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1.
Chem Commun (Camb) ; 56(8): 1255-1258, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31898700

RESUMO

Here we demonstrated that the stiffness of cationized gelatin nanoparticles determined the efficiency of RNAi in myeloid leukemia cells when the particle size and surface charges were kept constant. The siRNA delivery system with an elastic modulus of 0.87 MPa showed the largest siRNA uptake and RNAi efficiency for hard-to-transfect suspension cells.


Assuntos
Gelatina/química , Leucemia Mieloide/patologia , Nanopartículas/química , Interferência de RNA , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Células K562 , Leucemia Mieloide/tratamento farmacológico , Tamanho da Partícula , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , Propriedades de Superfície
2.
J Photochem Photobiol B ; 202: 111725, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790880

RESUMO

Photodynamic therapy (PDT) is an expanding treatment modality due to its minimally invasive localized activity and few adverse effects. This therapy requires photosensitive compounds, which have high sensitivity to light exposure. Thus, in this work, the in vitro antitumor activity of meso-tetra(3- and 4-pyridyl)porphyrins (3-TPyP and 4-TPyP) in metastatic melanoma cell (WM1366 line) and non-tumoral Ovarian lineage Chinese Hamister (CHO) was evaluated using photodynamic process. Cell viability tests, molecular docking, annexin V, confocal microscopy and qRT-PCR were performed. Our results show that both porphyrins inhibited the viability of metastatic melanoma cells when exposed to light and did not alter viability in the dark. In addition, they did not demonstrate cytotoxicity in non-tumor cells. Molecular coupling demonstrated platinum porphyrin affinity for the N-terminal region of APO B-100, LDL receptor, and therefore of the cells under study. Genes such as Caspase 3 and 9, P21, Bax / BCL2, MnSod and GSH showed increased expression. For meta isomer 3-PtTPyP treatment, caspase-9 and caspase-3 expression levels showed a 4.89 and 3.23-fold increase, respectively, while for the para isomer 4-PtTPyP, this change was 3.77 and 12.16-fold, respectively. We also observed an upregulated expression of p21, a protein well-known by its action in cell cycle arrest in a p53-dependent manner. Conclusion: 3-PtTPyP and 4-PtTPyP demonstrated antitumor effect on WM1366 cells, inducing apoptosis and significant alteration of cell cytoskeleton actin. Our work shows that platinum(II) porphyrins may be promising photosensitizers for the treatment of metastatic melanoma by PDT.


Assuntos
Portadores de Fármacos/química , Fármacos Fotossensibilizantes/química , Platina/química , Porfirinas/química , Animais , Apoptose/efeitos dos fármacos , Sítios de Ligação , Células CHO , Caspase 3/genética , Caspase 3/metabolismo , Cátions/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Luz , Melanoma/metabolismo , Melanoma/patologia , Simulação de Acoplamento Molecular , Fármacos Fotossensibilizantes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
3.
Water Res ; 170: 115310, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770648

RESUMO

Electrodeionization (EDI) is membrane-based desalination utilizing ion exchange membranes and ion exchange resins. By combining Electrodialysis and Ion exchanger, EDI can produce ultrapure water in a continuous-flow manner. Although its theoretical mechanisms are well documented, there is no experimental platform that can provide microscopic details inside of the system. In this paper, we present microscale EDI that can visualize in situ ion concentration, pH, and fluid flows. The platform was fabricated by filling ion exchange resins as a monolayer in a transparent polydimethylsiloxane channel between cation and anion exchange membranes. According to operating voltages (0-15V), distinct behaviors of ion concentration profile, pH shift, and fluid flows were observed in Ohmic, limiting, and overlimiting regimes. It is noteworthy that overlimiting regimes can be sub-categorized as water-splitting and electroconvection regimes. In the early stage (4-8V), water-splitting is dominant with pH change near the membranes and resins; under a higher voltage (8-15V), electroconvection starts to occur even water-splitting tries to suppress the development of the extended space charge layer and corresponding electroconvective instability. Accelerated ionic migration by electroconvection can improve current efficiency up to 80%. This is a clear departure from overlimiting dynamics in electrodialysis (with electroconvection only), ion exchanger (with no distinct regime), and even from that in previous EDI experiments (with water splitting only).


