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1.
J Nanobiotechnology ; 17(1): 83, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291948

RESUMO

BACKGROUND: Macrophages with tumor-tropic migratory properties can serve as a cellular carrier to enhance the efficacy of anti neoplastic agents. However, limited drug loading (DL) and insufficient drug release at the tumor site remain the main obstacles in developing macrophage-based delivery systems. In this study, we constructed a biomimetic delivery system (BDS) by loading doxorubicin (DOX)-loaded reduced graphene oxide (rGO) into a mouse macrophage-like cell line (RAW264.7), hoping that the newly constructed BDS could perfectly combine the tumor-tropic ability of macrophages and the photothermal property of rGO. RESULTS: At the same DOX concentration, the macrophages could absorb more DOX/PEG-BPEI-rGO than free DOX. The tumor-tropic capacity of RAW264.7 cells towards RM-1 mouse prostate cancer cells did not undergo significant change after drug loading in vitro and in vivo. PEG-BPEI-rGO encapsulated in the macrophages could effectively convert the absorbed near-infrared light into heat energy, causing rapid release of DOX. The BDS showed excellent anti-tumor efficacy in vivo. CONCLUSIONS: The BDS that we developed in this study had the following characteristic features: active targeting of tumor cells, stimuli-release triggered by near-infrared laser (NIR), and effective combination of chemotherapy and photothermotherapy. Using the photothermal effect produced by PEG-BPEI-rGO and DOX released from the macrophages upon NIR irradiation, MAs-DOX/PEG-BPEI-rGO exhibited a significant inhibitory effect on tumor growth.


Assuntos
Antineoplásicos/química , Materiais Biomiméticos/química , Portadores de Fármacos/química , Macrófagos/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Liberação Controlada de Fármacos , Grafite/química , Humanos , Hipertermia Induzida , Raios Infravermelhos , Lasers , Masculino , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Polietilenoimina/química , Distribuição Tecidual
2.
Int J Nanomedicine ; 14: 4367-4381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354266

RESUMO

Purpose: Polyethylenimine (PEI) has been widely used as a versatile template to develop multifunctional nanosystems for disease diagnosis and treatment. In this study, we manufactured iodine-131 (131I)-labeled PEI-entrapped gold nanoparticles (Au PENPs) as a novel nanoprobe for single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and radionuclide therapy. Materials and methods: PEI was PEGylated and sequentially conjugated with Buthus martensii Karsch chlorotoxin (BmK CT, a tumor-specific ligand which can selectively bind to MMP2), 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate to form the multifunctional PEI template for entrapment of Au NPs. Then, the PEI surface was radiolabeled with 131I via HPAO to produce the novel nanoprobe (BmK CT-Au PENPs-131I). Results: The synthesized multifunctional Au PENPs before and after 131I radiolabeling were well-characterized as follows: structure, X-ray attenuation coefficient, colloid stability, cytocompatibility, and radiochemical stability in vitro. Furthermore, BmK CT-Au PENPs-131I were suitable for targeted SPECT/CT imaging and radionuclide therapy of tumor cells in vitro and in a xenograft tumor model in vivo. Conclusion: The developed multifunctional Au PENPs are a promising theranostic platform for targeted imaging and treatment of different MMP2-overexpressing tumors.


Assuntos
Ouro/química , Radioisótopos do Iodo/química , Nanopartículas Metálicas/química , Polietilenoimina/química , Compostos Radiofarmacêuticos/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Coloides/química , Glioma/patologia , Glioma/radioterapia , Humanos , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Nus , Especificidade de Órgãos , Tamanho da Partícula , Propionatos/química , Venenos de Escorpião/toxicidade
3.
Life Sci ; 232: 116661, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31323272

