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1.
J Environ Sci (China) ; 85: 94-106, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471036

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) are subjected to various transformation processes (chemical, physical and biological processes) in the environment, potentially affecting their bioavailability and toxic properties. However, the size variation of TiO2 NPs during aging process and subsequent effects in mammalian cells are largely unknown. The aim of this study was to illustrate the adverse effects of TiO2 NPs in different sizes (5, 15 and <100 nm) during aging process on human-hamster hybrid (AL) cells. There was an aging-time dependent enhancement of average hydrodynamic size in TiO2 NPs stock suspensions. The cytotoxicity of fresh TiO2 NPs increased in a size-dependent manner; in contrast, their genotoxicity decreased with the increasing sizes of NPs. No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO2 NPs. Both Fresh and aged TiO2 NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner. Using mitochondrial-DNA deficient (ρ0) AL cells, we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO2 NPs during the aging process. Taken together, our data indicated that TiO2 NPs could significantly induced the cytotoxicity and genotoxicity in an aging time-independent and size-dependent manner, which were triggered by mitochondrial dysfunction. Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO2 NPs disposal before entering the environment.


Assuntos
Nanopartículas/toxicidade , Titânio/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Dano ao DNA , Humanos , Testes de Toxicidade
2.
Chem Biol Interact ; 311: 108774, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369748

RESUMO

Silica nanoparticles (SiNPs) are one of the popular nanomaterials used in industrial manufacturing, synthesis, engineering, and medicine. Recently, mechanisms underlying toxicity of silica nanoparticles have been reported; however, their uptake mechanisms have still not fully understood. In this study, toxicity of SiNPs was investigated in the nematode Caenohabditis elegans by using microarray and pathway analysis focusing the uptake mechanisms and their impact on toxicity. Physicochemical characterization of SiNPs was performed using dynamic light scattering (DLS) and zeta potential. No mortality was observed after 24 h exposure to SiNPs. However, reproductive ability was significantly reduced at the same concentrations. To ascertain a global mechanism of toxicity, microarray was conducted on C. elegans exposed to 10 mg/L SiNPs (20% reduction in reproductive ability). Microarray results indicated that genes involved in reproduction, such as msp (Major Sperm Protein) genes, were significantly downregulated in C. elegans exposed to SiNPs. Pathway analyses on differentially expressed genes (DEGs) revealed that endocytic pathway as a major pathway involved in the uptake of SiNPs. Involvement of endocytic pathway in the uptake of SiNPs was assessed using specific inhibitors (methyl-ß-cyclodextrin, chlorpromazine, and LY294002 for caveolin-, clathrin-, and pinocytosis-mediated endocytosis, respectively). The inhibitor assay indicated that an internalization process facilitated by clathrin-mediated endocytosis is involved in the uptake of SiNPs. Functional analysis using endocytosis defective mutants, (i,e.  cav-1, cup-2, and chc-1) confirmed the role of endocytosis on the reproductive toxicity of SiNPs. Overall results suggest that clathrin-mediated endocytosis pathway is a potential mechanism of uptake of SiNPs in C. elegans that in turn, affects general toxic outcome, such as, decrease in reproductive ability.


Assuntos
Caenorhabditis elegans/metabolismo , Clatrina/metabolismo , Endocitose/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/química , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Redes Reguladoras de Genes/efeitos dos fármacos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia
3.
Int J Nanomedicine ; 14: 5135-5146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371952

RESUMO

Nanoparticles appear to be one of the most promising agents that offer efficacy in angiogenesis-related disease therapy. The objective of this research is to systematically review studies that have probed into the effect of nanoparticles on angiogenesis. Selected inclusion criteria were used to extract articles, references that were cited in the initial search were sought to identify more potential articles, and articles that did not meet the inclusion criteria and duplicates were discarded. The spherical shape was shown to be the most common shape employed to investigate the role of nanoparticles in angiogenesis therapy. The size of nanoparticles appears to play a crucial role for efficacy on angiogenesis, in which 20 nm emerged as the preferred size. Gold nanoparticles exhibit the most promise as an antiangiogenesis agent, and the toxicity was adjustable based on the dosages applied.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Nanopartículas/uso terapêutico , Humanos , Nanopartículas/toxicidade , Neovascularização Patológica/tratamento farmacológico , Tamanho da Partícula
4.
J Agric Food Chem ; 67(33): 9382-9389, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31361959