Assuntos
Membranas Artificiais , Água , Ânions , Cátions , Troca Iônica
4.
Water Res ; 170: 115346, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31801097

RESUMO

Ballasted flocculation is an efficient high-rate sedimentation process getting more attention as an advanced P removal technology for levels below 0.1 mg/L. The process is well-known yet only very few studies have investigated the interactions, within the matrix of wastewater, of coagulant, polymer and ballast, especially when it comes to polymer doses and types which are, in the industry, rather based on recommendations than scientific evidence. In this work, the impact of anionic and cationic polymers has been investigated on P removal and floc properties. Anionic polymers showed to be superior to cationic ones when it comes to P removal and doses even as low as 0.01 mg/L yield better results than coagulant alone. There appears to be a "best-case" floc size with which very good P removal (>90%) can be achieved and flocs of sufficient strength can be generated.


Assuntos
Águas Residuárias , Purificação da Água , Ânions , Cátions , Floculação , Polímeros
5.
J Chem Theory Comput ; 16(1): 738-748, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31762275

RESUMO

Phosphatidylserine (PS) lipids are important signaling molecules and the most common negatively charged lipids in eukaryotic membranes. The signaling can be often regulated by calcium, but its interactions with PS headgroups are not fully understood. Classical molecular dynamics (MD) simulations can potentially give detailed description of lipid-ion interactions, but the results strongly depend on the used force field. Here, we apply the electronic continuum correction (ECC) to the Amber Lipid17 parameters of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (POPS) lipid to improve its interactions with K+, Na+, and Ca2+ ions. The partial charges of the headgroup, glycerol backbone, and carbonyls of POPS, bearing a unit negative charge, were scaled with a factor of 0.75, derived for monovalent ions, and the Lennard-Jones σ parameters of the same segments were scaled with a factor of 0.89. The resulting ECC-POPS model gives more realistic interactions with Na+ and Ca2+ cations than the original Amber Lipid17 parameters when validated using headgroup order parameters and the "electrometer concept". In ECC-lipids simulations, populations of complexes of Ca2+ cations with more than two PS lipids are negligible, and interactions of Ca2+ cations with only carboxylate groups are twice more likely than with only phosphate groups, while interactions with carbonyls almost entirely involve other groups as well. Our results pave the way for more realistic MD simulations of biomolecular systems with anionic membranes, allowing signaling processes involving PS and Ca2+ to be elucidated.


Assuntos
Cálcio/metabolismo , Bicamadas Lipídicas/metabolismo , Fosfatidilserinas/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Cátions/metabolismo , Elétrons , Simulação de Dinâmica Molecular
6.
Food Chem ; 308: 125647, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31648088

RESUMO

An analyser was constructed on the basis of on-line connection of capillary electrophoresis over a short separation path with continuous mini-dialysis sample collection. The developed instrument was employed for simultaneous determination of the majority minerals K+, Ca2+, Na+ and Mg2+ (and possibly NH4+ ions) in commercially available unflavoured yoghurts. The cations are released from the organic structures by digestion with boiling 6 mol/L HCl. They were separated from residues of the organic matrix by a dialysis probe and were transferred to a stream of water. From the continuous stream, the dialysate was injected into the separation capillary through a flow-gating interface. Within the reliability interval, the determined total mineral content was equal to their contents stated on the yoghurt labels and the content determined by flame atomic absorption spectrometry and complexometric titration. The relative standard deviation of the electrophoretic determination is mostly about 5%.


Assuntos
Iogurte/análise , Cátions/química , Diálise , Eletroforese Capilar/métodos , Reprodutibilidade dos Testes , Espectrofotometria Atômica , Fatores de Tempo , Água/análise
7.
Ecotoxicol Environ Saf ; 187: 109836, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31675504