RESUMO

AIMS: The development of highly efficient and low toxic non-viral gene delivery vectors is the most challenging issues for successful application of gene therapy. A particular focus has been on understanding structure-activity relationships for transfection activity and toxicity of polyethylenimine (PEI). During the last decade, the use of cerium oxide nanoparticles (CeO2-NPs) in biomedicine has attracted much attention due to their pH-dependent antioxidant activity. CeO2-NPs provide protection normal cells from various forms of reactive oxygen species, but possess innate cytotoxicity and apoptosis to cancer cells. The purpose of this study was to design a new class of gene carriers by low molecular weight PEI (B-PEI 10 kDa) coordination onto CeO2-NPs. MAIN METHODS: B-PEI 10 kDa was conjugated to CeO2-NPs by Epichlorohydrin linker. Transfection efficiency, cytotoxic and apoptotic effects of pDNA-PEI-CeO2 NPs were evaluated on WEHI 164 cancer cells and normal L929 cells lines. KEY FINDINGS: PEI-CeO2 NPs was able to condense the pDNA at carrier/plasmid (C/P) weight ratios of 0.5. The size and zeta potential of pDNA-PEI-CeO2 NPs were 124 ±â€¯7 nm and 22 ±â€¯2 mV, respectively. The transfection efficacy of synthesized pDNA-PEI-CeO2 NPs improved and the cytotoxicity was decreased compared to pDNA-PEI. Moreover, pDNA-PEI-CeO2 NPs induced more apoptosis than unmodified PEI and CeO2-NPs control groups. pDNA-PEI-CeO2 NPs displayed more transfection, cytotoxicity, and apoptosis in WEHI 164 cancer cells than normal L929 cells. SIGNIFICANCE: In conclusion, PEI-CeO2 nanocarriers could act as a potential candidate for gene and drug delivery to cancerous and tumor cells.


Assuntos
Cério/química , Vetores Genéticos , Nanopartículas Metálicas/química , Polietilenoimina/química , Transfecção , Animais , Linhagem Celular , Linhagem Celular Tumoral , DNA/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Plasmídeos , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Food Chem ; 293: 197-203, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151601

RESUMO

The purpose of this research was to prepare nanogels by covalent cross-linking carboxymethyl starch (CMS) and chitosan hydrochloride (CHC) as novel delivery systems for curcumin. The spherical structure of CHC-CMS nanogels was verified by transmission electron microscopy. Fourier transform infrared spectroscopy confirmed that the amide linkage was formed between CHC and CMS. X-ray diffraction data exhibited that the crystalline structure of CHC was destroyed after covalent cross-linking with CMS, which further confirmed that the CHC-CMS nanogels were formed. Furthermore, the nanogels behaved as viscoelastic solids over the entire frequency range. Meanwhile, the nanogels showed excellent pH-sensitivity and high encapsulation efficiency of curcumin (89.49%-94.01%). Compared to free curcumin, curcumin encapsulated in nanogels displayed sustained release profile in simulated gastrointestinal conditions. These results suggested that the nanogels had been successfully fabricated and could be used as ideal carriers for curcumin and other bioactive compounds in functional foods.


Assuntos
Quitosana/química , Curcumina/química , Portadores de Fármacos/química , Polietilenoglicóis/química , Polietilenoimina/química , Amido/análogos & derivados , Curcumina/metabolismo , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Reologia , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/química , Difração de Raios X
5.
Int J Nanomedicine ; 14: 3361-3373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190797

RESUMO

Purpose: To fabricate multifunctional nanocapsule via Pickering emulsion route to facilitate tumor-targeted delivery. Methods: Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles (PNA) stabilized nanocapsules were fabricated by Pickering emulsion (PE) technology. For controllable drug-release and enhancing targeted antitumor effects, the nanocapsules were crosslinked with cystamine and coupled on cell-surface molecule markers (cRGDfK) to achieve on-demand drug release and targeted delivery. Results: The fabricated PE and nanocapsules with average particle sizes (250 and 150 nm) were obtained. Encapsulation efficiency of hydrophobic anticancer drug (DOX) was determined as >90%. Release kinetic profiles for encapsulated nanocapsules displayed circulation stability and redox-sensitive releasing behavior with the supposed increase bioavailability. Both cytotoxicity assay, cellular uptake analysis and anticancer efficacy in B16F10 murine model demonstrated these redox-responsive drug-release and active targeted delivery. Conclusion: The results clearly demonstrated nanocapsule via PE route as promising candidate to provide an effective platform for incorporating hydrophobic drug for targeted cancer chemotherapy.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Nanocápsulas/química , Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/química , Resinas Acrílicas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular , Reagentes para Ligações Cruzadas/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanocápsulas/ultraestrutura , Oxirredução , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoimina/química
6.
J Photochem Photobiol B ; 197: 111532, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31212245