RESUMO

Early stage exposure of foodborne substances, such as brightening agent titanium dioxide nanoparticles (TiO2 NPs), can cause long-term effects in adulthood. We aimed to explore the potential adverse effect of long-term dietary intake of TiO2 NPs. After feeding for 2-3 months from weaning, TiO2 NPs-exposed mice showed lower body weight and induced intestinal inflammation. However, this phenomenon was not observed in gut microbiota-removed mice. TiO2 NPs exposure rarely affected the diversity of microbial communities, but significantly decreased the abundance of several probiotic taxa including Bifidobacterium and Lactobacillus. Additionally, TiO2 NPs aggravated DSS-induced chronic colitis and immune response in vivo, and reduced the population of CD4+T cells, regulatory T cells, and macrophages in mesenteric lymph nodes. Therefore, dietary TiO2 NPs could interfere with the balance of immune system and dynamic of gut microbiome, which may result in low-grade intestinal inflammation and aggravated immunological response to external stimulus, thus introducing potential health risk.


Assuntos
Intestinos/efeitos dos fármacos , Intestinos/imunologia , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Titânio/metabolismo , Titânio/toxicidade , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Fatores de Tempo
5.
Int J Nanomedicine ; 14: 4573-4587, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296987

RESUMO

Introduction: Engineered nanoparticles (ENPs) are one of the most widely used types of nanomaterials. Recently, ENPs have been shown to cause cellular damage by inducing ROS (reactive oxygen species) both directly and indirectly, leading to the changes in DNA methylation levels, which is an important epigenetic mechanism. In this study, we investigated the effect of ENP-induced ROS on DNA methylation. Materials and methods: Human embryonic kidney and human keratinocyte (HaCaT) cells were exposed to three different types of ENPs: gold nanoparticles, silicon nanoparticles (SiNPs), and chitosan nanoparticles (CSNPs). We then evaluated the cytotoxicity of the ENPs by measuring cell viability, morphology, cell apoptosis, cell proliferation, cell cycle distribution and ROS levels. Global DNA methylation levels was measured using 5-methylcytosine immunocytochemical staining and HPLC analysis. DNA methylation levels of the transposable elements, long interspersed element-1 (LINE-1) and Alu, were also measured using combined bisulfite restriction analysis technique. DNA methylation levels of the TEs LINE-1 and Alu were also measured using combined bisulfite restriction analysis technique. Results: We found that HaCaT cells that were exposed to SiNPs exhibited increased ROS levels, whereas HaCaT cells that were exposed to SiNPs and CSNPs experienced global and Alu hypomethylation, with no change in LINE-1 being observed in either cell line. The demethylation of Alu in HaCaT cells following exposure to SiNPs and CSNPs was prevented when the cells were pretreated with an antioxidant. Conclusion: The global DNA methylation that is observed in cells exposed to ENPs is associated with methylation of the Alu elements. However, the change in DNA methylation levels following ENP exposure is specific to particular ENP and cell types and independent of ROS, being induced indirectly through disruption of the oxidative defense process.


Assuntos
Acetilcisteína/farmacologia , Metilação de DNA/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/toxicidade , Elementos Alu/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/metabolismo , Epigênese Genética , Ouro/metabolismo , Humanos , Queratinócitos/efeitos dos fármacos , Elementos Nucleotídeos Longos e Dispersos/efeitos dos fármacos , Coroa de Proteína , Espécies Reativas de Oxigênio/metabolismo , Silício/química
6.
Sci Total Environ ; 690: 502-510, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31301491

RESUMO

Copper oxide nanoparticles (CuO NPs), as an antimicrobial nanomaterial, have found many applications in agriculture. Ubiquitous and complex root exudates (RE) in the plant root zone motivates the determination of how specific components of RE interact with CuO NPs. This work aims to reveal the role of maize (Zea mays L.)-derived RE and their components on the aggregation and dissolution of CuO NPs in the rhizosphere. We observed that RE significantly inhibited the aggregation of CuO NPs regardless of ionic strength and electrolyte type. In the presence of RE, the CCC of CuO NPs in NaCl shifted from 30 to 125 mM and the value in CaCl2 shifted from 4 to 20 mM. Furthermore, this inhibition was correlated with molecular weight (MW) of RE fractions. Higher MW fraction (>10 kDa) reduced the aggregation most. We also discovered that RE significantly promoted the dissolution of CuO NPs and lower MW fraction (<3 kDa) RE mainly contributed to this process. Additionally, phytotoxicity of CuO NPs in the presence of RE and different fractions of RE was evaluated. The addition of 20 mg/L RE reduced the seedlings growth rate to 1.89% after 7 days exposure to 25 mg/L CuO NPs, which were significantly lower than the control group (4.82%). Notably, Cu accumulation in plant root tissues was significantly enhanced by 20 mg/L RE. This study provides useful insights into the interactions between RE and CuO NPs, which is of significance for the safe use of CuO NPs-based antimicrobial products in agricultural production.


