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1.
Biomacromolecules ; 25(5): 3112-3121, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38651274

RESUMO

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 µg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed ß-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.


Assuntos
Antibacterianos , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Escherichia coli/efeitos dos fármacos , Animais , Testes de Sensibilidade Microbiana , Polieletrólitos/química , Polieletrólitos/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Conformação Proteica em alfa-Hélice , Micelas , Infecções por Escherichia coli/tratamento farmacológico , Hemólise/efeitos dos fármacos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Camundongos , Ácido Poliglutâmico/química , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/farmacologia , Humanos
2.
J Med Virol ; 95(12): e29296, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38054540

RESUMO

Mpox is still spreading globally and is mostly reported to be transmitted by skin and mucosal contact. However, transmission through contact with fomites, contaminated objects, or surfaces has been reported in general population. Evaluation of the stability of mpox virus (MPXV) on different surfaces is important to minimize mpox transmission. In the study, the stability of MPXV on different kinds of commonly contacted surfaces was determined. MPXV was observed to have a surface-dependent stability pattern. Viable virus was detected on both glass and stainless steel for up to 5 days, and on plastic surfaces for up to 3 days. In contrast, no viable MPXV was detected on wooden board and cardboard, which are porous and water-absorbent surfaces, after 1 and 2 days of incubation, respectively. In addition, MPXV nucleic acids were more stable and showed better correlation with viral titers on stainless steel, plastic, and glass. The results indicate that fomite transmission of MPXV is plausible. Moreover, the stability of MPXV was highly surface-dependent and more stable on smooth surfaces, which could provide more information for minimizing the transmission of mpox and emphasize the significance of environmental disinfection in mpox prevention and control.


Assuntos
Mpox , Humanos , Monkeypox virus , Aço Inoxidável , Desinfecção , Fômites
3.
Biomacromolecules ; 24(9): 3985-3995, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37642585

RESUMO

Proteins used as building blocks to template nanostructures with manifold morphologies have been widely reported. Understanding their self-assembly and reassembly mechanism is important for designing functional biomaterials. Herein, we show that enzyme-hydrolyzed α-lactalbumin (α-lac) can self-assemble into either nanotubes in the presence of Ca2+ ions or nanospheres in the absence of Ca2+ in solution. Remarkably, such assembled α-lac nanotubes can be elongated by adding preassembled α-lac nanospheres and Ca2+ solution, which suggests that the self-assembled α-lac nanospheres undergo disassembly and reassembly processes into existing nanotube nuclei. By performing atomic force microscopy (AFM), transmission electron microscopy (TEM), and confocal laser scanning microscopy (CLSM), it indicates that there is an equilibrium among nanotubes, nanospheres, hydrolyzed α-lac, and Ca2+ in solution. The structural transition between nanotubes and nanospheres is driven from a less stable structure into a more stable structure determined by the conditions. During the transition from nanospheres into nanotubes, the hydrolyzed α-lac in nanospheres transfers into helical ribbon form at both nanotube extremities. Then helical ribbons close into mature nanotubes, extending the length of the initial nuclei. Besides, by dilution or adding ethylene glycol bis(2-aminoethyl ether) tetraacetic acid (EGTA), the decreased Ca2+ concentration in solution drives the Ca2+ dissociating from nanotubes into solution, leading to the transitions from nanotubes into nanospheres. The reversible transformation between nanotubes and nanospheres is achieved by adjusting the pH value from 7.5 to 5.0 and back to 7.5. This is because the stability of nanotubes decreases from pH 7.5 to 5 but increases from 5 to 7.5. Significantly, this approach can be used for the fabrication of various responsive nanomaterials from the same starting material.


