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1.
Environ Sci Technol ; 58(12): 5229-5243, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38466915

RESUMO

Silicone-based passive samplers, commonly paired with gas chromatography-mass spectrometry (GC-MS) analysis, are increasingly utilized for personal exposure assessments. However, its compatibility with the biotic exposome remains underexplored. In this study, we introduce the wearable silicone-based AirPie passive sampler, coupled with nontargeted liquid chromatography with high-resolution tandem mass spectrometry (LC-HRMS/MS), GC-HRMS, and metagenomic shotgun sequencing methods, offering a comprehensive view of personalized airborne biotic and abiotic exposomes. We applied the AirPie samplers to 19 participants in a unique deep underwater confined environment, annotating 4,390 chemical and 2,955 microbial exposures, integrated with corresponding transcriptomic data. We observed significant shifts in environmental exposure and gene expression upon entering this unique environment. We noted increased exposure to pollutants, such as benzenoids, polycyclic aromatic hydrocarbons (PAHs), opportunistic pathogens, and associated antibiotic-resistance genes (ARGs). Transcriptomic analyses revealed the activation of neurodegenerative disease-related pathways, mostly related to chemical exposure, and the repression of immune-related pathways, linked to both biological and chemical exposures. In summary, we provided a comprehensive, longitudinal exposome map of the unique environment and underscored the intricate linkages between external exposures and human health. We believe that the AirPie sampler and associated analytical methods will have broad applications in exposome and precision medicine.


Assuntos
Expossoma , Doenças Neurodegenerativas , Hidrocarbonetos Policíclicos Aromáticos , Dispositivos Eletrônicos Vestíveis , Humanos , Espaços Confinados , Transcriptoma , Monitoramento Ambiental/métodos , Silicones
2.
J Gastroenterol Hepatol ; 36(7): 1843-1850, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33274470

RESUMO

BACKGROUND AND AIM: Approximately 42-95% of working channels have been reported to show the presence of residual fluid despite endoscope reprocessing. The aim of this study was to design two novel protocols for cleaning residual simethicone and demonstrate its efficiency by evaluating the residual fluid and cleanliness in the working channels of patient-ready duodenoscopes. METHODS: The designed protocol for cleaning residual simethicone was implemented in manual cleaning and/or high-level disinfection (HLD). The residual fluid inside the working channels was estimated by visual inspection. Adenosine triphosphate (ATP) values were evaluated to determine cleanliness after manual cleaning. RESULTS: Manual cleaning with novel simethicone cleaning protocol demonstrated a significant decrease in fluid droplets (14.6 ± 29.9 vs 0 ± 0, P < 0.001) and ATP values (157 ± 196 relative light units [RLUs] vs 52 ± 41 RLUs, P = 0.031). HLD with simethicone cleaning protocol, using either enzymatic detergent with effective for cleaning simethicone or cleaning time set in the automatic endoscope reprocessor program for 8 min, demonstrated significant decrease in the number of fluid droplets. Follow-up after the implementation of the simethicone cleaning protocol showed a significant decrease in fluid droplets (37.4 ± 41.0 vs 2.1 ± 5.5, P = 0.003) and ATP values (271 ± 268 RLUs vs 82 ± 136 RLUs, P = 0.021). CONCLUSIONS: Simethicone cleaning protocol is advantageous for significantly decreasing fluid droplets and ATP values within endoscope working channels. After manual cleaning with the simethicone cleaning protocol, in particular, no retained fluid droplet was observed in patient-ready duodenoscopes.


Assuntos
Duodenoscópios , Simeticone , Trifosfato de Adenosina , Desinfecção , Contaminação de Equipamentos/prevenção & controle , Humanos
3.
Bioprocess Biosyst Eng ; 43(9): 1599-1607, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32333194

RESUMO

Transaminase responsible for alienating prochiral ketone compound is applicable to asymmetric synthesis of herbicide L-phosphinothricin (L-PPT). In this work, the covalent immobilization of recombinant transaminase from Citrobacter koseri (CkTA) was investigated on different epoxy resins. Using optimum ES-105 support, a higher immobilized activity was obtained via optimizing immobilization process in terms of enzyme loading, coupling time and initial PLP concentration. Crucially, due to blocking unreacted epoxy groups on support surface with amino acids, the reaction temperature of blocked immobilized biocatalyst was enhanced from 37 to 57 °C. Its thermostability at 57 °C was also found to be superior to that of free CkTA. The Km value was shifted from 36.75 mM of free CkTA to 39.87 mM of blocked immobilized biocatalyst, demonstrating that the affinity of enzyme to the substrate has not been apparently altered. Accordingly, the biocatalyst performed the consecutive synthesis of L-PPT for 11 cycles (yields>91%) with retaining more than 91.13% of the initial activity. The seemingly the highest reusability demonstrates this biocatalyst has prospective for reducing the costs of consecutive synthesis of L-PPT with high conversion.