Assuntos
Nanopartículas/química , Exsudatos de Plantas/química , Zea mays/química , Cobre , Nanopartículas/toxicidade , Concentração Osmolar , Exsudatos de Plantas/toxicidade , Raízes de Plantas/química , Rizosfera , Zea mays/toxicidade
7.
Int J Nanomedicine ; 14: 4867-4880, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308663

RESUMO

Background: The demand for an effective vaccine delivery system that drives a suitable immune response is increasing. The oxidized carbon nanosphere (OCN), a negatively charged carbon nanoparticle, has the potential to fulfill this requirement because it can efficiently deliver macromolecules into cells and allows endosomal leakage. However, fundamental insights into how OCNs are taken up by antigen-presenting cells, and the intracellular behavior of delivered molecules is lacking. Furthermore, how immune responses are stimulated by OCN-mediated delivery has not been investigated. Purpose: In this study, the model protein antigen ovalbumin (OVA) was used to investigate the uptake mechanism and intracellular fate of OCN-mediated delivery of protein in macrophages. Moreover, the immune response triggered by OVA delivered by OCNs was characterized. Methods: Bone-marrow-derived macrophages (BMDMs) from mice were used to study antigen uptake and intracellular trafficking. Mice were immunized using OCN-OVA combined with known adjuvants, and the specific immune response was measured. Results: OCNs showed no cytotoxicity against BMDMs. OCN-mediated delivery of OVA into BMDMs was partially temperature independent process. Using specific inhibitors, it was revealed that intracellular delivery of OCN-OVA does not rely on phagocytosis or the clathrin- and lipid raft/caveolae-mediated pathways. Delivered OVA was found to colocalize with compartments containing MHC class I, but not with early endosomes, lysosomes, and autophagosomes. Immunization of OVA using OCNs in combination with the known adjuvant monophosphoryl lipid A specifically enhanced interferon gamma (IFNγ)- and granzyme B-producing cytotoxic T cells (CTLs). Conclusion: OCNs effectively delivered protein antigens into macrophages that localized with compartments containing MHC class I partially by the temperature independent, but not clathrin- and lipid raft/caveolae-mediated pathways. Increased CD8+ T-cell activity was induced by OCN-delivered antigens, suggesting antigen processing toward antigen presentation for CTLs. Taken together, OCNs are a potential protein antigen delivery system that stimulates the cell-mediated immune response.


Assuntos
Antígenos/administração & dosagem , Carbono/química , Sistemas de Liberação de Medicamentos , Imunidade Celular , Nanopartículas/química , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos/imunologia , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Linhagem Celular , Endocitose/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Feminino , Imunidade Celular/efeitos dos fármacos , Cinética , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Nanopartículas/toxicidade , Oxirredução , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
8.
Ecotoxicol Environ Saf ; 182: 109421, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31301592

RESUMO

The environmental contamination of soil by metal oxide nanomaterials is a growing global concern because of their potential toxicity. We investigated the effects of Mg doped ZnO (Mg-nZnO) nanoparticles on a model soil microorganism Bacillus subtilis. Mg-nZnO exhibited only a moderate toxic effect on B. subtilis vegetative cells but was able to prevent biofilm formation and destroy already formed biofilms. Similarly, Mg-nZnO (≤1 mg/mL) was moderately toxic towards Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Salmonella enterica, Saccharomyces cerevisiae and murine macrophages. Engineered Mg-nZnO produced H2O2 and O2•- radicals in solutions of various salt and organic molecule compositions. A quantitative proteomic analysis of B. subtilis membrane proteins showed that Mg-nZnO increased the expression of proteins involved in detoxification of ROS, translation and biofilm formation. Overall, our results suggest that Mg-nZnO released into the environment may hinder the spreading, colonization and biofilm formation by B. subtilis but also induce a mechanism of bacterial adaptation.