RESUMO

Glutathione (GSH) plays critical roles in many physiological processes usually present in live cells, and altered levels have been linked to some clinical pathological conditions. However, current techniques of GSH detection with fluorescence assay strategies remain poorly researched. In this work, branched polyethylenimine-functionalized carbon dots (PEI-CDs) are synthesized by simple hydrothermal treatment of glucose and PEI. The fluorescence of the PEI-CDs could be efficiently quenched by Cu2+ and then recovered by some biothiols. Basing on this, a "turn-on" fluorescent probe for detecting GSH has been developed using PEI-CDs-Cu2+ system. Compared with traditional probes for GSH detection, a significant advantage of the PEI-CDs-Cu2+ system is that it can be used for GSH detection at both low and high concentrations with different concentration combinations of PEI-CDs and Cu2+. More specifically, two good linear relationships are achieved in the ranges of 0-80 µM and 0-1400 µM for GSH, respectively. Correspondingly, the detection limits of GSH are 0.33 µM and 9.49 µM, respectively. The quantum yields (QYs) of PEI-CDs and PEI-CDs-Cu2++GSH was 9.6% and 4.2%, respectively. Moreover, the PEI-CDs-Cu2+ has excellent optical stability and good biocompatibility. Additionally, it is worth noting that the developed probe has successfully realized the visualization of GSH detection in MGC-803 cells.


Assuntos
Cobre/química , Corantes Fluorescentes/química , Glutationa/análise , Polietilenoimina/química , Pontos Quânticos/química , Espectrometria de Fluorescência/métodos , Carbono/química , Linhagem Celular Tumoral , Humanos , Limite de Detecção , Microscopia Confocal , Neoplasias Gástricas/patologia
7.
Food Chem ; 293: 340-347, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151621

RESUMO

A green and simple method was designed to synthesize polyethyleneimine (PEI)-modified magnetic nanoparticles (MNPs), which were later used as adsorbents in magnetic solid phase extraction (MSPE) process. A new MSPE-HPLC method was then established for the simultaneous determination of four representative synthetic colorants (Amaranth, Ponceau 4R, Sunset yellow and Allure red) in food samples. Several important factors, such as the pH of the sample solution, the amount of adsorbent, the adsorption time, and the type of the eluent were investigated in detail. Under the optimized experimental conditions, the four colorants were measured with good linearity, detection limit and quantification limit. Adsorption kinetics and isotherms were also investigated to elucidate the adsorption mechanism. The detection of four colorants in candy, jelly and carbonated drink proved that the established MSPE-HPLC method was simple and effective and can be used for the analysis of colorants in real samples.


Assuntos
Bebidas/análise , Análise de Alimentos/métodos , Corantes de Alimentos/análise , Nanopartículas de Magnetita/química , Polietilenoimina/química , Adsorção , Compostos Azo/análise , Doces/análise , Cromatografia Líquida de Alta Pressão , Química Verde , Concentração de Íons de Hidrogênio , Limite de Detecção , Naftalenossulfonatos/análise , Reprodutibilidade dos Testes , Extração em Fase Sólida/instrumentação , Extração em Fase Sólida/métodos
8.
AAPS PharmSciTech ; 20(5): 213, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165298

RESUMO

Thermo and pH-responsive poly-N-isopropylacrylamide (PNIPAM) polymer has gained interest due to microenvironment targeting potential toward cancer cells. Its exceptional potential of the phase transition at body temperature (37°C) makes it biologically relevant for drug delivery and biosensing. The optimum drug loading and particle size with controlled release at a specific site are essential for critical process parameters (CPP). This study investigates the formulation optimization anastrozole (ANST)-loaded PNIPAM nanoparticle (NPs) prepared by solvent evaporation method for pH- and thermo-responsive drug delivery. Box-Behnken design (BBD) was implemented to observe the effect of selected process parameters on quality attributes product including particle size 110.15 nm, zeta potential - 11.02 mV, PDI 0.175, and drug loading 8.35% (DL). The statistical data was found to fit in the quadratic model and p value is less than 0.005. The thermo-responsive behavior of PNIPAM is evaluated on DLS and UV-Visible spectroscopy at elevated temperature to 60°C that has shown increment in turbidity showed aggregation of the nanoparticles. The TEM and AFM revealed the spherical and smooth surface ANST-PNIPAM NPs. The formulation showed the controlled release of ANST for 48 h at pH 7.4 and triggered release at simulated tumor microenvironment pH 5.0. The in vitro cytotoxicity of the formulation is higher than free ANST and shown dose-dependent cell viability. The higher cell uptake was observed by NPs after 12-h incubation in MCF-7 cell lines using confocal microscopy. Apoptotic evaluation of ANST-PNIPAM NPs exhibited 22.67% in comparison to free ANST where 6% was analyzed on the flow cytometer.