RESUMO

Toxicity of 13 ionic liquids (ILs) corresponding to different families were studied by inhibition respiration assays (15 min) using activated sludge. Toxicity increased as increasing the number of carbons in the alkyl-chain of imidazolium-based ILs, with EC50 values from 4.19 to 0.17 for 1-ethyl-3-methylimidazolium chloride ([Emim][Cl]) and 1-octyl-3-methylimidazolium chloride ([Omim][Cl]), respectively. An increase in toxicity was observed for aromatic-based ILs (pyridinium- and imidazolium-based ILs) due to the hydrophobic character of the head groups in comparison with linear structures as phosphonium and ammonium cations. Among to the anions studied fixing [Emim]+ as cation, [HSO4]- and [NTf2]- presented low EC50 values (0.34 mM and 1.69 mM, respectively) while [Cl]- and [EtSO4]- were considered harmless anions due to the hydrophilic character of chloride and the organic nature of [EtSO4]-. ILs toxicity/inhibition was determined by adding a biodegradable compound and measuring the sludge response after being in contact with the ILs for at least 15 h. The exposure of sewage sludge to ILs for more than 15 min used in short inhibition assays caused more toxic effect on microorganisms, even for [Choline][NTf2], previously defined as practically harmless (EC50 = 2.79 mM). Biodegradability assays confirmed the biodegradable nature of choline cation, related with TOC conversion of 40%, only due to cation consumption. No oxygen consumption or even lysis of microbial cells was observed for Tetrabutylammonium bis(trifluoromethylsulfonyl)imide and for 1-Ethyl-3-methylimidazolium hydrogensulphate due to the presence of anions previously defined as hazardous ([NTf2]- and [HSO4]-), maintaining their recalcitrant character to sewage systems.


Assuntos
Imidazóis/toxicidade , Líquidos Iônicos/toxicidade , Esgotos/microbiologia , Ânions , Biodegradação Ambiental , Cátions , Interações Hidrofóbicas e Hidrofílicas , Imidazóis/química , Líquidos Iônicos/química , Estrutura Molecular
8.
J Photochem Photobiol B ; 203: 111739, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855719

RESUMO

A mono-N-substituted probe L containing a bromosalicylaldehyde pendant arm attached to a tetraazamacrocyclic "tet a" moiety was synthesized via straight forward reaction. The probe L crystallizes in a monoclinic P21/n space group. The probe L displayed quick sensitivity and selectivity towards Hg2+ ions due to its hopeful Chelation Enhancement Quenching (CHEQ) feature. Interestingly, the probe L exhibits turn-off fluorescence response to Hg2+ ion and turn-on fluorescence signals to HSO4- ions. When the probe L was complexed with HSO4- in 1:1 mode (L + HSO4- formation), improved turn-on fluorescence emission was detected due to the chelation enhanced fluorescence effect through sensor complex. The macrocyclic "tet a" probe L exhibited a binding constant value of 3.89 × 106 M-1 and 5.58 × 105 M-1 for Hg2+ and HSO4-, respectively. Probe L exhibited good selectivity to Hg2+ rather than other common metal ions and HSO4- over other common anions. The limit of detection (LOD) of Hg2+ and HSO4- were found to be 1 nM and 7 µM, respectively. The time-resolved fluorescence emission single-photon counting study was used to determine the average lifetime value for the probe L and L + HSO4- ions as 0.47 and 1.02 ns, respectively. The practical application of the probe in visualizing intracellular Hg2+ and HSO4- ions distribution in live Artemia salina was demonstrated. Furthermore, the probe L with Hg2+cations was found to be cytotoxic against breast cancer cells in nature and can be delivered as an anticancer agent. Besides the probe L with HSO4- exhibit strong fluorescence emission with low cytotoxicity, and it can be recommended for live-cell imaging.


Assuntos
Corantes Fluorescentes/química , Compostos Macrocíclicos/química , Mercúrio/análise , Microscopia de Fluorescência/métodos , Sulfitos/análise , Animais , Ânions/química , Artemia/crescimento & desenvolvimento , Cátions/química , Linhagem Celular Tumoral , Humanos , Larva/química , Larva/metabolismo , Limite de Detecção , Conformação Molecular
9.
Chemosphere ; 238: 124656, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472345

