good colloidal stability upon exposure to the tissue culture medium. Cytotoxicity of phospholipid-PEG-GNRs was investigated toward MCF-7 and T47D breast cancer cells using sulforhodamine B test. The results revealed that phospholipid-PEG-GNRs demonstrated  high cytotoxicity to MCF-7 cells compared to T47D cells, and minimal cytotoxicity to human dermal fibroblasts. The cellular uptake studies performed by imaging and quantitative analysis demonstrated  massive internalization of phospholipid-coated GNRs into  MCF-7 cells in comparison to T47D cells. The cellular death modality of cancer cells after treatment with phospholipid-PEG-GNRs was evaluated using mitochondrial membrane potential assay (JC-1 dye), gene expression analysis, and flow cytometry study. The overall results suggest that phospholipid-modified GNRs enhanced mainly the cellular apoptotic events in MCF-7 cells in addition to necrosis, whereas cellular necrosis and suppression of cellular invasion contributed to the cellular death modality in the T47D cell line upon treatment with phospholipid-PEG-GNRs. The phospholipid-coated GNRs interact in a different manner with breast cancer cell lines and could be considered for breast cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ouro/química , Nanotubos/toxicidade , Fosfolipídeos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanotubos/química , Polietilenoglicóis/química , Células Tumorais Cultivadas
12.
J Hazard Mater ; 377: 237-248, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31170572

RESUMO

The increasing application of nanomaterials drives the unintentional release of nanoparticles (NPs) into the ocean, which may pose a potential threat to marine organisms. It has been demonstrated that exposure to NPs could chanllenge the immune responses of marine species. However, the affecting mechanism behind remains poorly understood. In this study, the immunotoxic impacts and the mechanisms underpinning the effects of four major NPs, including nZnO, nFe2O3, nCuO, and carbon nanotube (MWCNT), were investigated in blood clam, Tegillarca granosa. The results showed that exposure to tested NPs resulted in reduced total counts, altered cell composition, and constrained phagocytic activities of haemocytes. The intracellular contents of reactive oxygen species (ROS) and the degree of DNA damage of haemocytes were significantly induced, whereas the haemocyte viability was suppressed. Furthermore, NP exposures led to significant increases in the in vivo contents of neurotransmitters. Down-regulations of the immune- and neurotransmitter-related genes were detected as well. Our data suggest that NP exposures hampered the immune responses of blood clams most likely through (1) inducing ROS, causing DNA damage, and reducing cell viability of haemocytes, (2) altering the in vivo contents of neurotransmitters, and (3) affecting the expression of immune- and neurotransmitter-related genes.


Assuntos
Arcidae/imunologia , Bivalves/imunologia , Imunotoxinas/toxicidade , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Arcidae/efeitos dos fármacos , Bivalves/efeitos dos fármacos , Contagem de Células , Ensaio Cometa , Dano ao DNA , Regulação da Expressão Gênica/efeitos dos fármacos , Hemócitos/efeitos dos fármacos , Hemócitos/imunologia , Nanopartículas Metálicas/toxicidade , Nanotubos/toxicidade , Neurotransmissores/metabolismo , Fagocitose/efeitos dos fármacos , Espécies Reativas de Oxigênio
13.
Sci Total Environ ; 682: 70-79, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31108270