Assuntos
Bacillus subtilis/efeitos dos fármacos , Nanopartículas/toxicidade , Poluentes do Solo/toxicidade , Óxido de Zinco/toxicidade , Animais , Biofilmes , Escherichia coli/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Camundongos , Óxidos/metabolismo , Proteômica , Solo , Microbiologia do Solo , Staphylococcus aureus
9.
Chemosphere ; 233: 363-372, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31176899

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) find applications in our day-to-day life because of unique physicochemical properties. Their release into the aquatic environment poses a possible risk to the organisms. However, the continuing exposure of NPs might reduce their bioavailability to marine organisms owing to aggregation and sedimentation in the aqueous systems thus significantly reducing their toxic impact. In this regard, the present study investigates the effect of continuous exposure of TiO2 NPs to marine microalgae Chlorella sp. under UV-A irradiation through "tanks in series" mode of experiments. In a three-cycle experiment, concentration of TiO2 NPs in the first cycle was fixed at 62.6 µM, and the interacted nanoparticles was subsequently exposed to fresh batches of algae in the next two cycles. After the interaction, the NPs underwent severe aggregation (mean hydrodynamic diameter 3000 ±â€¯18.2 nm after cycle I) leading to gravitational settling in the medium and thus decreased bioavailability. The aggregation can be attributed to interactions between the particles themselves (homo-aggregation) further aggravated by the presence of the algal cells (hetero-aggregation). Cellular viability after cycle I was found to be only 24.2 ±â€¯2.5%, and it was enhanced to 96.5 ±â€¯2.8% after the cycle III in the course of continuous exposure. The results were validated with estimation of oxidative stress markers such as intracellular ROS (total ROS, superoxide and hydroxyl radicals) and LPO after each cycle of exposure. The continuing decrease in the EPS across the cycles further confirmed the diminishing toxicity of the NPs.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Chlorella/efeitos dos fármacos , Microalgas/efeitos dos fármacos , Nanopartículas/toxicidade , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Organismos Aquáticos/metabolismo , Disponibilidade Biológica , Chlorella/metabolismo , Exposição Ambiental , Microalgas/metabolismo , Modelos Teóricos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Titânio/química , Titânio/metabolismo , Raios Ultravioleta , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismo
10.
Chemosphere ; 233: 482-492, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31181495

RESUMO

Rise in cyanobacterial blooms and massive discharge of nanoparticles (NPs) in aquatic ecosystems cause zooplankton to be exposed in toxic food and NPs simultaneously, which may impact on zooplankton interactively. Therefore, the present study focused on assessing the combined effects of different ZnO NPs levels (0, 0.10, 0.15, 0.20 mg L-1) and different proportions of toxic Microcystis (0%, 10%, 20%, 30%) in the food on a model zooplankton, Daphnia magna. The results showed that both toxic Microcystis and ZnO NPs significantly delayed the development of D. magna to maturation, but there was no significant interaction between the two factors on the times to maturation except the body length at maturation. Both ZnO NPs and toxic Microcystis also significantly decreased the number of neonates in the first brood, total offspring, and number of broods per female, and there was a significant interaction between ZnO NPs and food composition on the reproductive performance of D. magna. Specifically, presence of toxic Microcystis reduced the gap among the effects of different ZnO NPs concentrations on the reproductive performance of D. magna. When the ZnO NPs concentration was at 0.15 mg L-1, the gap of the reproductive performance among different proportions of toxic Microcystis also tended to be narrow. Similar phenomenon also occurred in mortality. Such results suggested that low concentration of ZnO NPs and toxic Microcystis can mutually attenuate their harmful effects on D. magna, which has significantly implications in appropriately assessing the ecotoxicological effects of emerging pollutants in a complex food conditions.


Assuntos
Daphnia/efeitos dos fármacos , Microcystis/química , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidade , Óxido de Zinco/toxicidade , Animais , Feminino , Cadeia Alimentar , Humanos , Traços de História de Vida , Reprodução/efeitos dos fármacos , Zooplâncton/efeitos dos fármacos , Zooplâncton/crescimento & desenvolvimento
11.
Int J Nanomedicine ; 14: 4229-4245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239677