RESUMO

A composite sorbent for the simultaneous removal of both Hg2+ and SeO32- from aqueous media was produced from the solvothermal synthesis of a zirconium metal organic framework, UiO-66, in the presence of activated carbon. The composite sorbent has a large surface area of 1051 m2 g-1 with crystalized porous structures and has strong thermal stability up to 600 °C. The contaminant uptake of the sorbent follows a Langmuir adsorption isotherm with maximum sorption capacity of 205 mg g-1 and 168 mg g-1 for Hg2+ and SeO32-, respectively. Scanning electron microscopy-energy dispersive spectroscopy results show that the Se regions overlap exclusively with Zr-rich regions suggesting that SeO32- adsorption depends entirely on the exposed UiO-66 surface. In addition, X-ray photoelectron spectroscopy spectra of Se 3d and Hg 4f showed the association of SeO32- and Hg2+ on the UiO-66 and carbon surfaces, respectively. The sorbent could facilitate the development of a single process for the simultaneous removal of cationic Hg and anionic Se as well as other similar ionic metals with opposite charges from aqueous media.


Assuntos
Adsorção , Carvão Vegetal/química , Estruturas Metalorgânicas/química , Metais/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Ânions , Cátions , Mercúrio/química , Mercúrio/isolamento & purificação , Óxidos de Selênio/isolamento & purificação , Poluentes Químicos da Água/química , Zircônio/química
10.
Chemosphere ; 238: 124664, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472349

RESUMO

Chemosensors have already demonstrated potential for the detection and imaging of metal ions in solutions and biological systems, however, their applications to soil analysis are limited. This study explores the potential of utilizing a chemosensor for the detection of exchangeable Cu2+ in soils via qualitative (solution visual color change) and quantitative (UV-Vis spectrophotometry) approaches. Montmorillonite and kaolin clays were doped with Cu(NO3)2 solutions from 2.5 to 50 mM, and contaminated soil samples were collected from a historic copper mine. The exchangeable Cu2+ was extracted using a standard CaCl2 cation exchange approach, and the Cu2+ concentration in the resulting solutions determined by UV-Vis spectrophotometry, using a chemosensor, and compared to traditional ICP-MS analysis. Analytical results showed that the chemosensor provided a visual response in contaminated soils at concentrations of 25 µM and quantitative detection to concentrations of 1 µM using UV-Vis spectrophotometry. This work demonstrates the first reported chemosensor for exchangeable Cu2+ with application to soil systems.


Assuntos
Colorimetria/métodos , Cobre/análise , Poluentes do Solo/análise , Bentonita/química , Cátions , Argila/química , Mineração , Solo , Espectrofotometria
11.
Chemosphere ; 239: 124741, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31518921

RESUMO

In many parts of the world, wastewater irrigation has become a common practice because of freshwater scarcity and to increase resource reuse efficiency. Wastewater irrigation has positive impacts on livelihoods and at the same time, it has adverse impacts related to environmental pollution. Hydrochemical processes and groundwater behaviour need to be analyzed for a thorough understanding of the geochemical evolution in the wastewater irrigated systems. The current study focuses on a micro-watershed in the peri-urban Hyderabad of India, where farmers practice intensive wastewater irrigation. To evaluate the major factors that control groundwater geochemical processes, we analyzed the chemical composition of the wastewater used for irrigation and groundwater samples on a monthly basis for one hydrological year. The groundwater samples were collected in three settings of the watershed: wastewater irrigated area, groundwater irrigated area and upstream peri-urban area. The collected groundwater and wastewater samples were analyzed for major anions, cations and nutrients. We systematically investigated the anthropogenic influences and hydrogeochemical processes such as cation exchange, precipitation and dissolution of minerals using saturated indices, and freshwater-wastewater mixtures at the aquifer interface. Saturation indices of halite, gypsum and fluorite are exhibiting mineral dissolution and calcite and dolomite display mineral precipitation. Overall, the results suggest that the groundwater geochemistry of the watershed is largely controlled by long-term wastewater irrigation, local rainfall patterns and water-rock interactions. The study results can provide the basis for local decision-makers to develop sustainable groundwater management strategies and to control the aquifer pollution influenced by wastewater irrigation.