Assuntos
Nanosferas , Nanoestruturas , Nanotubos , Íons , Materiais Biocompatíveis
4.
Mikrochim Acta ; 186(8): 537, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31317277

RESUMO

A capillary monolith consisting of poly[N-(4-vinyl)-benzyl iminodiacetic acid-co-divinylbenzene-co-N,N'-methylene bisacrylamide), referred to as poly(VBIDA-DVB-Bis), has been prepared. It is shown to be an efficient sorbent for the enrichment of Co(II) and Cd(II). The two ions are completely retained by the monolith in the pH range from 4.0 to 9.0. The breakthrough curve tests were adopted to evaluate the adsorption performance of the monolith towards Co(II) and Cd(II). A dose-response model was used to describe the breakthrough curves of the two ions at different initial concentrations. The adsorption capacities for Co(II) and Cd(II) are 1.54 and 1.73 mg·m-1 at a concentration level of 2.5 mg·L-1, respectively. The enrichment factor is 100, and the required sample volume is 5 mL. Following elution of the two ions with 0.5 M HNO3, they were quantified by ICP-MS. The limits of detection in a 1 mL sample are 0.35 ng·L-1 for Co(II) and 0.44 ng·L-1 for Cd(II). The method was applied to the determination of Co(II) and Cd(II) in spiked rice, human urine and seawater samples. Graphical abstract Schematic representation of a monolithic copolymer prepared from N-(4-vinyl)-benzyl iminodiacetic acid (VBIDA), divinylbenzene (DVB) and N,N'-methylene bisacrylamide (Bis) and its application for selective capturing of cadmium(II) and cobalt(II) from complex sample matrices prior to their determination by ICP-MS.


Assuntos
Acrilamidas/química , Cádmio/análise , Cobalto/análise , Iminoácidos/química , Polímeros/química , Compostos de Vinila/química , Adsorção , Cádmio/química , Cádmio/urina , Cobalto/química , Cobalto/urina , Humanos , Espectrometria de Massas , Oryza/química , Água do Mar/análise
5.
Int J Mol Sci ; 20(17)2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450644

RESUMO

Auxin response factors (ARFs) are important regulators modulating the expression of auxin-responsive genes in various biological processes in plants. In the Populus genome, a total of 39 ARF members have been identified, but their detailed functions are still unclear. In this study, six poplar auxin response factor 2 (PtrARF2) members were isolated from P. trichocarpa. Expression pattern analysis showed that PtrARF2.1 is highly expressed in leaf tissues compared with other PtrARF2 genes and significantly repressed by exogenous auxin treatment. PtrARF2.1 is a nuclear-localized protein without transcriptional activation activity. Knockdown of PtrARF2.1 by RNA interference (RNAi) in poplars led to the dwarf plant, altered leaf shape, and reduced size of the leaf blade, while overexpression of PtrARF2.1 resulted in a slight reduction in plant height and the similar leaf phenotype in contrast to the wildtype. Furthermore, histological staining analysis revealed an ectopic deposition of lignin in leaf veins and petioles of PtrARF2.1-RNAi lines. RNA-Seq analysis showed that 74 differential expression genes (DEGs) belonging to 12 transcription factor families, such as NAM, ATAF and CUC (NAC), v-myb avian myeloblastosis viral oncogene homolog (MYB), ethylene response factors (ERF) and basic helix-loop-helix (bHLH), were identified in PtrARF2.1-RNAi leaves and other 24 DEGs were associated with the lignin biosynthetic pathway. Altogether, the data indicate that PtrARF2.1 plays an important role in regulating leaf development and influences the lignin biosynthesis in poplars.


Assuntos
Regulação da Expressão Gênica de Plantas , Lignina/biossíntese , Desenvolvimento Vegetal/genética , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Populus/fisiologia , Fatores de Transcrição/genética , Sequência de Aminoácidos , Vias Biossintéticas/genética , Clonagem Molecular , Especificidade de Órgãos , Fenótipo , Filogenia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Populus/classificação , Análise de Sequência de DNA , Fatores de Transcrição/metabolismo , Transcriptoma
6.
Nanotechnology ; 26(36): 365103, 2015 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-26291977