RESUMO

Gold nanorods have shown to pose adverse effects to biota. Whether these effects may be potentiated through prolonged exposure has been rarely studied. Therefore, this work aimed at evaluating the effects of long-term exposure to sublethal levels of cetyltrimethylammonium bromide (CTAB) coated gold nanorods (Au-NR) on two freshwater microalgae: Chlorella vulgaris and Raphidocelis subcapitata. These algae were exposed to several concentrations of Au-NR for 72 h and, afterwards, to the corresponding EC5,72h, for growth, during 16 days. The sensitivity of the two algae to Au-NR was assessed at days 0, 4, 8, 12 and 16 (D0, D4, D8, D12 and D16, respectively) after a 72-h exposure to several concentrations of Au-NR. At the end of the assays, effects on yield and population growth rate were evaluated. Raphidocelis subcapitata was slightly more sensitive to Au-NR than C. vulgaris: EC50,72h,D0 for yield were 48.1 (35.3-60.9) and 70.5 (52.4-88.6) µg/L Au-NR, respectively while for population growth rate were above the highest tested concentrations (53 and 90 µg/L, respectively). For R. subcapitata the long-term exposure to Au-NR increased its sensitivity to this type of nanostructures. For C. vulgaris, a decrease on the effects caused by Au-NR occurred over time, with no significant effects being observed for yield or population growth rate at D12 and D16. The capping agent CTAB caused reductions in yield above 30% (D0) for both algae at the concentration matching the one at the highest Au-NR tested concentration. When exposed to CTAB, the highest inhibition values were 69% (D4) and 21.3% (D8) for R. subcapitata, and 64% (D12) and 21% (D16) to C. vulgaris, for yield and population growth rate, respectively. These results suggested long-term exposures should be included in ecological risk assessments since short-term standard toxicity may either under- or overestimate the risk posed by Au-NR.


Assuntos
Clorofíceas/efeitos dos fármacos , Coloide de Ouro/toxicidade , Microalgas/efeitos dos fármacos , Nanotubos/toxicidade , Poluentes Químicos da Água/toxicidade , Chlorella vulgaris/efeitos dos fármacos , Água Doce , Fatores de Tempo
14.
ACS Appl Mater Interfaces ; 11(17): 15251-15261, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964253

RESUMO

Macrophage-mediated delivery of drugs or nanoparticles has great potential in cancer treatment because it can avoid interception by the immune system and cross the blood-vessel barriers to reach the hypoxic regions of tumors. However, macrophage-based delivery system still faces some great challenges such as low theranostics agent loading capacity and hypoxic regions tendency in vivo. Herein, small gold nanorods (AuNRs) were used as the model theranostics agent to design a macrophage-mediated delivery system with high loading quantity for tumor hypoxia photoacoustic (PA) imaging and enhanced photothermal therapy (PTT). AuNRs modified with various thiolated poly(ethylene glycol)s (HS-PEG) via ligand exchange were investigated for toxicity and cell uptake by macrophages. The tumor hypoxic regions tendency of macrophage-loaded Anionic-AuNRs (Anionic-AuNRs@RAW) were verified by in vivo PA imaging and tumor sections. In vivo systemic PTT demonstrated enhanced tumor inhibition of anionic-AuNRs@RAW. This macrophage-mediated delivery system with high loading capacity could be used to enhance the effectiveness of cancer treatment.


Assuntos
Ouro/química , Nanotubos/química , Técnicas Fotoacústicas/métodos , Hipóxia Tumoral , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Hipertermia Induzida , Lasers , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanotubos/toxicidade , Neoplasias/patologia , Neoplasias/terapia , Fototerapia , Polietilenoglicóis/química , Células RAW 264.7 , Compostos de Sulfidrila/química
15.
Chemosphere ; 224: 237-246, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30822730

RESUMO

Among nanomaterials, zinc oxide (ZnO) is notable for its excellent biocidal properties. In particular, it can be incorporated in mortars to prevent biofouling. However, the morphology of these nanomaterials (NMs) and their impact on the action against biofouling are still unknown. This study aimed to assess how the morphology and surface modification can affect the ecotoxicology of ZnO NMs. The morphologies evaluated were nanoparticles (NPs) and nanorods (NRs), and the ZnO NMs were tested pure and with surface modification through amine functionalization (@AF). The toxic effects of these NMs were evaluated by acute and chronic ecotoxicity tests with the well-established model microcrustacean Daphnia magna. The ZnO NMs were characterized by transmission electron microscopy, X-ray diffraction and infrared spectroscopy. The EC5048h to D. magna indicated higher acute toxicity of ZnO@AF NRs compared to all tested NMs. Regarding the chronic test with D. magna, high toxic effects on reproduction and longevity were observed with ZnO@AF NRs and effects on growth were observed with ZnO NRs. In general, all tested ZnO NMs presented high toxicity when compared to the positive control, and the NRs presented higher toxicity than NPs in all tested parameters, regardless of the form tested (pure or with surface modification). Additionally, the pathways of ecotoxicity of the tested ZnO NMs was found to be related to combined factors of Zn ion release, effective diameter of particles and NM internalization in the organism.