RESUMO

Purpose: Gene therapies via Noggin small interfering (si)RNA (siNoggin) and bone morphogenetic protein (BMP)-2 plasmid DNA (pBMP-2) may be promising strategies for bone repair/regeneration, but their ideal delivery vectors, efficacy difference, and underlying mechanisms have not been explored, so these issues were probed here. Methods: This study used lipopolysaccharide-amine nanopolymersomes (LNPs), an efficient cytosolic delivery vector developed by the research team, to mediate siNoggin and pBMP-2 to transfect MC3T3-E1 cells, respectively. The cytotoxicity, cell uptake, and gene knockdown efficiency of siNoggin-loaded LNPs (LNPs/siNoggin) were studied, then the osteogenic-differentiation efficacy of MC3T3-E1 cells treated by LNPs/pBMP-2 and LNPs/siNoggin, respectively, were compared by measuring the expression of osteogenesis-related genes and proteins, alkaline phosphatase (ALP) activity, and mineralization of the extracellular matrix at all osteogenic stages. Finally, the possible signaling pathways of the two treatments were explored. Results: LNPs delivered siNoggin into cells efficiently to silence 50% of Noggin expression without obvious cytotoxicity. LNPs/siNoggin and LNPs/pBMP-2 enhanced the osteogenic differentiation of MC3T3 E1 cells, but LNPs/siNoggin was better than LNPs/pBMP-2. BMP/Mothers against decapentaplegic homolog (Smad) and glycogen synthase kinase (GSK)-3ß/ß-catenin signaling pathways appeared to be involved in osteogenic differentiation induced by LNPs/siNoggin, but GSK-3ß/ß-catenin was not stimulated upon LNPs/pBMP-2 treatment. Conclusion: LNPs are safe and efficient delivery vectors for DNA and RNA, which may find wide applications in gene therapy. siNoggin treatment may be a more efficient strategy to enhance osteogenic differentiation than pBMP-2 treatment. LNPs loaded with siNoggin and/or pBMP-2 may provide new opportunities for the repair and regeneration of bone.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Proteínas de Transporte/metabolismo , Diferenciação Celular , Lipopolissacarídeos/farmacologia , Nanopartículas/química , Osteogênese , Polímeros/química , RNA Interferente Pequeno/administração & dosagem , Fosfatase Alcalina/metabolismo , Aminas/química , Animais , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Matriz Extracelular/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos , Minerais/química , Nanopartículas/toxicidade , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Plasmídeos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transfecção , beta Catenina/metabolismo
12.
Int J Nanomedicine ; 14: 3491-3502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190806

RESUMO

Background: Studies have showed that nanoparticles have a certain anti-cancer activity and can inhibit many kinds of cancer cells. ß-tricalcium phosphate nanoparticles (nano-ß-TCP) displays better biodegradation, but the application and mechanism of nano-ß-TCP in anti-cancer activity are still not clear. Purpose: The objective of this study was to synthesize nano-ß-TCP and investigate its inhibitory properties and mechanism on hepatocellular carcinoma (HepG2) cells in vitro and in vivo. Methods: Nano-ß-TCP was synthesized using ethanol-water system and characterized. The effects of nano-ß-TCP on cell viability, cell uptake, intracellular oxidative stress (ROS), cell cycle and apoptosis were also investigated with HepG2 cells and human hepatocyte cells (L-02). Intratumoral injection of nano-ß-TCP was performed on the xenograft liver cancer model to explore the inhibitory effect and mechanism of nano-ß-TCP on liver tumors. Results: In vitro results revealed that nano-ß-TCP caused reduced cell viability of HepG2 cells in a time-and dose-dependent manner. Nano-ß-TCP was internalized through endocytosis and degraded in cells, resulting in obvious increase of the intracellular Ca2+ and PO4 3- ions. Nano-ß-TCP induced cancer cells to produce ROS and induced apoptosis of tumor cells by an apoptotic signaling pathways both in extrinsic and intrinsic pathway. In addition, nano-ß-TCP blocked cell cycle of HepG2 cells in G0/G1 phase and disturbed expression of some related cyclins. In vivo results showed that 40 mg/kg of nano-ß-TCP had no significant toxic side effects, but could effectively suppress hepatocellular carcinoma growth. Conclusion: These findings revealed the anticancer effect of nano-ß-TCP and also clarified the mechanism of its inhibitory effect on hepatocellular carcinoma.