Assuntos
Irrigação Agrícola/métodos , Água Subterrânea/química , Águas Residuárias , Ânions/análise , Carbonato de Cálcio/química , Sulfato de Cálcio/química , Cátions/análise , Meio Ambiente , Monitoramento Ambiental/métodos , Água Doce/química , Água Subterrânea/análise , Hidrologia/métodos , Índia , Magnésio/química , Salinidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Qualidade da Água
12.
Chemosphere ; 239: 124840, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31526996

RESUMO

Organic-magnetic bentonites (OMBts), i.e., amphoteric modified MBt (BS-MBt), amphoteric-cationic modified MBt (BS-CT-MBt) and amphoteric-anionic modified MBt (BS-SDS-MBt), obtained by modifying magnetic bentonite (MBt) with amphoteric surfactant (BS), cationic surfactant (CT) and anionic surfactant (SDS) were investigated with the aim to remove cadmium (Cd2+). The modifier contents, surface charge and Cd2+ adsorption performances of OMBts were compared, and the influences of pH, temperature and ionic strength on Cd2+ removal were evaluated. Results showed that modifier contents of OMBts increased in the order: BS-CT-MBt > BS-MBt > BS-SDS-MBt. Although CEC of adsorbents increased in the order: MBt > BS-MBt > BS-SDS-MBt > BS-CT-MBt. The BS-MBt exhibited the highest Cd2+ adsorption capacity (233.19 mmol kg-1) than other adsorbents. The adsorption isotherms could be well described by Langmuir model. The Cd2+ adsorption capacities on MBt and OMBts increased with an increase in pH, temperature and with a decrease of ionic strength. According to characterizations (FT-IR and XPS) and experiments, Cd2+ adsorption on MBt and OMBts most possibly involved electrostatic interaction, ion exchange, and surface complexation. Furthermore, the adsorption of Cd2+ on BS-MBt was also attributed to the chelation. The amidocyanogen group of BS-CT-MBt inhibited adsorption of Cd2+ due to electrostatic repulsion, while Cd2+ was adsorbed on BS-SDS-MBt through electrostatic attraction induced by the sulfo group.


Assuntos
Bentonita/química , Cádmio/isolamento & purificação , Tensoativos/química , Adsorção , Ânions , Cádmio/química , Cátions , Concentração de Íons de Hidrogênio , Fenômenos Magnéticos , Concentração Osmolar , Eletricidade Estática , Temperatura Ambiente , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação
13.
Chemosphere ; 239: 124730, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726518

RESUMO

The impact of electrolytes on the adsorption of emerging pollutants: pharmaceuticals onto layered materials: a raw clay mineral and its nonionic and cationic organoclay derivatives was studied. The selected pharmaceuticals: amoxicillin, norfloxacin, sulfamethoxazole, metoprolol, carbamazepine, and trimethoprim show different electric charges: zwitterionic, anionic, cationic and neutral and hydrophobic character (different LogP). Without any salts, the set of complementary data obtained by UV and infrared spectroscopies, X-ray diffraction points out the importance of the electric charge which represents a key parameter in both the spontaneity and feasibility of the adsorption. In contrast, the hydrophobicity of the analytes plays a minor role but determines the magnitude of the adsorbed amount of pharmaceuticals onto organoclays. With a dual hydrophilic and hydrophobic behavior, nonionic organoclay appears to be the most polyvalent material for the removal of the pharmaceuticals. In the presence of electrolytes (NaCl at a concentration of 1 × 10-2 mol L-1), both nonionic and cationic organoclays show a decrease of their efficiencies, whereas the adsorption is particularly enhanced for Na-Mt except for the cationic species (trimethoprim and metoprolol). Thus, in realistic experimental conditions close to those of natural effluents, raw clay mineral appears as the most appropriate sorbent for the studied pharmaceuticals while it raises the question of the usefulness of organoclays in water remediation strategy.


Assuntos
Eletrólitos/química , Recuperação e Remediação Ambiental/métodos , Preparações Farmacêuticas/análise , Poluentes do Solo/análise , Solo/química , Poluentes Químicos da Água/análise , Adsorção , Amoxicilina/análise , Amoxicilina/química , Carbamazepina/análise , Carbamazepina/química , Cátions/análise , Interações Hidrofóbicas e Hidrofílicas , Metoprolol/análise , Metoprolol/química , Norfloxacino/análise , Norfloxacino/química , Preparações Farmacêuticas/química , Poluentes do Solo/química , Sulfametoxazol/análise , Sulfametoxazol/química , Trimetoprima/análise , Trimetoprima/química , Água/química , Poluentes Químicos da Água/química , Difração de Raios X
14.
J Phys Chem Lett ; 10(24): 7577-7585, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31769690