Assuntos
Resinas Acrílicas/química , Anastrozol/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Concentração de Íons de Hidrogênio , Nanoestruturas/química , Temperatura Ambiente , Sistemas de Liberação de Medicamentos/métodos , Géis , Humanos , Células MCF-7 , Transição de Fase , Polietilenoimina/química
9.
J Biomed Nanotechnol ; 15(7): 1454-1467, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196350

RESUMO

CpG ODN acts as a 'pathogen-associated' molecular pattern that is recognized by intracellular Toll-like receptor 9 and can induce a robust dendritic cells (DCs) activation to against various diseases. However, the CpG ODN is restricted with critical defects of easily enzymolysis and negligible phagocytosis. To overcome these issues, a simpler and competent nanocarrier of mannose modified PEGylated branched PEI25k (PEI-PEG-Man) was designed to achieve excellent DCsspecific delivery of CpG. Nanoparticles of PEI-PEG-Man encapsulating CpG (PEI-PEG-Man@CpG) possessed elevated gene loading capacity, biological stability and admirable anti-enzymolysis ability. PEI-PEG-Man@CpG could be selectively uptake by DCs through a receptor-mediated endocytosis, which generates a potent immunostimulatory activity on bone marrow derived dendritic cells (BMDCs) evidenced by significantly upregulation of the pro and anti-inflammatory cytokines (TNF-α, IL-6) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) on BMDCs in vitro. More importantly, the results of in vivo targeting assay showed that PEI-PEG-Man@CpG nanoparticles could remarkably boost CpG accumulation in lymph lodes upon subcutaneous administration in C57BL/6 mice, which facilitated maturation of DCs and productions of anti-inflammatory cytokines. Our results suggested that PEI-PEG-Man@CpG nanoparticles, in the future, might function as a powerful vector for ex vivo engineering to promote DC targeting and maturation, which enhance vaccine efficiency against cancer or infectious disease.


Assuntos
Polietilenoimina/química , Animais , Células Dendríticas , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas , Oligodesoxirribonucleotídeos
10.
Anal Chim Acta ; 1070: 80-87, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31103170

RESUMO

The ultrasensitive bioassays are increasingly demanded for disease diagnosis and environmental monitoring. The combined unique natures of the components in nanocomposites have led to their wide applications in bioanalysis. In the current study, a simple strategy for preparing polyethyleneimine-functionalized reduced graphene oxide-hemin-bovine serum albumin (PEI-rGO-Hemin-BSA) nanocomposites as peroxidase mimetics was demonstrated. The developed nanocomposites of PEI-rGO-Hemin-BSA showed an excellent peroxidase-like activity. Importantly, through the glutaradelhyde crosslinking, PEI-rGO-Hemin-BSA could be further simply combined with various oxidases such as glucose oxidase, cholesterol oxidase, lactate oxidase and choline oxidase for the detection and quantitative measurement of multiple metabolites including glucose, cholesterol, l-lactate, and choline. The developed detection strategy, which is sensitive, convenient, low-costed, and in tiny sample consumption, could be expected wide applications in the disease diagnosis and management of metabolite disorders.


Assuntos
Grafite/química , Hemina/química , Doenças Metabólicas/diagnóstico , Nanocompostos/química , Peroxidase/metabolismo , Polietilenoimina/química , Soroalbumina Bovina/química , Animais , Bovinos , Colesterol/análise , Colesterol/metabolismo , Colina/análise , Colina/metabolismo , Glucose/análise , Glucose/metabolismo , Humanos , Ácido Láctico/análise , Ácido Láctico/metabolismo , Oxirredução
11.
Anal Bioanal Chem ; 411(14): 3081-3089, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31076818

RESUMO

In this work, a facile and label-free ratiometric sensor is constructed for selective determination of norepinephrine (NE) by coupling second-order scattering (SOS) and fluorescence, two different and independent optical signals. Herein, polyethyleneimine (PEI) dilute solution medium shows an intensive SOS signal without any fluorescence response. Interestingly, NE can be selectively induced by PEI to emit bright fluorescence, and meanwhile causes an observable decrease in the SOS signal due to the interactions between NE and PEI. The simultaneous variation of the two independent signals can be used for ratiometric sensing of NE. Under the optimal conditions, the resultant ratiometric sensor displays high sensitivity and selectivity toward NE by simultaneously monitoring fluorescence and SOS signals with the same excitation wavelength. The proposed sensor exhibits a good linear relationship versus NE concentration in the range of 10.0 nM-45.0 µM with a detection limit of 2.0 nM (S/N = 3) and has been successfully applied to the determination of NE in real samples without the use of any extra reagent. The combination of fluorescence and SOS signals provides a new scheme for ratiometric sensor design, greatly simplifying experimental procedure and effectively enhancing detection accuracy. Moreover, the proposed analytical strategy further broadens the application of dilute solutions of polymers in research into optical sensor and green analytical chemistry. Graphical abstract.