Assuntos
Fosfatos de Cálcio/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
Pharm Res ; 36(8): 115, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161432

RESUMO

PURPOSE: Fibrin gels (FBGs) are potential delivery vehicles for many drugs, and can be easily prepared from purified components. We previously demonstrated their applicability for the release of different doxorubicin (Dox) nanoparticles used clinically or in an experimental stage, such as its inclusion complex with the amino ß-cyclodextrin polymer (oCD-NH2/Dox). Here we extend these studies by in vitro and in vivo evaluations. METHODS: An in vitro cytotoxicity model consisting of an overlay of a neuroblastoma (NB) cell-containing agar layer above a drug-loaded FBG layer was used. Local toxicity in vivo (histology and blood analysis) was studied in a mouse orthotopic NB model (SHSY5YLuc+ cells implanted into the left adrenal gland). RESULTS: In vitro data show that FBGs loaded with oCD-NH2/Dox have a slightly lower cytotoxicity against NB cell lines than those loaded with Dox. Fibrinogen (FG), and Ca2+ concentrations may modify this activity. In vivo data support a lower general and local toxicity for FBGs loaded with oCD-NH2/Dox than those loaded with Dox. CONCLUSION: Our results suggest a possible increase of the therapeutic index of Dox when locally administered through FBGs loaded with oCD-NH2/Dox, opening the possibility of using these releasing systems for the treatment of neuroblastoma.


Assuntos
Antineoplásicos/farmacologia , Celulose/química , Ciclodextrinas/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Fibrina/química , Nanopartículas/química , Neuroblastoma/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/sangue , Portadores de Fármacos/toxicidade , Feminino , Géis , Xenoenxertos , Humanos , Camundongos Nus , Nanopartículas/toxicidade
14.
Int J Nanomedicine ; 14: 3571-3582, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213799

RESUMO

Background: In vivo fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window using organic fluorophores has great advantages, but generally suffers from a relatively low fluorescence quantum yield (mostly less than 2%). In this study, organic nanoparticles (L1013 NPs) with a high fluorescence quantum yield (9.9%) were systhesized for in vivo imaging. Methods: A molecule (BTPPA) with donor-acceptor-donor structure and aggregation-induced emission enabling moieties was prepared. BTPPA molecules were then encapsulated into nanoparticles (L1013 NPs) using a nanoprecipitation method. The L1013 NPs were intravenously injected into the mice (including normal, stroke and tumor models) for vascular and tumor imaging. Results: L1013 NPs excited at 808 nm exhibit NIR-II emission with a peak at 1013 nm and an emission tail extending to 1400 nm. They have a quantum yield of 9.9% and also show excellent photo/colloidal stabilities and negligible in vitro and in vivo toxicity. We use L1013 NPs for noninvasive real-time visualization of mouse hindlimb and cerebral vessels (including stroke pathology) under a very low power density (4.6-40 mW cm‒2) and short exposure time (40-100 ms). Moreover, L1013 NPs are able to localize tumor pathology, with a tumor-to-normal tissue ratio of 11.7±1.3, which is unusually high for NIR-II fluorescent imaging through passive targeting strategy. Conclusion: L1013 NPs demonstrate the potential for a range of clinical applications, especially for tumor surgery.


Assuntos
Corantes Fluorescentes/química , Nanopartículas/química , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Vasos Sanguíneos/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Modelos Animais de Doenças , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacocinética , Camundongos Endogâmicos C57BL , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Acidente Vascular Cerebral/diagnóstico por imagem , Distribuição Tecidual
15.
Int J Nanomedicine ; 14: 3875-3892, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213807

RESUMO

Multipotent mesenchymal stem cells have shown great promise for application in regenerative medicine owing to their particular therapeutic effects, such as significant self-renewability, low immunogenicity, and ability to differentiate into a variety of specialized cells. However, there remain certain complicated and unavoidable problems that limit their further development and application. One of the challenges is to noninvasively monitor the delivery and biodistribution of transplanted stem cells during treatment without relying on behavioral endpoints or tissue histology, and it is important to explore the potential mechanisms to clarify how stem cells work in vivo. To solve these problems, various nanoparticles (NPs) and their corresponding imaging methods have been developed recently and have made great progress. In this review, we mainly discuss NPs used to label stem cells and their toxic effects on the latter, the imaging techniques to detect such NPs, and the current existing challenges in this field.