RESUMO

A novel locally injectable, biodegradable, and thermo-sensitive hydrogel made from chitosan and ß-glycerophosphate salt was prepared. It incorporated polyethylenimine (PEI)-modified super-paramagnetic graphene oxide (GO/IONP/PEI) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. Doxorubicin (DOX) was mixed into the hydrogel which was pre-loaded on GO/IONP/PEI to create a drug delivery system DOX-GO/IONP/PEI-gel. In addition to the evaluation of in vitro and in vivo antitumor activities, the physicochemical properties, magnetic properties and DOX release profile of the DOX-GO/IONP/PEI-gel were determined. The aqueous solution of the hydrogel showed a sol-gel transition behavior depending on temperature changes. Magnetization loops indicated the super-paramagnetic properties of GO/IONP/PEI. Compared with free DOX, DOX-GO/IONP/PEI could efficiently pass through cell membranes, leading to more apoptosis and demonstrating higher antitumor efficacy on MCF-7 cells in vitro. Furthermore, DOX-GO/IONP/PEI-gel intratumorally injected (i.t.) showed high antitumor efficacy on tumor-bearing mice in vivo, with no obvious toxicity. The antitumor efficacy was higher when combined with an alternating magnetic field (AMF), showing that DOX-GO/IONP/PEI-gel under AMF has great potential for cancer magnetic hyperthermia therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Doxorrubicina/administração & dosagem , Grafite/química , Hidrogéis/administração & dosagem , Hipertermia Induzida/métodos , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Apoptose , Quitosana/química , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Glicerofosfatos/química , Humanos , Hidrogéis/química , Células MCF-7 , Campos Magnéticos , Camundongos , Polietilenoimina/química , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Sci Total Environ ; 912: 169571, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38142997

RESUMO

The application of organic fertilizers is becoming an undeniable source of microplastics and antibiotic resistance genes (ARGs) in agricultural soils. The complex microbial activity further transfers resistance genes and their host bacteria to agricultural products and throughout the entire food chain. Therefore, the current main focus is on reducing the abundance of microplastics and ARGs in organic fertilizers at the source, as well as managing microplastics and ARGs in soil. The control of microplastic abundance in organic fertilizers is currently only achieved through pre-composting selection and other methods. However, there are still many shortcomings in the research on the distribution characteristics, propagation and diffusion mechanisms, and control technologies of ARGs, and some key scientific issues still need to be urgently addressed. The high-temperature composting of organic waste can effectively reduce the abundance of ARGs in organic fertilizers to a certain extent. However, it is also important to consider the spread of ARGs in residual antibiotic-resistant bacteria (ARB). This article systematically explores the pathways and interactions of microplastics and resistance genes entering agricultural soils through the application of organic fertilizers. The removal of microplastics and ARGs from organic fertilizers was discussed in detail. Based on the limitations of existing research, further investigation in this area is expected to provide valuable insights for the development and practical implementation of technologies aimed at reducing soil microplastics and resistance genes.


Assuntos
Microplásticos , Plásticos , Fertilizantes/análise , Genes Bacterianos , Antagonistas de Receptores de Angiotensina , Microbiologia do Solo , Esterco/microbiologia , Inibidores da Enzima Conversora de Angiotensina , Solo , Bactérias/genética , Antibacterianos
8.
Opt Express ; 21(15): 17931-40, 2013 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-23938665

RESUMO

We demonstrate a silicon-based optoelectronic integrated circuit (OEIC) for label-free bio/chemical sensing application. Such on-chip OEIC sensor system consists of optical grating couplers for vertical light coupling into silicon waveguides, a thermal-tunable microring as a tunable filter, an exposed microring as an optical label-free sensor, and a Ge photodetector for a direct electrical readout. Different from the conventional wavelength-scanning method, we adopt low-cost broadband ASE light source, together with the on-chip tunable filter to generate sliced light source. The effective refractive index change of the sensing microring induced by the sensing target is traced by scanning the supplied electrical power applied onto the tracing microring, and the detected electrical signal is read out by the Ge photodetector. For bulk refractive index sensing, we demonstrate using such OEIC sensing system with a sensitivity of ~15 mW/RIU and a detection limit of 3.9 µ-RIU, while for surface sensing of biotin-streptavidin, we obtain a surface mass sensitivity of S(m) = ~192 µW/ng·mm(-2) and a surface detection limit of 0.3 pg/mm(2). The presented OEIC sensing system is suitable for point-of-care applications.