Assuntos
Aminobutiratos/síntese química , Proteínas de Bactérias/química , Citrobacter koseri/enzimologia , Enzimas Imobilizadas/química , Resinas Epóxi/química , Transaminases/química , Proteínas de Bactérias/genética , Citrobacter koseri/genética , Enzimas Imobilizadas/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Transaminases/genética
4.
Langmuir ; 34(29): 8701-8707, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29958496

RESUMO

Developing an effective computed tomography (CT) contrast agent is still a challenging task for precise diagnosis of hepatic carcinoma (HCC). Here, we present the use of acetylated polyethylenimine (PEI)-entrapped gold nanoparticles (Ac-PE-AuNPs) without antifouling modification for negative CT imaging of HCC. PEI was first linked to fluorescein isothiocyanate (FI) and then utilized as a vehicle for the entrapment of AuNPs. The particles were then acetylated to reduce its positive surface potential. The designed Ac-PE-AuNPs were characterized by various techniques. We find that the Ac-PE-AuNPs with a uniform size distribution (mean diameter = 2.3 nm) are colloidally stable and possess low toxicity in the studied range of concentration. Owing to the fact that the particles without additional antifouling modification were mainly gathered in liver, the Ac-PE-AuNPs could greatly improve the CT contrast enhancement of normal liver, whereas poor CT contrast enhancement appeared in liver necrosis region caused by HCC. As a result, HCC could be easily and precisely diagnosed. The designed Ac-PE-AuNPs were demonstrated to have biocompatibility through in vivo biodistribution and histological studies, hence holding an enormous potential to be adopted as an effective negative CT contrast agent for diagnosis of hepatoma carcinoma.


Assuntos
Carcinoma/diagnóstico por imagem , Ouro/química , Neoplasias Hepáticas/diagnóstico por imagem , Nanopartículas Metálicas/química , Polietilenoimina/química , Tomografia Computadorizada por Raios X/métodos , Humanos , Distribuição Tecidual
5.
Biomacromolecules ; 19(6): 2034-2042, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29601720

RESUMO

Development of versatile nanoscale platforms for cancer diagnosis and therapy is of great importance for applications in translational medicine. In this work, we present the use of γ-polyglutamic acid (γ-PGA) nanogels (NGs) to load polypyrrole (PPy) for thermal/photoacoustic (PA) imaging and radiotherapy (RT)-sensitized tumor photothermal therapy (PTT). First, a double emulsion approach was used to prepare the cystamine dihydrochloride (Cys)-cross-linked γ-PGA NGs. Next, the cross-linked NGs served as a reactor to be filled with pyrrole monomers that were subjected to in situ oxidation polymerization in the existence of Fe(III) ions. The formed uniform PPy-loaded NGs having an average diameter of 38.9 ± 8.6 nm exhibited good water-dispersibility and colloid stability. The prominent near-infrared (NIR) absorbance feature due to the loaded PPy endowed the NGs with contrast enhancement in PA imaging. The hybrid NGs possessed excellent photothermal conversion efficiency (64.7%) and stability against laser irradiation, and could be adopted for PA imaging and PTT of cancerous cells and tumor xenografts. Importantly, we also explored the cooperative PTT and X-ray radiation-mediated RT for enhanced tumor therapy. We show that PTT of tumors can be more significantly sensitized by RT using the sequence of laser irradiation followed by X-ray radiation as compared to using the reverse sequence. Our study suggests a promising theranostic platform of hybrid NGs that may be potentially utilized for PA imaging and combination therapy of different types of tumors.