RESUMO

Guanine(G)-rich human telomeric (HT) DNA repeats, crucial to maintenance of genome stability, readily form G-quadruplexes (GQs) with various folding topologies. Research on excitation dynamics of HT-GQs is, however, scarce. Herein, we report a femtosecond time-resolved fluorescence coupled with transient absorption investigation on HT-GQ with the basket-type structure in Na+ solution. The result unveils an unusual multichannel nonradiative mechanism dominated by states with varying character of charge transfer lasting ten and hundreds of picoseconds, accounting altogether for an overwhelming ∼85% of the overall deactivation involving proton transfer. Our comparative study shows that encapsulating the GQ in nanocavity water pool or changing it into hydrid-type topologies with the presence of K+ ions alter differently energies and lifetimes of these states, yet without affecting the nature of the electronic excitation involved. The finding of this work underscores a leading role of structural rigidity in regulating the interplay with the microenvironment of photoexcited monomolecularly folded HT-GQs.


Assuntos
DNA/química , Quadruplex G , Metais/química , Nanoestruturas/química , Telômero/química , Sequência de Bases , Cátions/química , Corantes Fluorescentes/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Luz , Processos Fotoquímicos , Espectrometria de Fluorescência/métodos , Água/química
15.
J Biomed Nanotechnol ; 15(12): 2428-2438, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748022

RESUMO

Limited understanding of mitochondria disorders that induced by nanoparticles is a stumbling block for anti-cancer drug delivery targeting strategy. In present study, C6 glioma cells were exposed to aminated and alkylated SiO2 nanoparticles for mitochondrion disordering and cell metabolism study. Collective results showed that aminated nanoparticles tend to trigger the cell-repair mechanism in cancer cells while alkylated nanoparticles could cause irreversible damages on cancer cells, although both types of the particles were proved to damage mitochondrion. The underlying mechanism show that aminated nanoparticles induced proton-stuck effect in mitochondrion and self-repairing in cancer cells by up-regulating p21. Otherwise, alkylated nanoparticles damaged mitochondrion and induced phosphorylated cyclin E accumulation lead to Fbw7 down-regulation caused further S phase arrest and severe late apoptosis. This work can help us elucidate the mechanism of the clinic application of nano-drug carriers.


Assuntos
Nanopartículas , Apoptose , Cátions , Linhagem Celular Tumoral , Humanos , Mitocôndrias , Dióxido de Silício
16.
Int J Nanomedicine ; 14: 8345-8360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695371

RESUMO

Background: The protective role of puerarin (PUE) against myocardial infarction is closely related to its regulation on mitochondria. However, free PUE can hardly reach the mitochondria of ischemic cardiomyocytes due to the lack of mitochondrial targeting of PUE. Here PUE was loaded into mitochondria-targeted micelles (PUE@TPP/PEG-PE) for precisely delivering PUE into mitochondria with the aim of enhancing the anti-apoptosis effect. Methods: The mitochondriotropic polymer TPP-PEG-PE was synthesized for the preparation of PUE@TPP/PEG-PE micelles modified with triphenylphosphonium (TPP) cation. The physicochemical properties and anti-apoptosis effect of PUE@TPP/PEG-PE micelles were investigated. The coumarin 6 (C6)-labeled TPP/PEG-PE (C6@TPP/PEG-PE) micelles were used to observe the enhanced cellular uptake, mitochondrial targeting and lysosomes escape. Moreover, in vivo and ex vivo biodistribution of lipophilic near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR)-labeled PUE@TPP/PEG-PE (DiR@TPP/PEG-PE) micelles were detected through fluorescence imaging. Results: The successful synthesis of TPP-PEG-PE conjugate was confirmed. PUE@TPP/PEG-PE micelles had a particle size of 17.1 nm, a zeta potential of -6.2 mV, and a sustained-release behavior. The in vitro results showed that the intracellular uptake of C6@TPP/PEG-PE micelles was significantly enhanced in H9c2 cells. C6@TPP/PEG-PE micelles could deliver C6 to mitochondria and reduce the capture of lysosomes. In addition, compared with the PUE@PEG-PE micelles and free PUE, the PUE@TPP/PEG-PE micelles exerted an enhanced protective effect against isoprenaline-induced H9c2 cell apoptosis, as evident by the decreased percentage of apoptotic cells, Caspase-3 activity, ROS level, Bax expression, and increased Bcl-2 expression. The in vivo detecting results of the targeting effect using DiR probe also indicated that TPP/PEG-PE micelles could accumulate and retain in the ischemic myocardium. Conclusion: The results of this study demonstrate the promising potential of applying PUE@TPP/PEG-PE micelles in mitochondria-targeted drug delivery to achieve maximum therapeutic effects of PUE.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Isoflavonas/farmacologia , Micelas , Mitocôndrias/metabolismo , Miócitos Cardíacos/patologia , Fosfinas/química , Animais , Cátions , Linhagem Celular , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Isoproterenol , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos , Eletricidade Estática , Distribuição Tecidual/efeitos dos fármacos
17.
J Basic Microbiol ; 59(12): 1238-1247, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31613018