Assuntos
Biopolímeros/análise , Condutometria/instrumentação , Eletrônica/instrumentação , Sistemas Microeletromecânicos/instrumentação , Refratometria/instrumentação , Semicondutores , Silício/química , Técnicas Biossensoriais/instrumentação , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Coloração e Rotulagem , Integração de Sistemas
9.
Food Res Int ; 169: 112851, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37254424

RESUMO

Electrospinning has attracted extensive attention among various nanofabrication technologies owing to its ability to produce nanofiber structures with unique properties, such as high specific surface area and porosity, as well as tunable fiber morphology and mechanical properties. The most representative spinning raw materials include natural polymers and synthetic polymers. Owing to the sustainable development strategies, more and more researchers focus on natural polymers. Among natural polymers, wheat gluten (WG) nanofibers have recently attracted much attention owing to its high specific surface area, superior biocompatibility, and unique viscoelasticity. This review summarizes the composition and characteristics of WG, the physical and chemical indicators of a WG electrospinning solution, the main influencing factors in the WG electrospinning process and a characterizations of WG nanofibers. Finally, the review also outlines the applications of WG nanofibers in drug release, biological scaffold, and active food packaging.


Assuntos
Materiais Biocompatíveis , Nanofibras , Materiais Biocompatíveis/química , Triticum , Polímeros/química , Nanofibras/química , Glutens
10.
Macromol Rapid Commun ; 33(22): 1952-7, 2012 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-22907724

RESUMO

A photoresponsive microgel is designed by the combination of a noncovalent assembly strategy with a covalent cross-linking method. End-functionalized poly(ethylene glycol) with azobenzene [(PEG-(Azo)(2))] was mixed with acrylate-modified ß-CD (ß-CD-MAA) to form photoresponsive inclusion complex through host-guest interaction. The above photoresponsive complex was cross-linked by thiol-functionalized PEG (PEG-dithiol) via Michael addition click reaction. The photoreversibility of resulted microgel was studied by TEM, UV-Vis spectroscopy, and (1)H NMR measurements. The characterization results indicated that the reversible size changes of the microgel could be achieved by alternative UV-Vis irradiations with good repeatability.


Assuntos
Géis/química , Compostos de Sulfidrila/química , Compostos Azo/química , Luz , Polietilenoglicóis/química , Raios Ultravioleta , beta-Ciclodextrinas/química
11.
Colloids Surf B Biointerfaces ; 214: 112469, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35339902

RESUMO

The high adhesive property of polydopamine (PDA) has spurred various hydrogels for biological and medical applications. Herein, a dual-catalytic redox system was constructed by using the inner dynamic redox-activity of PDA and free radical initiator ammonium persulfate (APS) to initiate the polymerization of acrylic acid (AA) monomer to obtain Fe-PDA hydrogels within 2 h at room temperature. Fe-PDA NPs functions as both initiator to activate APS to generate free radicals and promotes the formation of the hydrogel and dynamic cross-linking mediator between the polymer chains. The tensile strength and ductility of the obtained hydrogels vary with the content of Fe-PDA NPs. Hydrogel with 0.15 wt% of Fe-PDA NPs has the highest tensile strength (~0.62 MPa) and hydrogel with 0.6 wt% of Fe-PDA NPs has the highest elongation, about ~650%. The introduction of PDA NPs imparts PAA hydrogel with reproducible adhesive properties and self-healing ability. The doped iron ion further endows hydrogel enhanced photothermal properties (up to 160 â„ƒ with 808 nm laser irradiation for 120 s) and conductivity.


Assuntos
Adesivos , Hidrogéis , Indóis , Polímeros
12.
J Drug Target ; 30(7): 767-776, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35379059

RESUMO

The nano-drug delivery system activated by the tumour microenvironment (TME) can effectively treat tumours with low toxicity. Based on a high level of reductive GSH in TME and the different coordination properties of Fe ions, this project intended to prepare a GSH-activated cascade catalytic nanoreactor for breast cancer treatment using Fe3+/Fe2+ as the molecular switch. In this study, the glucose oxidase (GOx) loaded iron alginate nano hydrogel (FeAlg/GOx) was prepared by the simple one-step titration method. Results showed that FeAlg/GOx could remain stable during in vivo circulation to avoid hypoglycaemia. When it reached the targeted tumour site, reductive GSH can reduce Fe3+ to Fe2+. Thereafter, FeAlg/GOx nanogel was broken and GOx was released to consume the essential nutrient glucose (Glu) to achieve tumour starvation therapy. Next, the substrate H2O2 generated by the reaction between GOx and Glu can be catalysed by Fe2+ to produce highly cytotoxic •OH in situ, which could further kill tumour cells. The in vivo pharmacodynamics results demonstrated that compared with the control group (V/V0 = 8.36 ± 1.73), FeAlg/GOx group showed the most significant anti-tumour effect with V/V0 of 3.08 ± 1.06. In conclusion, this "inactivated" FeAlg/GOx nanogel can be converted into "activated" therapeutic substances in situ to achieve starvation-chemodynamic combined treatment for breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Glucose , Glucose Oxidase , Humanos , Peróxido de Hidrogênio/química , Nanogéis , Nanotecnologia , Neoplasias/tratamento farmacológico , Microambiente Tumoral
13.
ACS Appl Mater Interfaces ; 14(35): 39787-39798, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36001127