Assuntos
Nanoestruturas/química , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Polímeros/química , Pirróis/química , Radioterapia/métodos , Animais , Feminino , Géis/administração & dosagem , Géis/química , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Neoplasias Experimentais/diagnóstico por imagem , Fotoquimioterapia/instrumentação , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/química , Polimerização , Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Bioconjug Chem ; 28(11): 2692-2697, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29083866

RESUMO

The formation of gold nanoparticle (Au NP)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for computed tomography (CT) imaging of tumors is reported. γ-PGA with carboxyl groups activated by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride is first emulsified to form NGs and then in situ chemically cross-linked with polyethylenimine (PEI)-entrapped Au NPs with partial polyethylene glycol (PEG) modification ([(Au0)200-PEI·NH2-mPEG]). The formed γ-PGA-[(Au0)200-PEI·NH2-mPEG] NGs with a size of 108.6 ± 19.1 nm display an X-ray attenuation property better than commercial iodinated small-molecular-contrast agents and can be uptaken by cancer cells more significantly than γ-PGA-stabilized single Au NPs at the same Au concentrations. These properties render the formed NGs with an ability to be used as an effective contrast agent for the CT imaging of cancer cells in vitro and a tumor model in vivo. The developed hybrid NGs may be promising for the CT imaging or theranostics of different biosystems.


Assuntos
Ouro/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Ácido Poliglutâmico/análogos & derivados , Tomografia Computadorizada por Raios X/métodos , Animais , Ouro/farmacocinética , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanogéis , Nanopartículas/análise , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoimina/química , Polietilenoimina/farmacocinética , Ácido Poliglutâmico/química , Ácido Poliglutâmico/farmacocinética
7.
Adv Healthc Mater ; 13(16): e2303395, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38554036

RESUMO

In the last 30 years, there are ≈60 000 publications about electrospun nanofibers, but it is still unclear whether nanoscale fibers are really necessary for electrospun tissue engineering scaffolds. The present report puts forward this argument and reveals that compared with electrospun nanofibers, microfibers with diameter of ≈3 µm (named as "oligo-micro fiber") are more appropriate for tissue engineering scaffolds owing to their better cell infiltration ability caused by larger pores with available nuclear deformation. To further increase pore sizes, electrospun poly(ε-caprolactone) (PCL) scaffolds are fabricated using latticed collectors with meshes. Fiber orientation leads to sufficient mechanical strength albeit increases porosity. The latticed scaffolds exhibit good biocompatibility and improve cell infiltration. Under aortic conditions in vitro, the performances of latticed scaffolds are satisfactory in terms of the acute systolic hemodynamic functionality, except for the higher regurgitation fraction caused by the enlarged pores. This hierarchical electrospun scaffold with sparse fibers in macropores and oligo-micro fibers in filaments provides new insights into the design of tissue engineering scaffolds, and tissue engineering may provide living heart valves with regenerative capabilities for patients with severe valve disease in the future.


Assuntos
Nanofibras , Poliésteres , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Nanofibras/química , Poliésteres/química , Animais , Humanos , Valvas Cardíacas/fisiologia , Porosidade , Próteses Valvulares Cardíacas , Materiais Biocompatíveis/química
8.
Biomedicines ; 11(11)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-38001996

RESUMO

This review examines the modifying factors affecting bond strength in various bonding scenarios, particularly their relevance to the longevity of dental restorations. Understanding these factors is crucial for improving clinical outcomes in dentistry. Data were gathered from the PubMed database, ResearchGate, and Google Scholar resources, covering studies from 1992 to 2022. The findings suggest that for dentin-resin bonds, minimizing smear layers and utilizing MMP inhibitors to prevent hybrid layer degradation are essential. In the case of resin-resin bonds, reversing blood contamination is possible, but preventing saliva contamination is more challenging, underscoring its critical importance during clinical procedures. Additionally, while pretreatment on ceramics has minimal impact on bond strength, the influence of specific colorings should be carefully considered in treatment planning. This comprehensive review highlights that although established practices recognize significant bond strength factors, ongoing research provides valuable insights to enhance the clinical experience for patients. Once confirmed through rigorous experimentation, these emerging findings should be swiftly integrated into dental practice to improve patient outcomes.