Assuntos
Daphnia/efeitos dos fármacos , Ecotoxicologia/métodos , Nanoestruturas/toxicidade , Óxido de Zinco/toxicidade , Animais , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Nanoestruturas/ultraestrutura , Nanotubos/toxicidade , Nanotubos/ultraestrutura , Propriedades de Superfície , Testes de Toxicidade , Óxido de Zinco/química
16.
Nanotoxicology ; 13(3): 354-368, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30704318

RESUMO

Nanomaterials are widely used in an ever-increasing number of consumer and industrial products. It is therefore essential that the toxic effects of nanomaterials are understood in order to improve product safety. Here we evaluate the toxicity of inhaled halloysite nanotubes (HNTs) by applying a purpose designed inhalation exposure system and succeed in suppressing HNTs toxicity using trehalose. By assessing apoptosis, oxidative stress, inflammatory response, and autophagy, it is found that HNTs can cause sub-chronic toxicity in mice. Further investigations indicate that HNTs induce autophagy blockade that results in the accumulation of sequestosome-1 (p62), which is responsible for the excessive apoptosis, inflammatory response and oxidative stress. We found that p62 can be eliminated by trehalose and the application of trehalose in vitro and in vivo successfully inhibits toxicity by accelerating the clearance of p62. Trehalose shows great potential for reducing nanoparticle toxicity.


Assuntos
Autofagia/efeitos dos fármacos , Argila/química , Nanotubos/toxicidade , Proteína Sequestossoma-1/metabolismo , Trealose/farmacologia , Animais , Apoptose/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Relação Dose-Resposta a Droga , Exposição por Inalação/efeitos adversos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Nanotubos/química , Estresse Oxidativo/efeitos dos fármacos
17.
Nanoscale ; 11(13): 5920-5931, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30693919

RESUMO

Inflammatory reactions and the functionality of endothelial cells (ECs) on the surfaces of coronary stents are critical in the prevention of in-stent restenosis and subsequent neoatherosclerosis. However, the interactions between immune cells and ECs on modified coronary stent surfaces have long been underestimated. In the present study, silicon (Si)-doped titania nanotube arrays (TNA-Sis) were obtained via the facile anodization of magnetron-sputtered Ti-Si coatings. The synergetic effects of titania nanotube arrays (TNAs) and chemical cues (Si) on the functionality of macrophages (MΦs)/ECs and their cross-talk were investigated. The results indicated that TNA-Sis specimens, in comparison with TNAs alone, not only promoted the initial vitality of ECs, enhanced the expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO), and activated multiple cell signaling pathways (vWF, PECAM, eNOS), but also induced a favorable immune response through the polarization of MΦs to a pro-healing M2 phenotype via the activation of cell autophagy, resulting in the downregulation of inflammatory reactions. This beneficial immune response further facilitated cross-talk between ECs and MΦs, resulting in profoundly increased functionality of ECs on TNA-Sis surfaces. This study demonstrated that using TNA-Sis surface coatings for coronary stents may be a promising strategy to prevent in-stent restenosis.


Assuntos
Comunicação Celular/fisiologia , Nanotubos/química , Silício/química , Titânio/química , Autofagia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Nanotubos/toxicidade , Óxido Nítrico/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Nanoscale ; 11(6): 2655-2667, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30601530