RESUMO

Stimuli-activatable nanomaterials hold significant promise for tumor-specific drug delivery by recognizing the internal or external stimulus. Herein, we reported a dual-responsive and biodegradable polypeptide nanoparticle (PPTP@PTX2 NP) for combinatory chemotherapy and photodynamic therapy (PDT) of breast cancer. The NPs were engineered by encapsulating diselenide bond linked dimeric prodrug of paclitaxel (PTX2) in an intracellular acidity-activatable polypeptide micelle. Specifically, the acid-responsive polypeptide was synthesized by grafting a tetraphenyl porphyrin (TPP) photosensitizer and N,N-diisopropylethylenediamine (DPA) onto the poly(ethylene glycol)-block-poly(glutamic acid) diblock copolymer by the amidation reaction, which self-assembled into micellar NPs and was activated inside the acidic endocytic vesicles to perform PDT. The paclitaxel dimer can be stably loaded into the polypeptide NPs and be restored by PDT inside the tumor cells. The formed PPTP@PTX2 NPs remained inert during blood circulation and passively accumulated in the tumor foci, which could be activated within the endocytic vesicles via acid-triggered protonation of DPA groups to generate fluorescence signal and release PTX2 in 4T1 murine breast tumor cells. Upon 660 nm laser irradiation, the activated NPs carried out PDT via TPP and chemotherapy via PTX to induce apoptosis of 4T1 cells and thereby efficiently inhibited 4T1 tumor growth and prevented metastasis of tumor cells.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Camundongos , Micelas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Paclitaxel , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/química
14.
J Control Release ; 352: 673-684, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36374646

RESUMO

Diabetes mellitus is a long-term chronic disease characterized by abnormal high level blood glucose (BG). An artificial closed-loop system that mimics pancreatic ß-cells and releases insulin on demand has potential to improve the therapeutic efficiency of diabetes. Herein, a lectin Concanavalin A modified oxidized starch nanogel was designed to regulate glucose dynamically according to different glucose concentrations. The nanogels were formed by double cross-linking the Concanavalin A and glucose units on oxidized starch via specific binding and amide bonds to achieve the high drug loading and glucose responsiveness. The results showed that oxidized starch nanogels prolonged the half-life of antidiabetic peptide drug exenatide and released it in response to high BG concentrations. It could absorb BG at a high level and maintain glucose homeostasis. Besides, the oxidized starch nanogels performed well in recovering regular BG level from hyperglycemia state and maintaining in euglycemia state that fitted in a biological rhythm. In addition, the nanogels showed high biocompatibility in vivo and could improve plasma half-life and therapeutic efficacy of exenatide. Overall, the nanogels protected peptide drugs from degradation in plasma as a glucose-responsive platform showing a high potential for peptide drugs delivery and antidiabetic therapy.


Assuntos
Glicemia , Glucose , Nanogéis , Exenatida , Amido , Concanavalina A , Hipoglicemiantes , Portadores de Fármacos/química
15.
ACS Macro Lett ; 10(1): 154-160, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35548982

RESUMO

We report on enhancing crystallization and heat resistance of poly(l-lactic acid) (PLLA) by d-sorbitol as a small molecule nucleating agent via melt blending. During the reheating process, the cold crystallization disappeared and the crystallinity of nucleated PLLA exceeded 50%. The heat deflection temperature of PLLA was elevated from 56 to 132 °C by simply increasing the mold temperature (90 °C) without an additional annealing treatment. We also observed the polymorphic crystals of PLLA during melt crystallization, i.e., the coexistence of hexagonal and lenticular crystals, along with their various geometrical aggregates in addition to plenty of conventional spherulites. On the basis of the fact that the nonisothermal crystallization temperature of PLLA (110 °C at a cooling rate of 10 °C/min) was higher than the melting point of d-sorbitol (about 93 °C), we speculated that d-sorbitol promoted the crystallization of PLLA through a homogeneous nucleation mechanism.