9.
Front Vet Sci ; 9: 985733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187810

RESUMO

Giant pandas are the flagship species in world conservation. Due to bamboo being the primary food source for giant pandas, dental wear is common owing to the extreme toughness of the bamboo fiber. Even though research on tooth enamel wear in humans and domestic animals is well-established, research on tooth enamel wear in giant pandas is scarce. The purpose of this study is to evaluate tooth enamel wear resistance in giant pandas to provide a basis for a better understanding of their evolutionary process. From microscopic and macroscopic perspectives, the abrasion resistance of dental enamel in giant pandas is compared with that of herbivorous cattle and carnivorous dogs in this study. This involves the use of micro-scratch and frictional wear tests. The results show that the boundary between the enamel prism and the enamel prism stroma is well-defined in panda and canine teeth, while bovine tooth enamel appears denser. Under constant load, the tribological properties of giant panda enamel are similar to those of canines and significantly different from those of bovines. Test results show that the depth of micro scratches in giant panda and canine enamel was greater than in cattle, with greater elastic recovery occurring in dogs. Scratch morphology indicates that the enamel substantive damage critical value is greater in pandas than in both dogs and cattle. The analysis suggests that giant panda enamel consists of a neatly arranged special structure that may disperse extrusion stress and absorb impact energy through a series of inelastic deformation mechanisms to cope with the wear caused by eating bamboo. In this study, the excellent wear resistance of giant panda's tooth enamel is verified by wear tests. A possible theoretical explanation of how the special structure of giant panda tooth enamel may improve its wear resistance is provided. This provides a direction for subsequent theoretical and experimental studies on giant panda tooth enamel and its biomaterials.

10.
Nanomedicine (Lond) ; 14(19): 2595-2611, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31361188

RESUMO

Aim: To improve the retention of fluorescein sodium (FS) as a kind of clinical contrast agent for fundus fluorescein angiography (FFA). Materials & methods: Polyethyleneimine (PEI) was designed to synthesize PEI-NHAc-FS nanoparticles (NPs), and the formed NPs were characterized by both physicochemical properties and their effects on FFA. Results: Compared with free FS, PEI-NHAc-FS NPs showed similar optical performance, and could obviously reduce cellular adsorption and uptake both in vitro and in vivo, which could promote the metabolism of NPs in ocular blood vessels. Conclusion: PEI-NHAc-FS NPs represent a smart nanosize fluorescence contrast agent, which hold promising potential for clinical FFA diagnosis, therapy and research work.


Assuntos
Meios de Contraste/química , Angiofluoresceinografia , Fluoresceína/química , Nanopartículas/química , Adsorção/efeitos dos fármacos , Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/patologia , Meios de Contraste/síntese química , Meios de Contraste/farmacologia , Olho/irrigação sanguínea , Olho/diagnóstico por imagem , Olho/patologia , Fluoresceína/farmacologia , Humanos , Polietilenoimina/síntese química , Polietilenoimina/química , Polietilenoimina/uso terapêutico
11.
J Mater Chem B ; 7(3): 368-372, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-32254723

RESUMO

Polydopamine-coated magnetic mesoporous silica nanoparticles have been designed by loading ultrasmall iron oxide nanoparticles within hollow mesoporous silica nanopartricles and then coating polydopamine onto the particle surface. The developed nanoplatform displayed improved colloidal stability, enhanced r1 relaxivity and near infrared absorption feature, affording their use for multimodal cancer theranostics.


Assuntos
Antineoplásicos/farmacologia , Indóis/química , Nanopartículas de Magnetita/química , Neoplasias Mamárias Animais/tratamento farmacológico , Polímeros/química , Dióxido de Silício/química , Nanomedicina Teranóstica , Animais , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Mamárias Animais/patologia , Camundongos , Tamanho da Partícula , Porosidade , Propriedades de Superfície
12.
Acta Biomater ; 86: 406-415, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625415

