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1.
Artigo em Inglês | MEDLINE | ID: mdl-31479233

RESUMO

Huntington's disease (HD) is an incurable disease with progressive loss of neural function, which is influenced by epigenetic, oxidative stress, metabolic, and nutritional factors. Targeting inhibition of huntingtin protein aggregation is a strategy for HD therapy, but the efficacy is unsatisfactory. Studies found that selenium (Se) levels in the brain is insufficient for HD disease, while improvement in Se homeostasis in the brain may attenuate neuronal loss and dysfunction. In this study, we applied selenium nanoparticles (NPs) (Nano-Se) for the HD disease therapy by regulating HD-related neurodegeneration and cognitive decline based on transgenic HD models of Caenorhabditis elegans (C. elegans). At low dosages, Nano-Se NPs significantly reduced neuronal death, relieved behavioral dysfunction, and protected C. elegans from damages in stress conditions. Molecular mechanism also revealed that Nano-Se attenuated oxidative stress, inhibited the aggregation of huntingtin proteins, and down regulated the expression of histone deacetylase family members at mRNA levels. The results suggested that Nano-Se has great potential for Huntington's disease therapy. In conclusion, mechanism about how Nano-Se NPs protect from damages in stress conditions and repair neural functions will benefit to HD disease therapy. This study will also guide rational design of Nano-Se NPs or other selenium compounds to improve HD therapy in the future.

2.
Environ Pollut ; 254(Pt B): 113032, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31454581

RESUMO

Although, health and environmental hazards of Ni are ironclad; however, that of Nickle oxide nanoparticles (NiO-NPs) are still obscure. Therefore, impact of NiO-NPs exposure (0, 5, 50, 200, 500 and 1000 mg kg-1 soil) on the earthworm (Eisenia fetida) survival (at 28th day), reproduction (at 56th day), histopathology, ultrastructures, antioxidant enzymes and oxidative DNA damage was appraised in full life cycle study. Lower concentrations of NiO-NPs (5, 50 and 200) did not influence the survival, reproduction and growth rate of adult worms significantly. However, reproduction reduced by 40-50% with 500 and 1000 mg kg-1 exposure, which also induced oxidative stress leading to DNA damage in earthworms. Ultrastructural observation and histology of earthworms exposed to higher NiO-NPs concentrations revealed abnormalities in epithelium layer, microvilli and mitochondria with underlying pathologies of epidermis and muscles, as well as adverse effects on the gut barrier. To the best of our knowledge, this is the first study unveiling the adverse effects of NiO-NPs on a soil invertebrate (Eisenia fetida). Our findings clue towards looking extensively into the risks of NiO-NPs on soil organisms bearing agricultural and environmental significance.

3.
Mikrochim Acta ; 186(9): 640, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31440852

RESUMO

A fluorometric method is described for "turn-on" sensing of pH values via black phosphorus quantum dots (BPQD). Water-stable BPQD were synthesized by a liquid exfoliation method and characterized by TEM, FT-IR, XPS, and absorption and fluorescence spectra. The nanoparticles of BPQD have a uniform distribution with an average size of 5.2 nm. They exhibit bright green fluorescence, with excitation/emission maxima at 420/515 nm. The fluorescence of the BPQD is likely to arise from the quasi-molecular fluorophores of polycyclic aromatic compounds carrying P-P, P-O-P, and PxOy functions on its surface. The protonation and deprotonation of hydroxyl groups of BPQD causes a different degree of quenching of the BPQD. At pH values below 4.0, protons bind to BPQD to form non-fluorescent ground state complexes. At pH values above 4.0, the hydroxyl groups become deprotonated, and this induces the recovery of fluorescence. The sensor has a linear response in the pH range of 1.0-9.0. It was successfully applied to the determination of the pH values in human urine and serum samples. Graphical abstract Schematic representation of the preparation of black phosphorus quantum dots (BPQDs) from powdered BP crystals using liquid-phase exfoliation in N-methyl-2-pyrrolidone solution. The BPQDs display green fluorescence at high pH values but no fluorescence at very low pH values.