Assuntos
Temperatura Alta , Sorbitol , Cristalização , Poliésteres/química
16.
ACS Appl Mater Interfaces ; 12(6): 6978-6990, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31951366

RESUMO

Tumor vasculature and enhanced autophagy collectively provide the source of nutrients for tumor growth, invasion, and metastasis. Blocking the source of nutrients will be a novel and promising antitumor approach. Herein, we exploited an intelligent nanogel (CA4-FeAlg/HCQ) with a positioning remodeling feature to precisely kill A549 cancer cells in all directions based on frontal and rear attack strategies. CA4-FeAlg/HCQ nanogels could remain stable during blood circulation. When they reached the tumor vascular site, the vascular blocker combretastatin A4 (CA4) would be released at first to exert an antiangiogenic effect. Thereafter, FeAlg/HCQ disintegrated into small nanogels (<30 nm) for tumor deep penetration. Once small nanogels entered tumor cells, FeAlg/HCQ would undergo phase remodeling (gel to sol) to release the autophagy inhibitor hydroxychloroquine (HCQ) quickly. The autophagy induced by CA4 can be effectively inhibited by HCQ to achieve synergistic treatment of tumors. In addition, after Fe3+ in FeAlg being reduced to Fe2+, it catalyzed intratumoral hydrogen peroxide (H2O2) to generate cytotoxic hydroxyl radicals (·OH), which further strengthened the antitumor effect. The in vivo pharmacodynamic result revealed that CA4-FeAlg/HCQ showed the greatest therapeutic effect, with the final V/V0 of 0.40 ± 0.10. Our study provided a hopeful platform for rational and precise tumor treatment, which may be of great significance in the combined pharmacotherapy.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Autofagia/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Nanogéis/química , Neoplasias/tratamento farmacológico , Inibidores da Angiogênese/química , Animais , Antineoplásicos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Feminino , Humanos , Camundongos Endogâmicos BALB C
17.
Anal Chim Acta ; 1090: 64-71, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31655647

RESUMO

Using carcinoembryonic antigen (CEA) imprinted polymerized ionic liquid hydrogel as a recognition element and hollow gold nanoballs/MoSe2 nanosheets as a photoactive element, a photoelectrochemical (PEC) sensing platform was successfully fabricated. To accomplish the imprinted process under room temperature to maintain the biological activity and the configuration of CEA, and thus to improve the sensing performances, 3-{[{4-N,N-Bis[(carbamoyl)ethylmethacrylate]butyl}((carbamoyl)amino)ethyl methacrylate] -propyl}-1-ethenyl-1H-imidazol-3-ium bromide (BCCPEimBr) ionic liquid was synthesized. By using BCCPEimBr ionic liquid as the functional monomer, CEA as the template, a molecularly imprinted hydrogel film was prepared on a hollow gold nanoballs/MoSe2 nanosheets modified glassy carbon electrode surface. After removing the template, a CEA imprinted photoelectrochemical sensor was successfully fabricated. The imprinted PEC sensor shows good selectivity, sensitivity and stability towards CEA, produces a linear response in the concentration range from 0.05 to 5.0 ng mL-1 and shows a detection limit of 11.2 pg mL-1 (S/N = 3) under the optimized conditions. The imprinted PEC sensor was used to determine CEA in clinical human serum samples accurately. The procedure for the imprinted PEC sensing platform can be used for other biomolecules just by substituting the template.