RESUMO

With great potential in nanomedicine, the integration of a metal organic framework (MOF) with a nanocarrier for smart and versatile cancer theranostics still seeks to expand. In this study, MOF was successfully merged with hollow mesoporous organosilica nanoparticles (HMONs) with a polydopamine (PDA) interlayer to form molecularly organic/inorganic hybridized nanocomposites (HMONs-PMOF). The well-defined nanostructure and favorable biocompatibility of HMONs-PMOF were demonstrated first. Doxorubicin hydrochloride (DOX) and indocyanine green (ICG) were separately loaded into the interior cavity of HMONs and the outer porous shell of MOF with high loading efficacy, respectively. The obtained dual drug-loaded nanocomposites (DI@HMONs-PMOF) displayed favorable photothermal properties and pH/NIR-triggered DOX release manner. Furthermore, in vitro cell experiments validated that HMONs-PMOF can efficiently deliver DOX into cancer cells. Upon entry into cancer cells, the photothermal effect of DI@HMONs-PMOF can induce the lysosome rupture, thereby facilitating the "lysosome escape" process and accelerating the DOX diffusion in the cytoplasm. Benefiting from the iron ion coordinated on PDA and ICG confined in MOF, magnetic resonance (MR) and photoacoustic (PA) dual-modality imaging were performed to verify the effective accumulation of DI@HMONs-PMOF at the tumor site. Interestingly, the results also suggested that the existence of ICG can cooperatively enhance the MR imaging capability of prepared nanocomposites. In addition, the significantly improved synergistic therapeutic efficacy was confirmed both in vitro and in vivo. Thus, our results indicated that the merged nanostructure of HMONs and MOF is promising for versatile cancer theranostics. STATEMENT OF SIGNIFICANCE: Metal organic framework (MOF) has recently emerged as a class of fascinating nanocarriers. The integration of MOF with other nanostructures can endow the new nanoformulation with collective functionality and synergistic performance that are not accessed from single-component nanostructure. Herein, we reported the successful merging of MOF and hollow mesoporous organosilica nanoparticles (HMONs) to form a hollow nanocontainer with a well-defined nanostructure. The large cavity of HMONs and highly porous network of MOF enable high drug loading efficacy. Moreover, the dual-modality magnetic resonance and photoacoustic imaging can be realized, which is also benefited from the merged nanostructure. Overall, we expected this paradigm could pave way for integrating MOF with other nanocarriers to achieve more diverse applications.


Assuntos
Estruturas Metalorgânicas/química , Nanopartículas/química , Neoplasias/terapia , Compostos de Organossilício/química , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Hipertermia Induzida , Indóis/química , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Imageamento por Ressonância Magnética , Nanopartículas/ultraestrutura , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Técnicas Fotoacústicas , Fototerapia , Polímeros/química , Resultado do Tratamento
13.
Biomaterials ; 217: 119326, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31288173

RESUMO

Spinal cord injury (SCI) leads to immediate disruption of neuronal membranes and loss of neurons, followed by extensive secondary injury process. Treatment of SCI still remains a tremendous challenge clinically. Minocycline could target comprehensive secondary injury via anti-inflammatory, anti-oxidant and anti-apoptotic mechanisms. Polyethylene glycol (PEG), a known sealing agent, is able to seal the damaged cell membranes and reduce calcium influx, thereby exerting neuroprotective capacity. Here, an E-selectin-targeting sialic acid - polyethylene glycol - poly (lactic-co-glycolic acid) (SAPP) copolymer was designed for delivering hydrophobic minocycline to achieve combinational therapy of SCI. The obtained SAPP copolymer could self-assemble into micelles with critical micelle concentration being of 13.40 µg/mL, and effectively encapsulate hydrophobic minocycline. The prepared drug-loaded micelles (SAPPM) displayed sustained drug release over 72 h, which could stop microglia activation and exhibited excellent neuroprotective capacity in vitro. The SAPP micelles were efficiently accumulated in the lesion site of SCI rats via the specific binding between sialic acid and E-selectin. Due to the targeting distribution and combinational effect between PEG and minocycline, SAPPM could obviously reduce the area of lesion cavity, and realize more survival of axons and myelin sheaths from the injury, thus distinctly improving hindlimb functional recovery of SCI rats and conferring superior therapeutic effect in coparison with other groups. Our work presented an effective and safe strategy for SCI targeting therapy. Besides, neuroprotective capacity of PEG deserves further investigation on other central nervous system diseases.