5.
Environ Sci Technol ; 53(15): 9128-9138, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31268311

RESUMO

The Spring Festival is the most important holiday in China. During this time, the levels of particulate matter (PM) as well as gaseous copollutants significantly increase because of the widespread enjoyment of fireworks. The expression patterns of microRNAs may serve as valuable signatures of exposure to environmental constituents. We exposed macrophages to the whole stream of outdoor air at the air-liquid interface aiming at closely approximating the physiological conditions and the inhalation situation in the lung. 58 miRNAs were up-regulated, and 68 miRNAs were down-regulated in the night of the New Year's Eve (exposure group E2N1) compared to filtered-air exposed control cells. The target genes of the up-regulated miRNAs were enriched in immunity- and inflammation-linked pathways, such as the TLR-NF-κB pathway. Compared to the E2N1 group, 29 miRNAs were up-regulated, and 23 miRNAs were down-regulated in the cells exposed to air from the daytime of the Chinese New Year with higher concentrations of particles, SO2, and nitrogen oxide. The target genes of the up-regulated miRNAs were mostly enriched in apoptosis, adhesion, and junction-related pathways. These results preliminarily unravel part of the toxic mechanisms of air constituents and provide clues for discovering the main drivers of air pollution-induced disorders.

7.
Sci Rep ; 9(1): 10255, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311980

RESUMO

Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABAB receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase-like protein 1 (GADL1) is shown to be associated with lithium response in Han Chinese BPI patients. In this study, we demonstrated for the first time the relationship among lithium, GADL1, and KCTD12. In circulating CD11b+ macrophage cells, BPI patients showed a significantly higher percentage of KCTD12 expression than healthy controls. Among BPI patients, carriers of the 'T' allele (i.e., CT or TT) at site rs17026688 were found to secrete lower amounts of GADL1 but higher amounts of GABA b receptor 2 (GABBR2) in the plasma. In human SH-SY5Y neuroblastoma cells, lithium treatment increased the percentage of KCTD12 expression. Through inhibition of glycogen synthase kinase-3 (GSK-3), lithium induced cyclic AMP-response element binding protein (CREB)-mediated KCTD12 promoter activation. On the other hand, GADL1 overexpression enhanced GSK-3 activation and inhibited KCTD12 expression. We found that lithium induced, whereas GADL1 inhibited, KCTD12 expression. These findings suggested that KCTD12 may be an important gene with respect to neuron excitability and lithium response in BPI patients. Therefore, targeting GSK-3 activity and/or KCTD12 expression may constitute a possible therapeutic strategy for treating patients with BPI disorder.

9.
Bioconjug Chem ; 30(7): 1923-1937, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31259537

RESUMO

The formation of a protein corona has been considered a pitfall in the clinical translation of nanomedicines. Hence, interdisciplinary studies on corona characterization are critically essential. A deep understanding of the formation of hard and soft protein coronas upon in vivo administration of nanoparticles is vital. The protein corona gives the nanoplatform a new biological identity. Furthermore, the control of and mechanistic understanding of corona formation as it is regulated by the physicochemical properties of nanoparticles is crucial for developing safe nanomedicines. A growing number of analytical techniques have been developed in the past decade for examining NP-protein interactions, contributing to a better understanding of protein corona formation on the surface of nanoparticles. In this Review, we summarize the latest developments in the in vivo and in vitro study of dynamic protein corona formation. Insights derived from techniques used to visualize, quantify, and define protein coronas, as well as the methods for examining the kinetics and structural changes of coronal proteins, are discussed. The potential challenges and future perspectives in the study of protein corona formation and its effects on biological behavior and applications of therapeutic nanomaterials are also provided.

10.
ACS Nano ; 13(8): 8680-8693, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31329416

RESUMO

When nanoparticles interact with cellular or organelle membranes, the coating ligands are known to affect the integrity of the membranes, which regulate cell death and inflammation. However, the molecular mechanisms of this modulation remain unresolved. Here, we use synchrotron X-ray liquid surface scattering and molecular dynamics simulations to study interface structures between phospholipids and gold nanorods (AuNRs) coated by surfactant and polyelectrolyte. These ligands are two types of widely used surface modification with different self-assembled structures and stabilities on the surface of nanoparticles. We reveal distinct mechanisms of the ligand stability in disrupting membrane integrity. We find that the cationic surfactant ligand cetyltrimethylammonium bromide detaches from the AuNRs and inserts into phospholipids, resulting in reduced membrane thickness by compressing the phospholipids to align with the shorter ligand. Conversely, the cationic polyelectrolyte ligand poly(diallyldimethylammonium chloride) is more stable on AuNRs; although it adsorbs onto the membrane, it does not cause much impairment. The distinct coating ligand interactions with phospholipids are further verified by cellular responses including impaired lysosomal membranes and triggered inflammatory effects in macrophages. Together, the quantitative analysis of interface structures elucidates key bio-nano interactions and highlights the importance of surface ligand stability for safety and rational design of nanoparticles.