Assuntos
Norepinefrina/análise , Óptica e Fotônica/instrumentação , Espalhamento de Radiação , Espectrometria de Fluorescência/métodos , Estudos de Viabilidade , Fluorescência , Luz , Limite de Detecção , Norepinefrina/normas , Norepinefrina/urina , Tamanho da Partícula , Polietilenoimina/química , Portulaca/química , Padrões de Referência
12.
Int J Nanomedicine ; 14: 2655-2665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118606

RESUMO

Background: Carbon dots (CDots) have recently been demonstrated their effective visible light-activated antimicrobial activities toward bacteria. This study was to evaluate and understand the roles of the surface functionalities in governing the antimicrobial activity of CDots. Methods: Using the laboratory model bacteria Bacillus subtilis, the photo-activated antimicrobial activities of three groups of CDots with specifically selected different surface functionalization moieties were evaluated and compared. The first group consisting of CDots with surface functionalization by 2,2-(ethylenedioxy)bis(ethylamine) (EDA) vs. 3-ethoxypropylamine (EPA), was evaluated to determine the effect of different terminal groups/charges on their photo-activated antibacterial activities. The second group consisting of CDots functionalized with oligomeric polyethylenimine (PEI) and those prepared by the carbonization of PEI - citric acid mixture, was to evaluate the effects of dot surface charges vs. fluorescent quantum yields on their antimicrobial activities. The third group consisting of CDots functionalized with PEI of 1,200 vs. 600 in average molecular weight was evaluated for the effect of molecular weight of surface passivation molecular on their antimicrobial activities. Results: The results indicated the EDA-CDots in the first group was more effective and was attributed to the positive charges from the protonation of the amino groups (-NH2) being more favorable to interactions with bacterial cells. The evaluation of the second group CDots suggested the same surface charge effect dominating the antibacterial performance over the fluorescent quantum yields. The evaluation of the third group CDots functionalized with PEI of 1,200 vs. 600 in average molecular weight, indicated the latter was significantly more effective. Conclusions: The results from this study highlighted the dominant role of surface functionalities in governing CDots' light activated antimicrobial activity and should have significant implications to the further design and development of CDots as a new class of visible light-activated antibacterial agents.


Assuntos
Antibacterianos/farmacologia , Carbono/farmacologia , Luz , Bacillus subtilis/efeitos dos fármacos , Etilaminas/química , Testes de Sensibilidade Microbiana , Polietilenoimina/química , Propilaminas/química , Propriedades de Superfície
13.
Int J Nanomedicine ; 14: 2973-2983, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118616

RESUMO

Objective: Intraocular pressure has always been a great challenge for topical ophthalmic drugs. The study aimed to develop ocular surfactant based nanovesicles (NVs) carried in mucoadhesive nanogel providing efficient topical delivery of acetazolamide (ACZ). Methods: For the sake of optimizing formulation parameters, the effect of the type of edge activator and its ratio to sorbitan monostearate (Span 60) on the mean particle size, entrapment efficiency (%EE), and zeta potential (ZP) of produced NVs was investigated. Results: The selected formulation composed of Span 60:sodium deoxycholate with ratio 80:20 showed an average diameter of 202.90 nm, %EE of 90.2%, and ZP of -38.1 mV with a spherical and smooth surface. The ACZ loaded nanovesicles (ACZ-NVs) were embedded in different concentrations of Chitosan-sodium tripolyphosphate (CS-TPP) nanogels. The nanogel prepared using 1.5% CS showed the most promising viscosity, adhesion time, and rheological behavior (118,246 cP, 290 min, and thixotropic behavior, respectively). The in vitro release of ACZ showed a controlled release profile after incorporation in nanogels. The in vivo irritation test showed minimal irritation for the nanogel formulation compared to ACZ topical suspension. The effect of intraocular pressure lowering was significantly prolonged using ACZ-NV nanogels compared to ACZ oral tablets. Histopathological examination emphasized the healing power of CS on retinal atrophy. Conclusion: The research work indicated a promising potential for successful topical delivery of ACZ.