RESUMO

To date, photothermal sensitizers include organic and inorganic nanomaterials for biomedical applications. However, the impediments of low biodegradability and potential toxicity hinder their further applications in clinics. Liquid metal nanospheres show superior photothermal effects under near-infrared laser irradiation, in addition, a transformation in shape can be triggered, which also promotes biodegradability that helps to avoid potential systemic toxicity. Here, we fabricated tunable liquid metal nanoparticles having sphere-shaped to rod-shaped characteristics, resulting in good biocompatibility, favorable photothermal conversion efficiency, and targeting capability to tumors. The synthesis strategy is easy to achieve through one-step sonication. We systematically evaluated the photothermal properties of these liquid metal nanoparticles as well as their destructive effects on tumors in a quantitative way both in vitro and in vivo under laser exposure. Results have shown for the first time in mice that gallium nanorods, regulated and controlled through the production of GaO(OH), displayed outstanding photothermal conversion efficiency and exhibited distinct temperature elevation compared to gallium nanospheres and gallium-indium alloy nanorods. These shape transformable and biocompatible gallium nanorods establish the basis for the future laser ablation of tumors to achieve enhanced therapeutic outcomes. This shape tunability of a smart nano-liquid metal directly contributes to enhanced photothermal therapy in mice and opens new opportunities for potential applications with tumor therapy and imaging.


Assuntos
Técnicas de Ablação/métodos , Gálio/química , Nanopartículas Metálicas/química , Nanotubos/química , Fototerapia/métodos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Gálio/farmacologia , Gálio/toxicidade , Humanos , Receptores de Hialuronatos , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Nus , Nanotubos/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Toxicology ; 413: 24-32, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30528861

RESUMO

Gold nanorods (AuNRs) have been studied extensively in biomedicine due to their biocompatibility and their unique properties. Some studies reported that AuNRs selectively accumulate on cancer cell mitochondria causing its death. However, the immediate effects of this accumulation needed further investigations. In this context, we evaluated the effect of AuNRs on the mitochondrial integrity of isolated rat liver mitochondria. We verified that AuNRs decreased the mitochondrial respiratory ratio by decreasing the phosphorylation and maximal states. Additionally, AuNRs caused a decrease in the production of mitochondrial ROS and a delay in mitochondrial swelling. Moreover, even with cyclosporine A treatment, AuNRs disrupted the mitochondrial potential. With the highest concentration of AuNRs studied, disorganized mitochondrial crests and intermembrane separation were observed in TEM images. These results indicate that AuNRs can interact with mitochondria, disrupting the electron transport chain. This study provides new evidence of the immediate effects of AuNRs on mitochondrial bioenergetics.


Assuntos
Ouro/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Nanotubos/toxicidade , Consumo de Oxigênio/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Ouro/metabolismo , Masculino , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Consumo de Oxigênio/fisiologia , Ratos , Ratos Wistar
20.
J Appl Toxicol ; 39(2): 231-240, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30159912

RESUMO

Understanding the possible role of physicochemical properties in determining the toxicity of ZnO nanomaterials (NMs) is crucial for the safe use of ZnO-based materials. In this study, we synthesized four types of ZnO NMs, and characterized them as ZnO nanorods (NRs; length 400-500 nm, diameter 150-200 nm), ZnO Mini-NRs (length 50-100 nm, diameter 15-20 nm), amorphous ZnO microspheres (a-ZnO MS) and crystalline ZnO MS (c-ZnO MS; the a/c-ZnO MS are nanoflowers with an extensive growth of sheet-like structures). ZnO NMs and ZnO Mini-NRs were significantly more cytotoxic than a/c-ZnO MS, and this trend was similar in both HepG2 cells and human umbilical vein endothelial cells. Intracellular reactive oxygen species was only modestly induced by c-ZnO MS, whereas intracellular Zn ions were dose-dependently increased in HepG2 cells by the exposure of all types of ZnO NMs. The expression of endoplasmic reticulum stress marker DDIT3 was induced following an order of ZnO NRs > a-ZnO MS > c-ZnO MS > ZnO Mini-NRs, and the apoptosis gene CASP12 was induced following an order of a-ZnO MS > ZnO NRs > c-ZnO MS > ZnO Mini-NRs. Combined, these results suggested that ZnO NM-induced cytotoxicity and expression of endoplasmic reticulum stress-apoptosis genes could be influenced by the size and shape of ZnO NMs.


Assuntos
Hepatócitos/efeitos dos fármacos , Nanotubos/química , Nanotubos/toxicidade , Óxido de Zinco/química , Óxido de Zinco/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Hepatócitos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Microesferas , Tamanho da Partícula , Propriedades de Superfície
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