11.
Acc Chem Res ; 52(6): 1507-1518, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31149804

RESUMO

Engineered nanomaterials (ENMs) have been developed for imaging, drug delivery, diagnosis, and clinical therapeutic purposes because of their outstanding physicochemical characteristics. However, the function and ultimate efficiency of nanomedicines remain unsatisfactory for clinical application, mainly because of our insufficient understanding of nanomaterial/nanomedicine-biology (nano-bio) interactions. The nonequilibrated, complex, and heterogeneous nature of the biological milieu inevitably influences the dynamic bioidentity of nanoformulations at each site (i.e., the interfaces at different biological fluids (biofluids), environments, or biological structures) of nano-bio interactions. The continuous interplay between a nanomedicine and the biological molecules and structures in the biological environments can, for example, affect cellular uptake or completely alter the designed function of the nanomedicine. Accordingly, the weak and strong driving forces at the nano-bio interface may elicit structural reconformation, decrease bioactivity, and induce dysfunction of the nanomaterial and/or redox reactions with biological molecules, all of which may elicit unintended and unexpected biological outcomes. In contrast, these driving forces also can be manipulated to mitigate the toxicity of ENMs or improve the targeting abilities of ENMs. Therefore, a comprehensive understanding of the underlying mechanisms of nano-bio interactions is paramount for the intelligent design of safe and effective nanomedicines. In this Account, we summarize our recent progress in probing the nano-bio interaction of nanomedicines, focusing on the driving force and redox reaction at the nano-bio interface, which have been recognized as the main factors that regulate the functions and toxicities of nanomedicines. First, we provide insight into the driving force that shapes the boundary of different nano-bio interfaces (including proteins, cell membranes, and biofluids), for instance, hydrophobic, electrostatic, hydrogen bond, molecular recognition, metal-coordinate, and stereoselective interactions that influence the different nano-bio interactions at each contact site in the biological environment. The physicochemical properties of both the nanoparticle and the biomolecule are varied, causing structure recombination, dysfunction, and bioactivity loss of proteins; correspondingly, the surface properties, biological functions, intracellular uptake pathways, and fate of ENMs are also influenced. Second, with the help of these driving forces, four kinds of redox interactions with reactive oxygen species (ROS), antioxidant, sorbate, and the prosthetic group of oxidoreductases are utilized to regulate the intracellular redox equilibrium and construct synergetic nanomedicines for combating bacteria and cancers. Three kinds of electron-transfer mechanisms are involved in designing nanomedicines, including direct electron injection, sorbate-mediated, and irradiation-induced processes. Finally, we discuss the factors that influence the nano-bio interactions and propose corresponding strategies to manipulate the nano-bio interactions for advancing nanomedicine design. We expect our efforts in understanding the nano-bio interaction and the future development of this field will bring nanomedicine to human use more quickly.

12.
Nano Lett ; 19(7): 4478-4489, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31244230

RESUMO

Silver nanoparticles (Ag NPs) have promising plasmonic properties, however, they are rarely used in biomedical applications because of their potent toxicity. Herein, an electron compensation effect from Au to Ag was applied to design safe Au@Ag core-shell NPs. The Ag shell thickness was precisely regulated to enable the most efficient electron enrichment in Ag shell of Au@Ag2.4 NPs, preventing Ag oxidation and subsequent Ag+ ion release. X-ray photoelectron spectroscopy and X-ray absorption near-edge structure analysis revealed the electron transfer process from Au core to Ag shell, and inductively coupled plasma optical emission spectroscopy analysis confirmed the low Ag+ ion release from Au@Ag2.4 NPs. Bare Au@Ag2.4 NPs showed much lower toxicological responses than Ag NPs in BEAS-2B and Raw 264.7 cells and acute lung inflammation mouse models, and PEGylation of Au@Ag2.4 NPs could further improve their safety to L02 and HEK293T cells as well as mice through intravenous injection. Further, diethylthiatri carbocyanine iodide attached pAu@Ag2.4 NPs exhibited intense surface-enhanced Raman scattering signals and were used for Raman imaging of MCF7 cells and Raman biosensing in MCF7 tumor-bearing mice. This electron compensation effect opens up new opportunity for broadening biomedical application of Ag-based NPs.