RESUMO

Penicillium griseoroseum lectin was 80-fold purified by successive DEAE Sepharose anion exchange and Sephadex G-100 gel permeation chromatography. P. griseoroseum lectin exhibited haemagglutination activity towards protease-treated rabbit erythrocytes. It showed specificity towards various carbohydrates such as d-mannose, N-acetyl-d-glucosamine, mucins, and so forth. P. griseoroseum lectin was found as a glycoprotein with glycan content of 4.33%. Purified P. griseoroseum lectin is homodimeric having a molecular mass of 57 kDa with subunit molecular mass of 28.6 kDa. Haemagglutination activity of purified P. griseoroseum lectin was completely stable from 25°C to 35°C at a pH range of 6-7.5. Lectin activity was not influenced by divalent metal ions and denaturants. P. griseoroseum lectin manifested mitogenicity towards mice splenocytes and activity reached a peak at 75 µg/ml of lectin concentration. P. griseoroseum lectin in microgram concentrations stimulated proliferation of mice splenocytes. Thus, P. griseoroseum lectin exhibits potential mitogenicity, which can be exploited for further biomedical applications.


Assuntos
Lectinas/química , Lectinas/isolamento & purificação , Mitógenos/química , Mitógenos/isolamento & purificação , Penicillium/química , Animais , Carboidratos/química , Cátions/metabolismo , Proliferação de Células/efeitos dos fármacos , Quelantes , Glicoproteínas/química , Hemaglutinação , Concentração de Íons de Hidrogênio , Lectinas/farmacologia , Masculino , Camundongos , Mitógenos/farmacologia , Peso Molecular , Multimerização Proteica , Estabilidade Proteica , Temperatura Ambiente
18.
Inorg Chem ; 58(21): 14626-14634, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31613591

RESUMO

The special linear dioxo cation structure of the uranyl cation, which relegates ligand coordination to an equatorial plane perpendicular to the O═U═O vector, poses an unusual challenge for the rational design of efficient chelating agents. Therefore, the planar hexadentate ligand rational design employed in this work incorporates two bidentate catecholamine (CAM) chelating moieties and a flexible linker with a ß-dicarbonyl chelating moiety (ß-dicarbonyl(CAM)2 ligands). The solution thermodynamics of ß-dicarbonyl(CAM)2 with a uranyl cation was investigated by potentiometric and spectrophotometric titrations. The results demonstrated that the pUO22+ values are significantly higher than for the previously reported TMA(2Li-1,2-HOPO)2, and efficient chelation of the uranyl cation was realized by the planar hexadentate ß-dicarbonyl(CAM)2. The efficient chelating ability of ß-dicarbonyl(CAM)2 was attributed to the presence of the more flexible ß-dicarbonyl chelating linker and planar hexadentate structure, which favors the geometric arrangement between ligand and uranyl coordinative preference. Meanwhile, ß-dicarbonyl(CAM)2 also exhibits higher antiradical efficiency in comparison to butylated hydroxyanisole. These results indicated that ß-dicarbonyl(CAM)2 has potential application prospects as a chelating agent for efficient chelation of a uranyl cation.