Assuntos
Células-Tronco Mesenquimais/citologia , Nanopartículas/toxicidade , Medicina Regenerativa , Morte Celular/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Imagem Molecular , Imagem Multimodal
16.
Int J Nanomedicine ; 14: 3911-3928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213808

RESUMO

Background: Several in vitro studies have revealed that zinc oxide nanoparticles (ZnO-NPs) were able to target cancerous cells selectively with minimal damage to healthy cells. Purpose: In the current study, we aimed to evaluate the antitumor activity of ZnO-NPs in Ehrlich solid carcinoma (ESC) bearing mice by measuring their effect on the expression levels of P53, Bax and Bcl2 genes as indicators of apoptotic induction in tumor tissues. Also, we assessed the potential ameliorative or potentiation effect of 100 mg/kg N-acetyl cysteine (NAC) in combination with ZnO-NPs. Materials and methods: ESC bearing mice were gavaged with three different doses of ZnO-NPs (50, 300 and 500 mg/kg body weight) alone or in combination with NAC for seven consecutive days. In addition to measuring the tumor size, pathological changes, zinc content, oxidative stress biomarkers and DNA damage in ESC, normal muscle, liver and kidney tissues were assessed. Results: Data revealed a significant reduction in tumor size with a significant increase in p53 and Bax and decrease in Bcl2 expression levels in the tissues of ZnO-NPs treated ESC bearing mice. Moreover, a significant elevation of MDA accompanied with a significant reduction of CAT and GST. Also, a marked increase in all comet assay parameters was detected in ZnO-NPs treated groups. On the other hand, the combined treatment with ZnO-NPs and NAC significantly reduced reactive oxygen species production and DNA damage in liver and kidney tissues in all ZnO-NPs treated groups. Conclusion: ZnO-NPs exhibited a promising anticancer efficacy in ESC, this could serve as a foundation for developing new cancer therapeutics. Meanwhile, the combined treatment with ZnO-NPs and NAC could act as a protective method for the healthy normal tissue against ZnO-NPs toxicity, without affecting its antitumor activity.


Assuntos
Acetilcisteína/farmacologia , Apoptose , Nanopartículas/toxicidade , Neoplasias/patologia , Estresse Oxidativo , Óxido de Zinco/toxicidade , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspase 3/metabolismo , Dano ao DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Especificidade de Órgãos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo
17.
Aquat Toxicol ; 213: 105195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203167

RESUMO

Titanium dioxide nanoparticles (n-TiO2) are among the man-made nanomaterials that are predicted to be found at high concentrations in the aquatic environment. There, they likely co-exist with other chemical pollutants. Thus, n-TiO2 and other chemical pollutants can be taken up together or accumulate independently from each other in prey organisms of fish. This can lead to dietary exposure of fish to n-TiO2-chemical pollutant mixtures. In this study, we examine if simultaneous dietary exposure to n-TiO2 and 3,3',4,4'-Tetrachlorobiphenyl (PCB77) -used as a model compound for persistent organic pollutants with dioxin-like properties- can influence the uptake and toxicological response elicited by the respective other substance. Juvenile brown trout (Salmo trutta) were fed custom-made food pellets containing n-TiO2, PCB77 or n-TiO2+PCB77 mixtures for 15 days. Ti and PCB77 concentrations in the liver were measured by ICP-MS and GC-MS, respectively. Besides, n-TiO2 uptake was assessed using TEM. Combination effects on endpoints specific for PCB77 (i.e., cytochrome P450 1A (CYP1A) induction) and endpoints shared by both PCB77 and n-TiO2 (i.e., oxidative stress-related parameters) were measured in intestine and liver using RT-qPCR and enzyme activity assays. The results show that genes encoding for proteins/enzymes essential for tight junction function (zo-1) and ROS elimination (sod-1) were significantly upregulated in the intestine of fish exposed to n-TiO2 and PCB77 mixtures, but not in the single-substance treatments. Besides, n-TiO2 had a potentiating effect on PCB77-induced CYP1A and glutathione reductase (GR) expression/enzyme activity in the liver. This study shows that simultaneous dietary exposure to nanomaterials and traditional environmental pollutants might result in effects that are larger than observed for the substances alone, but that understanding the mechanistic basis of such effects remains challenging.


