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1.
Int J Nanomedicine ; 15: 6167-6182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922000

RESUMO

Background: Among the novel cancer treatment strategies, combination therapy is a cornerstone of cancer therapy. Materials and Methods: Here, combination therapy with targeted polymer, magnetic hyperthermia and chemotherapy was presented as an effective therapeutic technique. The DOX-loaded PLA-PEG-FA magnetic nanoparticles (nanocarrier) were prepared via a double emulsion method. The nanocarriers were characterized by particle size, zeta potential, morphology, saturation magnetizations and heat generation capacity, and the encapsulation efficiency, drug content and in-vitro drug release for various weight ratios of PLA:DOX. Then, cytotoxicity, cellular uptake and apoptosis level of nanocarrier-treated cells for HeLa and CT26 cells were investigated by MTT assay, flow cytometry, and apoptosis detection kit. Results and Conclusions: The synthesized nanoparticles were spherical in shape, had low aggregation and considerable magnetic properties. Meanwhile, the drug content and encapsulation efficiency of nanoparticles can be achieved by varying the weight ratios of PLA:DOX. The saturation magnetizations of nanocarriers in the maximum applied magnetic field were 59/447 emu/g and 28/224 emu/g, respectively. Heat generation capacity of MNPs and nanocarriers were evaluated in the external AC magnetic field by a hyperthermia device. The highest temperature, 44.2°C, was measured in the nanocarriers suspension at w/w ratio 10:1 (polymer:DOX weight ratio) after exposed to the magnetic field for 60 minutes. The encapsulation efficiency improved with increasing polymer concentration, since the highest DOX encapsulation efficiency was related to the nanocarriers' suspension at w/w ratio 50:1 (79.6 ± 6.4%). However, the highest DOX loading efficiency was measured in the nanocarriers' suspension at w/w ratio 10:1 (5.14 ± 0.6%). The uptake efficiency and apoptosis level of nanocarrier-treated cells were higher than those of nanocarriers (folic acid free) and free DOX-treated cells in both cell lines. Therefore, this targeted nanocarrier may offer a promising nanosystem for cancer-combined chemotherapy and hyperthermia.


Assuntos
Doxorrubicina/farmacologia , Ácido Fólico/farmacologia , Hipertermia Induzida , Nanopartículas de Magnetita/química , Neoplasias/terapia , Polietilenoglicóis/química , Animais , Apoptose/efeitos dos fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Células HeLa , Humanos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Tamanho da Partícula , Polietilenoglicóis/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
2.
J Chromatogr A ; 1626: 461328, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797818

RESUMO

Ferric oxide/carbon (Fe2O3@C) was fabricated via direct carbonization of metal-organic framework of iron (MOF-235) under argon atmosphere. The magnetic Fe2O3 nanoparticles are evenly embedded in porous carbon matrix, while original morphology of MOF-235 was well-maintained. The synthesized Fe2O3@C was used as magnetic sorbent for extracting five benzoylurea insecticides (BUs). The materials exhibited excellent extraction performance, which benefited not only from the strong π-π interaction and hydrophobic interaction (π-conjugated system), but also to the abundant adsorption sites and flexible transport channel (the interconnected 3D porous structure). A three-factor-three-level Box-Behnken design (BBD) was selected to optimize three greatly influential parameters: amount of adsorbent (A), desorption time (B) and volume of desorption solvent (C) by response surface methodology. The established method coupled to HPLC-UV detection showed wide linearity with the range of 0.2-450 µg•L-1, relatively low limits of detection (0.05-0.10 µg•L-1) with the relative standard deviation (RSD) (n = 7) lower t than 5.47%. Moreover, the proposed method was successfully applied to analyze BUs in tea samples and investigate the removal effect of different washing on BUs residues from tea leaf. These results indicated that the synthesized Fe2O3@C is a promising adsorbent material for magnetic solid phase extraction of BUs at trace concentrations from tea samples.


Assuntos
Inseticidas/análise , Nanopartículas de Magnetita/química , Estruturas Metalorgânicas/química , Chá/química , Ureia/análise , Adsorção , Carbono/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Compostos Férricos/química , Inseticidas/isolamento & purificação , Inseticidas/normas , Limite de Detecção , Porosidade , Padrões de Referência , Extração em Fase Sólida , Espectrofotometria Ultravioleta , Chá/metabolismo , Ureia/análogos & derivados , Ureia/isolamento & purificação , Ureia/normas
3.
Int J Nanomedicine ; 15: 4919-4932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764925