Assuntos
Micelas , Ácido N-Acetilneuramínico/química , Polietilenoglicóis/química , Traumatismos da Medula Espinal/terapia , Animais , Terapia Combinada , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Microglia/efeitos dos fármacos , Microglia/patologia , Minociclina/farmacologia , Minociclina/uso terapêutico , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Sprague-Dawley , Medula Espinal/patologia , Medula Espinal/ultraestrutura , Traumatismos da Medula Espinal/tratamento farmacológico
14.
Drug Deliv ; 25(1): 178-186, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29301434

RESUMO

We report the construction and characterization of polyethylenimine (PEI)-entrapped gold nanoparticles (AuNPs) chelated with gadolinium (Gd) ions for targeted dual mode tumor CT/MR imaging in vivo. In this work, polyethylene glycol (PEG) monomethyl ether-modified PEI was sequentially modified with Gd chelator and folic acid (FA)-linked PEG (FA-PEG) was used as a template to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining PEI surface amines. The formed FA-targeted PEI-entrapped AuNPs loaded with Gd (FA-Gd-Au PENPs) were well characterized in terms of structure, composition, morphology, and size distribution. We show that the FA-Gd-Au PENPs with an Au core size of 3.0 nm are water dispersible, colloidally stable, and noncytotoxic in a given concentration range. Thanks to the coexistence of Au and Gd elements within one nanoparticulate system, the FA-Gd-Au PENPs display a better X-ray attenuation property than clinical iodinated contrast agent (e.g. Omnipaque) and reasonable r1 relaxivity (1.1 mM-1s-1). These properties allow the FA-targeted particles to be used as an efficient nanoprobe for dual mode CT/MR imaging of tumors with excellent FA-mediated targeting specificity. With the demonstrated organ biocompatibility, the designed FA-Gd-Au PENPs may hold a great promise to be used as a nanoprobe for CT/MR dual mode imaging of different FA receptor-overexpressing tumors.


Assuntos
Gadolínio/química , Ouro/química , Nanopartículas Metálicas/química , Polietilenoimina/química , Animais , Linhagem Celular Tumoral , Coloides/química , Meios de Contraste/química , Feminino , Ácido Fólico/química , Células HeLa , Células Hep G2 , Humanos , Imageamento por Ressonância Magnética/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Tamanho da Partícula , Polietilenoglicóis/química , Tomografia Computadorizada por Raios X/métodos
15.
Acta Biomater ; 79: 168-181, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30121374

RESUMO

Innterconnected porous architecture is critical for tissue engineering scaffold as well as biomimetic nanofibrous structure. In addition, a paradigm shift is recently taking place in the scaffold design from homogeneous porous scaffold to heterogeneous porous scaffold for the complex tissues. In this study, a versatile and simple one-pot method, dual phase separation, is developed to fabricate macroporous nanofibrous scaffold by phase separating the mixture solutions of immiscible polymer blends without using porogens. The macropores in the scaffold are interconnected, and their size can be tuned by the polymer blend ratio. Moreover, benefiting from the easy operation of dual phase separation technique, an innovative, versatile and facile two-step phase separation method is developed to fabricate heterogeneous porous layered nanofibrous scaffolds with different shapes, such as bilayered tubular scaffold and tri-layered cylindrical scaffold. The bilayered tubular nanofibrous scaffold composed of poly(l-lactic acid) (PLLA)/poly(l-lactide-co-ε-caprolactone) (PLCL) microporous inner layer and PLLA/poly(ε-caprolactone) (PCL) macroporous outer layer matches simultaneously the functional growth of endothelial cells (ECs) and smooth muscle cells (SMCs), and shows the favorable performance for potential small diameter blood vessel application. Therefore, this study provides the novel and facile strategies to fabricate macroporous nanofibrous scaffold and heterogeneous porous layered nanofibrous scaffold for tissue engineering applications. STATEMENT OF SIGNIFICANCE: The fabrication of porous tissue engineering scaffold made of non-water-soluble polymer commonly requires the use of porogen materials. This is complex and time-consuming, resulting in greater difficulty to prepare heterogeneous porous layered scaffold for multifunctional tissues repair, such as blood vessel and osteochondral tissue. Herein, a novel, versatile and simple one-pot dual phase separation technique is developed for the first time to fabricate porous scaffold without using porogens. Simultaneously, it also endows the resultant scaffold with the biomimetic nanofibrous architecture. Based on the easy operation of this dual phase separation technique, a facile two-step phase separation method is also put forward for the first time and applied in fabricating heterogeneous porous layered nanofibrous scaffold for tissue engineering applications.