Assuntos
Acetazolamida/administração & dosagem , Acetazolamida/farmacologia , Sistemas de Liberação de Medicamentos , Olho/efeitos dos fármacos , Nanopartículas/química , Polietilenoglicóis/química , Polietilenoimina/química , Tensoativos/química , Animais , Liberação Controlada de Fármacos , Hexoses/química , Pressão Intraocular/efeitos dos fármacos , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Coelhos
14.
Int J Nanomedicine ; 14: 3189-3201, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118631

RESUMO

Purpose: Early diagnosis is essential for reducing liver cancer mortality, and molecular diagnosis by magnetic resonance imaging (MRI) is an emerging and promising technology. The chief aim of the present work is to use the ferritin gene, modified by the alpha-fetoprotein (AFP) promoter, carried by a highly safe vector, to produce signal contrast on T2-weighted MR imaging as an endogenous contrast agent, and to provide a highly specific target for subsequent therapy. Methods: Polyethyleneimine-ß-cyclodextrin (PEI-ß-CD, PC) was synthesized as a novel vector. The optimal nitrogen/phosphorus ratio (N/P) of the PC/plasmid DNA complex was determined by gel retardation, biophysical properties and transmission electron microscopy morphological analysis. The transfection efficiency was observed under a fluorescence microscope and analyzed by flow cytometry. Cellular iron accumulation caused by ferritin overexpression was verified by Prussian blue staining, and the resulting contrast imaging effect was examined by MRI. Results: The modified cationic polymer PC was much safer than high molecular weight PEI, and could condense plasmid DNA at an N/P ratio of 50 with suitable biophysical properties and a high transfection efficiency. Overexpression of ferritin enriched intracellular iron. The short-term iron imbalance initiated by AFP promoter regulation only occurred in hepatoma cells, resulting in signal contrast on MRI. The specific target TfR was also upregulated during this process. Conclusion: These results illustrate that the regulated ferritin gene carried by PC can be used as an endogenous contrast agent for MRI detection of hepatocellular carcinoma (HCC). This molecular imaging technique may promote safer early diagnosis of HCC, and provide a more highly specific target for future chemotherapy drugs.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Ferritinas/genética , Neoplasias Hepáticas/diagnóstico por imagem , Imagem por Ressonância Magnética , Imagem Molecular/métodos , Poliaminas/química , Carcinoma Hepatocelular/patologia , Morte Celular , Linhagem Celular Tumoral , DNA/metabolismo , Células HEK293 , Humanos , Ferro/metabolismo , Neoplasias Hepáticas/patologia , Tamanho da Partícula , Plasmídeos/metabolismo , Polietilenoimina/química , Regiões Promotoras Genéticas , Espectroscopia de Prótons por Ressonância Magnética , Receptores da Transferrina/metabolismo , Eletricidade Estática
15.
Int J Nanomedicine ; 14: 3221-3234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123399

RESUMO

Background: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and surface modified PLGA nanoparticles have been widely studied as antigens or drugs carriers due to their controlled release characteristics and biocompatibility. However, most PLGA nanoparticles have lower antigens loading efficiency and adjuvanticity. Purpose: The aim of this study was to improve the antigen loading efficiency and adjuvant activity of PLGA nanoparticles. Materials and methods: Surface cationic polymer modification can improve the antigens loading efficiency of PLGA nanoparticles by surface adsorption. Therefore, in this study, chitosan modified PLGA nanoparticles (CS-AHPP/OVA), polyethyleneimine modified PLGA nanoparticles (PEI-AHPP/OVA), and ε-Poly-L-lysine modified PLGA nanoparticles (εPL-AHPP/OVA) were prepared as antigen delivery carriers to investigate the characterization and stability of these nanoparticles. These nanoparticles were evaluated for their efficacies as adjuvants pre- and post-modification. Results: The AHP and OVA-loaded PLGA nanoparticles (AHPP/OVA) were positively charged after surface cationic polymers modification, and their structural integrity was maintained. Their antigen loading capacity and stability of nanoparticles were improved by the surface cationic polymers modification. Increased positive surface charge resulted in greater OVA adsorption capacity. Among AHPP/OVA and the three surface cationic polymers synthesized from modified PLGA nanoparticles, PEI-AHPP/OVA showed the highest antigen loading efficiency and good stability. AHPP/OVA, CS-AHPP/OVA PEI-AHPP/OVA, and εPL-AHPP/OVA formulations significantly enhanced lymphocyte proliferation and improved the ratio of CD4+/CD8+ T cells. In addition, AHPP/OVA, PEI-AHPP/OVA and εPL-AHPP/OVA formulations induced secretion of cytokines (TNF-α, IFN-γ, IL-4, and IL-6), antibodies (IgG) and antibody subtypes (IgG1 and IgG2a) in immunized mice. These results demonstrate that these formulations generated a strong Th1-biased immune response. Among them, PEI-AHPP/OVA induced the strongest Th1-biased immune response. Conclusion: In conclusion, PEI-AHPP/OVA nanoparticles may be a potential antigen delivery system for the induction of strong immune responses.