13.
Nano Lett ; 19(7): 4692-4701, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31244235

RESUMO

When a nanomedicine is administrated into the human body, biomolecules in biological fluids, particularly proteins, form a layer on the surface of the nanoparticle known as a "personalized protein corona". An understanding of the formation and behavior of the personalized protein corona not only benefits the nanotherapy treatment efficacy but also can aid in disease diagnosis. Here we used Gd@C82(OH)22 nanoparticles, a nanomedicine effective against several types of cancer, as a model nanomedicine to investigate the natural protein fingerprint of the personalized protein corona formed in 10 human lung squamous cell carcinoma patients. Our analysis revealed a specific biomarker, complement component C1q, in lung cancer personalized protein coronas, abundantly bound to Gd@C82(OH)22 NPs. This binding altered the secondary structure of C1q protein and led to the activation of an innate immune response, which could be exploited for cancer immune therapy. On the basis of this finding, we provide a new strategy for the development of precision nanomedicine derived from opsonization of a unique protein fingerprint within patients. This approach overcomes the common pitfall of protein corona formation and exploits the corona proteins to generate a precision nanomedicine and diagnostic tool.

14.
Adv Mater ; 31(33): e1901965, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237375

RESUMO

Antibacterial photocatalytic therapy has been reported as a promising alternative water disinfection technology for combating antibiotic-resistant bacteria. Numerous inorganic nanosystems have been developed as antibiotic replacements for bacterial infection treatment, but these are limited due to the toxicity risk of heavy metal species. Organic semiconductor photocatalytic materials have attracted great attention due to their good biocompatibility, chemically tunable electronic structure, diverse structural flexibility, suitable band gap, low cost, and the abundance of the resources they require. An all-organic composite photocatalytic nanomaterial C3 N4 /perylene-3,4,9,10-tetracarboxylic diimide (PDINH) heterostructure is created through recrystallization of PDINH on the surface of C3 N4 in situ, resulting in enhanced photocatalytic efficiency due to the formation of a basal heterostructure. The absorption spectrum of this composite structure can be extended from ultraviolet to near-infrared light (750 nm), enhancing the photocatalytic effect to produce more reactive oxygen species, which have an excellent inactivation effect on both Gram-negative and positive bacteria, while demonstrating negligible toxicity to normal tissue cells. An efficient promotion of infectious wound regeneration in mice with Staphylococcus aureus infected dermal wounds is demonstrated. This all-organic heterostructure shows great promise for use in wound disinfection.

15.
ACS Appl Mater Interfaces ; 11(26): 23093-23101, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31184853

RESUMO

Bacterial infections pose mounting public health concerns and cause an enormous medical and financial burden today. Rapid and sensitive detection of pathogenic bacteria at the point of care (POC) remains a paramount challenge. Here, we report a novel concept of bacteria-instructed click chemistry and employ it for POC microbial sensing. In this concept of bacteria-instructed click chemistry, we demonstrate for the first time that pathogenic bacteria can capture and reduce exogenous Cu2+ to Cu+ by leveraging their unique metabolic processes. The produced Cu+ subsequently acts as a catalyst to trigger the click reaction between gold nanoparticles (AuNPs) modified with azide and alkyne functional molecules, resulting in the aggregation of nanoparticles with a color change of the solution from red to blue. In this process, signal amplification from click chemistry is complied with the aggregation of functionalized AuNPs, thus presenting a robust colorimetric strategy for sensitive POC sensing of pathogenic bacteria. Notably, this colorimetric strategy is easily integrated in a smartphone app as a portable platform to achieve one-click detection in a mobile way. Moreover, with the help of the magnetic preseparation process, this smartphone app-assisted platform enables rapid (within 1 h) detection of Escherichia coli with high sensitivity (40 colony-forming units/mL) in the complex artificial sepsis blood samples, showing great potential for clinical early diagnosis of bacterial infections.

16.
Nat Nanotechnol ; 14(7): 719-727, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31235893

RESUMO

Anthropogenic carbon nanotubes, with a fibrous structure and physical properties similar to asbestos, have recently been found within human lung tissues. However, the reported carbon-nanotube-elicited pulmonary pathologies have been mostly confined to inflammatory or neoplastic lesions in the lungs or adjacent tissues. In the present study, we demonstrate that a single pulmonary exposure to multi-walled carbon nanotubes dramatically enhances angiogenesis and the invasiveness of orthotopically implanted mammary carcinoma, leading to metastasis and rapid colonization of the lungs and other organs. Exposure to multi-walled carbon nanotubes stimulates local and systemic inflammation, contributing to the formation of pre-metastatic and metastatic niches. Our study suggests that nanoscale-material-elicited pulmonary lesions may exert complex and extended influences on tumour progression. Given the increasing presence of carbon nanotubes in the environment, this report emphasizes the urgent need to escalate efforts assessing the long-term risks of airborne nanomaterial exposure in non-lung cancer progression.