Assuntos
Prótese Vascular , Nanofibras/química , Engenharia Tecidual/métodos , Animais , Células Cultivadas , Humanos , Masculino , Miócitos de Músculo Liso/citologia , Poliésteres/química , Porosidade , Coelhos , Ratos Sprague-Dawley , Estresse Mecânico , Tela Subcutânea/fisiologia , Alicerces Teciduais/química
16.
ACS Appl Mater Interfaces ; 9(4): 3411-3418, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28067034

RESUMO

We report the synthesis of poly(N-vinylcaprolactam) nanogels (PVCL NGs) loaded with gadolinium (Gd) for tumor MR imaging applications. The PVCL NGs were synthesized via precipitation polymerization using the monomer N-vinylcaprolactam (VCL), the comonomer acrylic acid (AAc), and the degradable cross-linker 3,9-divinyl-2,4,8,10-tetraoxaspiro-[5,5]-undecane (VOU) in aqueous solution, followed by covalently binding with 2,2',2″-(10-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (NH2-DOTA-GA)/Gd complexes. We show that the formed Gd-loaded PVCL NGs (PVCL-Gd NGs) having a size of 180.67 ± 11.04 nm are water dispersible, colloidally stable, uniform in size distribution, and noncytotoxic in a range of the studied concentrations. The PVCL-Gd NGs also display a r1 relaxivity (6.38-7.10 mM-1 s-1), which is much higher than the clinically used Gd chelates. These properties afforded the use of the PVCL-Gd NGs as an effective positive contrast agent for enhanced MR imaging of cancer cells in vitro as well as a subcutaneous tumor model in vivo. Our study suggests that the developed PVCL-Gd NGs could be applied as a promising contrast agent for T1-weighted MR imaging of diverse biosystems.


Assuntos
Nanopartículas/química , Caprolactama/análogos & derivados , Meios de Contraste , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Neoplasias , Polímeros
17.
Int J Pharm ; 319(1-2): 162-8, 2006 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-16687221

RESUMO

The aim of the present study was to find a method to increase oral bioavailability of silymarin, that is to say, by the preparation of silymarin proliposome and to compare the pharmacokinetic characteristics and bioavailability after oral administration of silymarin proliposome and silymarin in beagle dogs. Silymarin proliposome was prepared by the film-deposition on carriers. After the proliposome was contacted with water, the silymarin liposome suspensions formed automatically. The tests of physicochemical properties including SEM, TEM, encapsulation efficiency, dissolution studies, particle size of the reconstituted liposome and stability of the silymarin proliposome were determined by laser-particle-sizer, HPLC, etc. The concentrations of silymarin in plasma of beagle dogs and its pharmacokinetic behaviors after oral administration of silymarin liposome suspensions and silymarin were studied by RP-HPLC. The pharmacokinetic parameters were computed by software program 3p97. The encapsulation efficiency of silymarin liposome could be more than 90%, with an average particle size of about 196.4 nm and the proliposome appeared a very stability at 40 degrees C during 3 months. It was found that mean plasma concentration-time curves of silymarin after oral administration of liposome suspensions and silymarin in beagle dogs were both in accordance with open two-compartments model and first-order absorption. Pharmacokinetic parameters of silymarin proliposome and silymarin in beagle dogs were Tmax both 30 min; Cmax 472.62 and 89.78 ng mL(-1); and AUC0-infinity 2606.21 and 697 ng mL(-1)h, respectively. The high bioavailability of silymarin proliposome could be obtained by oral administration. Silymarin proliposome was stable and did enchance the gastrointestinal absorption of silymarin.


Assuntos
Composição de Medicamentos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacocinética , Silimarina/administração & dosagem , Silimarina/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Cães , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Lipossomos , Masculino , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Modelos Biológicos , Tamanho da Partícula , Substâncias Protetoras/química , Silimarina/sangue , Silimarina/química , Solubilidade
18.
Nanomedicine (Lond) ; 11(13): 1639-52, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27348339

RESUMO

AIM: To synthesize and characterize cost-efficient polyethylenimine-entrapped gold nanoparticles loaded with gadolinium (Gd@Au PENPs) for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging applications. MATERIALS & METHODS: PEGylated PEI modified with gadolinium (Gd) chelator (DOTA) was used as a template to synthesize the Gd@Au PENPs and the particles were well characterized in terms of their physicochemical properties, cytotoxicity and performances in CT and MR imaging in vitro and in vivo. RESULTS: The formed Gd@Au PENPs with low cytotoxicity can be used as a highly efficient contrast agent for dual-mode CT/MR imaging of blood pool and major organs of animals. CONCLUSION: The designed Gd@Au PENPs may be used as a versatile nanoplatform for dual-mode CT/MR imaging of different biological systems.