Assuntos
Sistemas de Liberação de Medicamentos , Mel , Imunidade Celular , Ovalbumina/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/química , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Formação de Anticorpos , Antígenos/metabolismo , Cátions , Proliferação de Células , Quitosana/química , Citocinas/sangue , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Ativação Linfocitária , Camundongos Endogâmicos ICR , Nanopartículas/química , Ovalbumina/imunologia , Polietilenoimina/química , Baço/citologia , Linfócitos T/imunologia , Vacinação , Vacinas/imunologia
16.
Nanoscale ; 11(18): 9163-9175, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31038150

RESUMO

Diabetes is a chronic metabolic disorder disease characterized by high blood glucose levels and has become one of the most serious threats to human health. In recent decades, a number of insulin delivery systems, including bulk gels, nanogels, and polymeric micelles, have been developed for the treatment of diabetes. Herein, a kind of glucose and H2O2 dual-responsive polymeric nanogel was designed for enhanced glucose-responsive insulin delivery. The polymeric nanogels composed of poly(ethylene glycol) and poly(cyclic phenylboronic ester) (glucose and H2O2 dual-sensitive groups) were synthesized by a one-pot thiol-ene click chemistry approach. The nanogels displayed glucose-responsive release of insulin and the release rate could be promoted by the incorporation of glucose oxidase (GOx), which generated H2O2 at high glucose levels and H2O2 further oxidizes and hydrolyzes the phenylboronic ester group. The nanogels have characteristics of long blood circulation time, a fast response to glucose, and excellent biocompatibility. Moreover, subcutaneous delivery of insulin to diabetic mice with the insulin/GOx-loaded nanogels presented an effective hypoglycemic effect compared to that of injection of insulin or insulin-loaded nanogels. This kind of nanogel would be a promising candidate for the delivery of insulin in the future.


Assuntos
Glucose Oxidase/química , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Hipoglicemiantes/metabolismo , Insulina/metabolismo , Polietilenoglicóis/química , Polietilenoimina/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Química Click , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Glucose/química , Glucose Oxidase/metabolismo , Teste de Tolerância a Glucose , Peróxido de Hidrogênio/química , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Insulina/química , Insulina/uso terapêutico , Camundongos , Células NIH 3T3 , Polietilenoglicóis/toxicidade , Polietilenoimina/toxicidade
17.
Food Chem ; 294: 468-476, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31126489

RESUMO

Detection of pathogenic bacteria by polymerase chain reaction (PCR) is progressively emerging, although it is still hindered by a complex matrix, long-term bacterial enrichment and low bacterial abundance. Here, we report a novel material based on boronate affinity for recognition and enrichment of bacteria using a pre-PCR method. After optimization, the material exhibited high boronate affinity toward bacteria, with adsorption capacities of S. aureus and Salmonella spp. incubated in 0.01 M PBS (pH 7.4) at 37 °C for 15 min calculated as (906.60 ±â€¯15.73) × 107 cfu/g and (582.59 ±â€¯13.19) × 107 cfu/g, respectively, without any bacterial death during the binding process. The material was then applied to enrich S. aureus and Salmonella spp. from the spiked water and 25% cow milk samples followed by mPCR, which resulted in high bacterial enrichment and demonstrated great potential for selective enrichment of bacteria in food samples.


Assuntos
Compostos de Boro/química , Microbiologia de Alimentos/métodos , Salmonella/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Adsorção , Animais , Compostos de Boro/síntese química , Bovinos , Água Potável/microbiologia , Doenças Transmitidas por Alimentos/microbiologia , Concentração de Íons de Hidrogênio , Leite/microbiologia , Polietilenoimina/química , Reação em Cadeia da Polimerase , Salmonella/genética , Sensibilidade e Especificidade , Sefarose/química , Staphylococcus aureus/genética
18.
Chemosphere ; 229: 570-579, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100628