Assuntos
Antioxidantes/química , Catecolaminas/química , Quelantes/química , Termodinâmica , Urânio/química , Antioxidantes/síntese química , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Catecolaminas/síntese química , Catecolaminas/farmacologia , Cátions/química , Quelantes/síntese química , Quelantes/farmacologia , Ligantes , Estrutura Molecular , Picratos/antagonistas & inibidores
19.
Int J Nanomedicine ; 14: 6575-6585, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616144

RESUMO

Background and purpose: In a past study, we developed and optimized a novel cationic PEGylated niosome containing anticancer drugs (doxorubicin or quercetin) and siRNA. This study intended to evaluate the anti-tumor effects of the combination therapy to target both the proteins and genes responsible for the development of gastric cancer. CDC20, known as an oncogene, is a good potential therapeutic candidate for gastric cancer. Methods: In order to increase the loading capacity of siRNA and achieve appropriate physical properties, we optimized the cationic PEGylated niosome in terms of the amount of the cationic lipids. Drugs (doxorubicin and quercetin) and CDC20siRNA were loaded into the co-delivery system, and physical characteristics, thermosensitive controlled-release, gene silencing efficiency, and apoptosis rate were determined. Results: The results showed that the designed co-delivery system for the drugs and gene silencer had an appropriate size and a high positive charge for loading siRNA, and also showed a thermosensitive drug release behavior, which successfully silenced the CDC20 expression when compared with the single delivery of siRNA or the drug. Moreover, the co-delivery of drugs and CDC20siRNA exhibited a highly inhibitory property for the cell growth of gastric cancer cells. Conclusion: It seems that the novel cationic PEGylated niosomes co-loaded with anticancer drug and CDC20siRNA has a promising application for the treatment of gastric cancer.


Assuntos
Proteínas Cdc20/metabolismo , Doxorrubicina/uso terapêutico , Polietilenoglicóis/química , Quercetina/uso terapêutico , RNA Interferente Pequeno/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Cátions , Proteínas Cdc20/genética , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Endocitose , Ácidos Graxos Monoinsaturados/química , Inativação Gênica/efeitos dos fármacos , Humanos , Lipossomos , Tamanho da Partícula , Compostos de Amônio Quaternário/química , Quercetina/farmacologia , RNA Interferente Pequeno/genética , Eletricidade Estática , Temperatura Ambiente
20.
J Cancer Res Clin Oncol ; 145(12): 2951-2967, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31654121

RESUMO

PURPOSE: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide and new improvements are urgently needed. Several miRNA-targeted therapeutics have reached clinical development. MicroRNA-143 (miR-143) was found to significantly suppress the migration and invasion of NSCLC. It might be of great potential for NSCLC treatment. However, the therapeutic effect of miR-143 against NSCLC in vivo has not been explored until now. METHODS: The cationic liposome/pVAX-miR-143 complex (CL-pVAX-miR-143) was prepared and its biodistribution was assessed. The tumor suppression effects of CL-pVAX-miR-143 were evaluated in early-stage and advanced experimental lung cancer metastasis mice models by systemic delivery, respectively, and also in subcutaneous tumor models by intratumoral injection. The toxicity of CL-pVAX-miR-143 was assessed by H&E analysis and biochemical measurements. The preliminary mechanism of CL-pVAX-miR-143 on tumor suppression was explored by immunochemistry and western blotting. RESULTS: The assays on the stability and safety of CL-pVAX-miR-143 showed that it mainly accumulated in the lung after systemic administration. The intratumoral delivery of CL-pVAX-miR-143 effectively inhibited A549 subcutaneous tumor growth. Notably, systemic delivery of CL-pVAX-miR-143 significantly inhibited tumor metastasis and prolonged survival dose dependently in early-stage experimental lung cancer metastasis models. More importantly, same results were shown in advanced mice models with metastasis. CL-pVAX-miR-143 treatment did not induce obvious acute toxicity. The preliminary mechanism on inhibiting tumor metastasis might be induced by targeting CD44v3. CONCLUSIONS: Our results suggested that CL-pVAX-miR-143 might be a promising strategy for clinical treatment of non-small cell lung cancer, especially for advanced NSCLC with metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cátions/administração & dosagem , Lipossomos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/administração & dosagem , Células A549 , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual
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