17.
ACS Nano ; 13(6): 6801-6812, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31141658

RESUMO

Gadolinium-based contrast agents (GBCAs) are widely used for T1-weighted magnetic resonance imaging (MRI) in clinic diagnosis. However, a major drawback of GBCAs is that they can increase the toxicological risk of nephrogenic systemic fibrosis (NSF) in patients with advanced renal dysfunction. Hence, safer alternatives to GBCAs are currently in demand, especially for patients with renal diseases. Here we investigated the potential of polyethylene glycol (PEG)-stabilized iron oxide nanoclusters (IONCs) as biocompatible T1MRI contrast agents and systematically evaluated their NSF-related risk in rats with renal failure. We profiled the distribution, excretion, histopathological alterations, and fibrotic gene expressions after administration of IONCs and GBCAs. Our results showed that, compared with GBCAs, IONCs exhibited dramatically improved biosafety and a much lower risk of causing NSF, suggesting the feasibility of substituting GBCAs with IONCs in clinical MRI diagnosis of patients with renal diseases.

18.
J Gerontol Nurs ; 45(5): 39-45, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026331

RESUMO

The current study aimed to evaluate the multidimensional effects of an interdisciplinary care team in patients with Alzheimer's disease (AD). A total of 129 patients with AD were randomly assigned to an interdisciplinary care group (n = 69) or usual care group (n = 60). Behavioral and psychological symptoms of patients with AD were measured during a 6-month treatment period. No differences were found in the baseline characteristics between the interdisciplinary care and usual care groups. Compared to usual care, interdisciplinary care greatly increased patients' activities of daily living (ADL) scores when measured at 3 and 6 months (p < 0.001). Findings provide evidence that an interdisciplinary care team approach is beneficial in improving ADL performance; thus, an interdisciplinary care team should be implemented in the care arrangements for patients with AD. [Journal of Gerontological Nursing, 45(5), 39-45.].

19.
Adv Mater ; 31(19): e1808303, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30883982

RESUMO

Advances in the field of nanotechnology together with an increase understanding of tumor immunology have paved the way for the development of more personalized cancer immuno-nanomedicines. Nanovehicles, due to their specific physicochemical properties, are emerging as key translational moieties in tackling tumor-promoting, M2-like tumor-associated macrophages (TAMs). Cancer immuno-nanomedicines target TAMs primarily by blocking M2-like TAM survival or affecting their signaling cascades, restricting macrophage recruitment to tumors and re-educating tumor-promoting M2-like TAMs to the tumoricidal, M1-like phenotype. Here, the TAM effector mechanisms and strategies for targeting TAMs are summarized, followed by a focus on the mechanistic considerations in the development of novel immuno-nanomedicines. Furthermore, imaging TAMs with nanoparticles so as to forecast a patient's clinical outcome, describing treatment options, and observing therapy responses is also discussed. At present, strategies that target TAMs are being investigated not only at the basic research level but also in early clinical trials. The significance of TAM-targeting biomaterials is highlighted, with the goal of facilitating future clinical translation.

20.
Chemosphere ; 223: 263-274, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784734

RESUMO

Particulate matter (PM) exposure poses many adverse effects on human health. However, it is challenging to clearly differentiate between the contributions of individual pollutants on toxicity from complex mixtures of ambient air pollutants. The aim of this study is to generate aerosols constituted by silica nanoparticles (NPs) and bisulfate to serve as simulators of particle-associated high-sulfur air pollution. Then, the health impacts of sulfur dioxide were evaluated at the cellular level using an air-liquid interface (ALI) exposure chamber. BEAS-2B cells were exposed to either nano-silica or bisulfite aerosol individually or bisulfate-coated silica (SiO2-NH2@HSO3) for 3 h using the ALI. The cellular toxicities were carefully compared based on the exposure dosages. The ALI exposure of SiO2 NPs alone did not produce any apparent cytotoxicity in cells, but the aerosol exposure of SiO2-NH2@HSO3 significantly decreased the cell viability and enhanced the production of cellular reactive oxygen species in a dose-dependent manner. Consequently, the excessive oxidative stress resulted in mitochondrial damage as well as cellular apoptosis. ALI exposure can possibly reflect the realistic physiological exposure condition of the human respiratory system. As a derivative of the sulfur dioxide component of air pollution, sulfate exacerbates the toxic effects of inhalable PMs. This result may be due to the large surface area of the nanoparticles, with the possibility of carrying more sulfite to the target cells during aerosol exposure. The sulfate levels offer a meaningful complement to the present PM2.5 index of air pollution for achieving better human health protection.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/análise , Modelos Biológicos , Material Particulado/efeitos adversos , Aerossóis , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Medição de Risco , Dióxido de Silício/efeitos adversos , Sulfatos/efeitos adversos
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