Assuntos
Antígeno Carcinoembrionário/sangue , Hidrogéis/química , Líquidos Iônicos/química , Nanopartículas Metálicas/química , Nanocompostos/química , Polímeros/química , Técnicas Biossensoriais/métodos , Dissulfetos/química , Técnicas Eletroquímicas/métodos , Ouro/química , Ouro/efeitos da radiação , Humanos , Limite de Detecção , Nanopartículas Metálicas/efeitos da radiação , Impressão Molecular , Molibdênio/química , Fotoquímica/métodos , Reprodutibilidade dos Testes
18.
Eur J Pharm Sci ; 140: 105071, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525433

RESUMO

Multidrug resistance (MDR) is a major reason for anticancer chemotherapy failure, and P-glycoprotein (P-gp) over-expressing on tumor cells is considered as the important target to overcome MDR. Emerging reports have showed that vitamin E (VE) can cause significant reversal of MDR due to inhibition of ATPase activity. Accordingly, we synthesized hyaluronic acid (HA) conjugated vitamin E succinate (VES) polymer, which can self-assemble into micelles and thus achieve high drug (paclitaxel (PTX) used as model drug) encapsulation as well as tumor accumulation owing to the enhanced permeability and retention (EPR) effect and HA active targeting ability. In addition, the linker between HA and VES utilized in this work was disulfide bond with reduction-sensitive property, which would respond to high glutathione (GSH) concentration in tumor cytoplasmic environment and trigger HA-CYS-VES polymer disassociation and drug release. In vitro, PTX loaded HA-CYS-VES demonstrated enhanced cytotoxicity, high apoptosis-inducing activities and reversal effects of PTX on MCF-7/Adr cells, compared to PTX. Also, cellular uptake and intracellular PTX accumulation tests displayed that PTX loaded HA-CYS-VES could more efficiently enter tumor cells and selectively release drug in cytosol so as to facilitate its function on microtubule. More importantly, PTX loaded HA-CYS-VES showed better tumor targeting ability, improved antitumor efficacy and low adverse effects on tumor-bearing mice. In conclusion, PTX loaded HA-CYS-VES exhibited a great potential for reversing MDR in anticancer chemotherapeutics.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácido Hialurônico/química , Micelas , Paclitaxel/química , alfa-Tocoferol/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Citosol/metabolismo , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular/métodos , Polímeros/química
19.
Talanta ; 181: 104-111, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29426487

RESUMO

Hydrogen sulfide (H2S) is a critical biological messenger in numerous physiological and pathophysiological processes. Small-molecule fluorescent probes combined with fluorescent microscopy have been developed for the sensitive detection of H2S. Here, we designed and synthesized a long-wavelength BODIPY-based probe (TMSDNPOB) based on the thiolysis of dinitrophenyl ether according to photo-induced electron transfer theory and the results of computational calculation. 4,4-Difluoro-8-phenyl-1,5,7-trimethyl-3-(4-(2,4-dinitrophenoxy)styryl- 4-bora-3a,4a-diaza-s-indacene (TMSDNPOB) is nearly non-fluorescent, but the reaction product (TMSHOB) emits strong red fluorescence at 592nm when excited at 574nm. The long wavelengths of the designed probe indicate low background interference from biological matrix and little photo damage on fluorescence imaging of H2S. With the advantages of the turn-on probe for H2S including high sensitivity, high selectivity, good biocompatibility and low toxicity, the probe has been used for imaging H2S in living cells and liver tissues.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Fígado/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Compostos de Boro/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Microscopia Confocal , Células RAW 264.7 , Fatores de Tempo
20.
J Chromatogr A ; 1160(1-2): 114-9, 2007 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-17466319

RESUMO

A simple, rapid and sensitive method for the determination of hexanal and heptanal in plasma by high-performance liquid chromatography (HPLC) has been developed, which is based on polymer monolith microextraction (PMME) with in situ derivatization. 2,4-dinitrophenylhydrazine (DNPH) as a derivatizing reagent was first adsorbed on a poly (methacrylic acid-co-ethylene glycol dimethacrylate) (MAA-EGDMA) monolith, and then microextraction was performed simultaneously with derivatization on the monolith. The several parameters affecting the in situ derivatization simultaneously with PMME were investigated, including the flow rate, pH, buffer concentration, and temperature. The whole pretreatment process can be accomplished within 8 min. The limits of detection for hexanal and heptanal were found to be 2.4 and 3.6 nmol/L, respectively. The recoveries in plasma sample were in the range of 83-87% with the inter- and intra-day precisions less than 6.8%. This method was successfully applied to the analysis of hexanal and heptanal in plasma samples from different cancer patients.


Assuntos
Aldeídos/sangue , Técnicas de Química Analítica/métodos , Polímeros/isolamento & purificação , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Fenil-Hidrazinas/química , Polímeros/química , Temperatura
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