Assuntos
Dieta , Exposição Ambiental , Nanopartículas/toxicidade , Bifenilos Policlorados/toxicidade , Titânio/toxicidade , Truta/fisiologia , Animais , Biomarcadores/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Comportamento Alimentar , Regulação da Expressão Gênica/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Metalotioneína/metabolismo , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Poluentes Químicos da Água/toxicidade
18.
Environ Sci Pollut Res Int ; 26(23): 24121-24131, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31228067

RESUMO

Although iron oxide occurs naturally in the environment, iron oxide nanoparticles have distinct mobility, reactivity, and toxicity, which can harm the human health and nature. This scenario has motivated the investigation of the toxic effects of iron oxide nanoparticles (akaganeite predominance + hematite) on the aquatic plant Lemna minor. First, nanoparticles were synthesized and characterized; then, different iron oxide NP concentrations were added to Lemna minor culture. After 7 days, all the Lemna minor leaves died, irrespective of the added NP concentration. The iron oxide NP impact on the plant was evaluated based on malondialdehyde (MDA) production from thiobarbituric acid reactive substances (TBARS), which was dose-dependent; i.e., lipid peroxidation in the plant increased with rising iron oxide NP concentration. The chlorophyll content decreased at high iron oxide NP concentrations, which disrupted the light absorption mechanism. Fe accumulation in Lemna minor roots also occurred, which can harm nutrient uptake. Therefore, the iron oxide NP toxic impact on plants and related ecosystems requires further studies in order to prevent environmental damage.


Assuntos
Araceae/efeitos dos fármacos , Compostos Férricos/toxicidade , Nanopartículas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade , Araceae/metabolismo , Clorofila/metabolismo , Clorofila A/metabolismo , Ferro/farmacocinética , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Nanopartículas/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Poluentes Químicos da Água/química
19.
Environ Sci Pollut Res Int ; 26(21): 22069-22081, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31147998

RESUMO

The importance of studies on photoactive zinc oxide nanoparticles (ZnO NPs) increases with increasing environmental pollution. Since the ZnO NPs (and NPs in general) also pose an environmental risk, and since an understanding of the risk is still not sufficient, it is important to prevent their spread into the environment. Anchoring on phyllosilicate particles of micrometric size is considered to be a useful way to address this problem, however, so far mainly on the basis of leaching tests in pure water. In the present study, the phytotoxicity of kaolinite/ZnO NP (10, 30, and 50 wt.%) nanocomposites in concentrations 10, 100, and 1000 mg/dm3 tested on white mustard (Sinapis alba) seedlings was found to be higher (relative lengths of roots are ~ 1.4 times lower) compared with seedlings treated with pristine ZnO NPs. The amount of Zn accumulated from the nanocomposites in white mustard tissues was ~ 2 times higher than can be expected based on the ZnO content in the nanocomposites compared with the ZnO content (100 wt.%) in pristine ZnO NPs. For the false fox-sedge (Carex otrubae) plants, the amount of Zn accumulated in roots and leaves was ~ 2.25 times higher and ~ 2.85 times higher, respectively, compared with that of the pristine ZnO NPs (with respect to the ZnO content). Increased phytotoxicity of the nanocomposites and higher uptake of Zn by plants from the nanocomposites in comparison with pristine ZnO NPs suggest that the immobilization of ZnO NPs on the kaolinite does not reduce the environmental risk.


Assuntos
Nanocompostos/toxicidade , Plantas/efeitos dos fármacos , Óxido de Zinco/toxicidade , Caulim , Nanopartículas/toxicidade , Folhas de Planta , Raízes de Plantas , Plântula
20.
Chemosphere ; 233: 579-589, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195263

RESUMO

Complex interactions have been established between nanoparticles (NPs) and heavy metals in real environments. Herein we used zebrafish embryos to investigate the influence of titanium dioxide NPs (n-TiO2) on the uptake, bioconcentration, and depuration, and toxicity of Pb. The formation of n-TiO2-Pb complexes was confirmed in an exposure suspension. An increase in Pb bioconcentration was observed in zebrafish embryos upon co-exposure to n-TiO2 and Pb; moreover, n-TiO2-Pb complexes could be found in the embryos, indicating the bioavailability of NPs. However, there was no difference in the depuration rates of Pb in the presence of n-TiO2. Metallothionein (MT) content was significantly increased upon exposure to Pb alone, and the content significantly increased even further upon co-exposure. A downregulation in the expression levels of the neurodevelopment-related genes gfap, syn2α, and elavl3 was observed in the embryos, and we also noted a reduction in the swimming speed of and the total distance traveled by the larvae. To summarize, our results indicate that n-TiO2 can act as an effective carrier of Pb to enhance its uptake, bioavailability, and toxicity in zebrafish embryos.


Assuntos
Embrião não Mamífero/fisiologia , Chumbo/toxicidade , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Disponibilidade Biológica , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Larva/metabolismo , Metalotioneína/metabolismo , Nanopartículas/toxicidade , Peixe-Zebra/metabolismo
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