Assuntos
Meios de Contraste/química , Gadolínio/química , Ouro/química , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Polietilenoimina/química , Animais , Sobrevivência Celular , Meios de Contraste/toxicidade , Humanos , Células KB , Imageamento por Ressonância Magnética , Nanopartículas Metálicas/toxicidade , Camundongos , Imagem Óptica , Propriedades de Superfície , Distribuição Tecidual , Tomografia Computadorizada por Raios X
19.
Nanoscale ; 8(2): 1040-8, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26660033

RESUMO

Imaging guided photothermal agents have attracted great attention for accurate diagnosis and treatment of tumors. Herein, multifunctional NaYF4:Yb/Er@polypyrrole (PPy) core-shell nanoplates are developed by combining a thermal decomposition reaction and a chemical oxidative polymerization reaction. Within such a composite nanomaterial, the core of the NaYF4:Yb/Er nanoplate can serve as an efficient nanoprobe for upconversion luminescence (UCL)/X-ray computed tomography (CT) dual-modal imaging, the shell of the PPy shows strong near infrared (NIR) region absorption and makes it effective in photothermal ablation of cancer cells and infrared thermal imaging in vivo. Thus, this platform can be simultaneously used for cancer diagnosis and photothermal therapy, and compensates for the deficiencies of individual imaging modalities and satisfies the higher requirements on the efficiency and accuracy for diagnosis and therapy of cancer. The results further provide some insight into the exploration of multifunctional nanocomposites in the photothermal theragnosis therapy of cancers.


Assuntos
Nanoestruturas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Fototerapia , Animais , Érbio/química , Células HeLa , Humanos , Ligantes , Luminescência , Camundongos , Microscopia Eletrônica , Nanocompostos/química , Transplante de Neoplasias , Ácido Oleico/química , Oxigênio/química , Polietilenoglicóis/química , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier , Espectroscopia de Luz Próxima ao Infravermelho , Tomografia Computadorizada por Raios X
20.
Colloids Surf B Biointerfaces ; 140: 489-496, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26812636

RESUMO

Development of various cost-effective contrast agents for targeted tumor computed tomography (CT) imaging still remains a great challenge. Herein, we present a facile approach to forming folic acid (FA)-targeted multifunctional gold nanoparticles (AuNPs) using cost-effective branched polyethylenimine (PEI) modified with polyethylene glycol (PEG) as a template for tumor CT imaging applications. In this work, PEI sequentially modified with PEG monomethyl ether, FA-linked PEG, and fluorescein isothiocyanate was used as a template to synthesize AuNPs, followed by transformation of the remaining PEI surface amines to acetamides. The formed FA-targeted PEI-entrapped AuNPs (FA-Au PENPs) were fully characterized. We show that the formed FA-Au PENPs with an Au core size of 2.1 nm are water soluble, colloidally stable, and non-cytotoxic in a given concentration range. Flow cytometry and confocal microscopy data reveal that the FA-Au PENPs are able to target cancer cells overexpressing FA receptors (FAR). Importantly, the developed FA-Au PENPs can be used as a nanoprobe for targeted CT imaging of FAR-expressing cancer cells in vitro and the xenografted tumor model in vivo. With the demonstrated biocompatibility by organ biodistribution and histological studies, the designed FA-Au PENPs may hold great promise to be used as a nanoprobe for CT imaging of different FAR-overexpressing tumors.


Assuntos
Ácido Fólico/química , Ouro/química , Nanopartículas Metálicas/química , Neoplasias/diagnóstico por imagem , Polietilenoglicóis/química , Polietilenoimina/química , Tomografia Computadorizada por Raios X/métodos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Coloides/química , Meios de Contraste/química , Receptores de Folato com Âncoras de GPI/antagonistas & inibidores , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Humanos , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Neoplasias/metabolismo , Solubilidade , Transplante Heterólogo
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