RESUMO

Trace anionic dyes in wastewater are difficult to be rapidly and efficiently removed because they are completely soluble and poorly biodegradable. Herein, a facile and environmentally friendly adsorbent was fabricated via the surface functioned SiO2 with abundant amine groups of polyethyleneimine (PEI). The structural characterization indicated that PEI was successfully immobilized on the SiO2 surface. The adsorption performance of SiO2-PEI was evaluated using acid orange II (AOII) as model pollutant. The adsorption of AOII on SiO2-PEI displayed high removal rates in the pH range of 2.0-9.0, and exhibited ultrafast removal (99.1% removal rate at 10 min). The adsorption behavior fitted well with the Langmuir isotherm and pseudo-second-order kinetic model, and the maximum uptake capability of AOII was higher than 705.3 mg/g. The excellent adsorption capacity of AOII on SiO2-PEI mainly relied on the electrostatic attraction between the sulfonic acid group of AOII and amine group of PEI in the adsorption process. Additionally, other anionic dyes like acid fuchsin and direct sky blue 5B could also be fast and efficiently removed by SiO2-PEI. This work is expected to open new possibilities for the ultrafast removal of anionic dye pollutants.


Assuntos
Compostos Azo/isolamento & purificação , Corantes/isolamento & purificação , Nanopartículas/química , Naftalenos/isolamento & purificação , Polietilenoimina/química , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Ânions , Compostos Azo/química , Benzenossulfonatos/química , Benzenossulfonatos/isolamento & purificação , Corantes/química , Cinética , Microscopia Eletrônica de Varredura , Naftalenos/química , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Eliminação de Resíduos Líquidos/instrumentação , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/química , Difração de Raios X
19.
Biosens Bioelectron ; 138: 111311, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31103930

RESUMO

A novel electrochemical sensor with inherent redox activity mediated by ferrocene for Cystatin C (CysC), an early kidney failure biomarker, is described. The current response was mediated by graphene oxide-ferrocene nanofilm with redox-activity coming from electroactive species surface-confined. Anti-CysC antibodies were immobilized by their Fc portions on the drop-casting polyethyleneimine (PEI) film for improving the sensitivity and reproducibility. Stepwise modifications of the nanostructured surface were characterized by electrochemical techniques, FT-IR and AFM. FT-IR confirmed the formation of the Fc-GO nanocomposite and PEI deposition on the electrode surface. The AFM micrographs confirmed a nanometric film of Fc-GO and PEI. The sensor platform showed a response from 0.1 to 1000 ng/mL and lower limit of detection (LOD) of 0.03 ng/mL of CysC, with good accuracy, specificity and it was successfully applied for CysC detection. Advantages of this immunosensor include rapid testing with minimal steps by the simple use of an intrinsic redox probe, working in a reduction potential, which avoids potential interferences. This proposal attempts to circumvent amperometric detection limitations and provides a promising candidate for future point-of-care diagnostics without redox probe additional solutions for measurements.


Assuntos
Cistatina C/análise , Compostos Ferrosos/química , Grafite/química , Metalocenos/química , Nanocompostos/química , Biomarcadores/análise , Técnicas Biossensoriais , Técnicas Eletroquímicas , Imunoensaio , Limite de Detecção , Oxirredução , Polietilenoimina/química , Sensibilidade e Especificidade
20.
Artigo em Inglês | MEDLINE | ID: mdl-30940556

RESUMO

Toxicity of AgNPs has been widely studied in waterborne exposed aquatic organisms. However, toxic effects caused by AgNPs ingested through the diet and depending on the season are still unexplored. The first cell response after exposure to xenobiotics occurs at gene transcription level. Thus, the aim of this study was to assess transcription level effects in the digestive gland of female mussels after dietary exposure to AgNPs both in autumn and in spring. Mussels were fed daily for 21 days with Isochrysis galbana microalgae previously exposed for 24 h to a dose close to environmentally relevant concentrations of 1 µg Ag/L PVP/PEI coated 5 nm AgNPs (in spring) and to a higher dose of 10 µg Ag/L of the same AgNPs both in autumn and in spring. After 1 and 21 days, mussels RNA was hybridized in a custom microarray containing 7806 annotated genes. Mussels were more responsive to the high dose compared to the low dose of AgNPs and a higher number of probes were altered in autumn than in spring. In both seasons, significantly regulated genes were involved in the cytoskeleton and lipid transport and metabolism COG categories, among others, while genes involved in carbohydrate transport and metabolism were specifically altered in autumn. Overall, transcription patterns were differently altered depending on the exposure time and season, indicating that season should be considered in ecotoxicological studies of metal nanoparticles in mussels.


Assuntos
Nanopartículas Metálicas/toxicidade , Mytilus/efeitos dos fármacos , Polietilenoimina/química , Povidona/química , Prata/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Exposição Dietética/efeitos adversos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Nanopartículas Metálicas/química , Prata/química , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/química
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