RESUMO

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Diagnosing AD before symptoms arise will facilitate earlier intervention. The early diagnostic approaches are thus urgently needed. Methods: The multifunctional nanoparticles W20/XD4-SPIONs were constructed by the conjugation of oligomer-specific scFv antibody W20 and class A scavenger receptor (SR-A) activator XD4 onto superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs' stability and uniformity in size were measured by dynamic light scattering and transmission electron microscopy. The ability of W20/XD4-SPIONs for recognizing Aß oligomers (AßOs) and promoting AßOs phagocytosis was assessed by immunocytochemistry and flow cytometry analysis. The blood-brain barrier permeability of W20/XD4-SPIONs was determined by a co-culture transwell model. The in vivo probe distribution of W20/XD4-SPIONs in AD mouse brains was detected by magnetic resonance imaging (MRI). Results: W20/XD4-SPIONs, as an AßOs-targeted molecular MRI contrast probe, readily reached pathological AßOs regions in brains and distinguished AD transgenic mice from WT controls. W20/XD4-SPIONs retained the property of XD4 for SR-A activation and significantly promoted microglial phagocytosis of AßOs. Moreover, W20/XD4-SPIONs exhibited the properties of good biocompatibility, high stability and low cytotoxicity. Conclusion: Compared with W20-SPIONs or XD4-SPIONs, W20/XD4-SPIONs show the highest efficiency for AßOs-targeting and significantly enhance AßOs uptake by microglia. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to AßOs in AD brains to provide an MRI signal, demonstrating that W20/XD4-SPIONs are promising diagnostic agents for early-stage AD. Due to the beneficial effect of W20 and XD4 on neuropathology, W20/XD4-SPIONs may also have therapeutic potential for AD .


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/imunologia , Imunoconjugados/química , Nanopartículas de Magnetita/química , Receptores Depuradores/metabolismo , Anticorpos de Cadeia Única/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Especificidade de Anticorpos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Diagnóstico Precoce , Imunoconjugados/farmacologia , Imagem por Ressonância Magnética , Camundongos , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/patologia , Nanopartículas Multifuncionais/química , Fagocitose/efeitos dos fármacos , Anticorpos de Cadeia Única/imunologia
4.
Nat Commun ; 11(1): 3903, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764543

RESUMO

Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions. However, the MS detection of low-abundance proteins from blood remains an unsolved challenge due to the extraordinary dynamic range of the blood proteome. Here, we develop an integrated nanoproteomics method coupling peptide-functionalized superparamagnetic nanoparticles (NPs) with top-down MS for the enrichment and comprehensive analysis of cardiac troponin I (cTnI), a gold-standard cardiac biomarker, directly from serum. These NPs enable the sensitive enrichment of cTnI (<1 ng/mL) with high specificity and reproducibility, while simultaneously depleting highly abundant proteins such as human serum albumin (>1010 more abundant than cTnI). We demonstrate that top-down nanoproteomics can provide high-resolution proteoform-resolved molecular fingerprints of diverse cTnI proteoforms to establish proteoform-pathophysiology relationships. This scalable and reproducible antibody-free strategy can generally enable the proteoform-resolved analysis of low-abundance proteins directly from serum to reveal previously unachievable molecular details.


Assuntos
Análise Química do Sangue/métodos , Proteínas Sanguíneas/análise , Espectrometria de Massas/métodos , Proteômica/métodos , Troponina I/sangue , Biomarcadores/sangue , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Nanotecnologia , Processamento de Proteína Pós-Traducional , Proteoma/análise , Reprodutibilidade dos Testes , Albumina Sérica Humana/análise
5.
Int J Nanomedicine ; 15: 4105-4123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606667

RESUMO

Background: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet. Limited data are available regarding issues affecting MNP delivery by this mechanism, such as adhesion to a cellular wall. Research reported here was initiated to better understand the fundamental principles important for successful implementation of rotational magnetic drug targeting (rMDT). Methods: Translational movements of four different iron oxide MNPs were tested, in response to rotation (3 Hz) of a neodymium-boron-iron permanent magnet. MNP clusters moved along biomimetic channels of a custom-made acrylic tray, by surface walking. The effects of different distances and cellular coatings on MNP velocity were analyzed using videography. Dyes (as drug surrogates) and the drug etoposide were transported by rotating MNPs along channels over a 10 cm distance. Results: MNP translational velocities could be predicted from magnetic separation times. Changes in distance or orientation from the magnet produced alterations in MNP velocities. Mean velocities of the fastest MNPs over HeLa, U251, U87, and E297 cells were 0.24 ± 0.02, 0.26 ± 0.02, 0.28 ± 0.01, and 0.18 ± 0.03 cm/sec, respectively. U138 cells showed marked MNP adherence and an 87.1% velocity reduction at 5.5 cm along the channel. Dye delivery helped visualize the effects of MNPs as microdevices for drug delivery. Dye delivery by MNP clusters was 21.7 times faster than by diffusion. MNPs successfully accelerated etoposide delivery, with retention of chemotherapeutic effect. Conclusion: The in vitro system described here facilitates side-by-side comparisons of drug delivery by rotating MNP clusters, on a human scale. Such microdevices have the potential for augmenting drug delivery in a variety of clinical settings, as proposed.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Nanopartículas de Magnetita/química , Microtecnologia/instrumentação , Rotação , Transporte Biológico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Difusão , Etoposídeo/farmacologia , Humanos , Microesferas , Tamanho da Partícula , Tomografia Computadorizada por Raios X
6.
J Chromatogr A ; 1625: 461343, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709308

RESUMO

A simple magnetic dispersive solid-phase extraction (MDSPE) methodology based on mesoporous Fe3O4@ succinic acid nanospheres and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been developed to determine kanamycin (KNM) and neomycin (NEO) contents in Measles, Mumps, and Rubella (MMR) vaccine products. The monodispersed mesoporous Fe3O4 nanospheres with self-assembled carboxyl terminated shell have been prepared via a simple solvothermal method. These as-synthesized mesoporous Fe3O4 nanospheres showed a high magnetic saturation value (Ms = 46 emu g-1) and large specific surface area (111.12 m2 g-1) which made them potential candidates as sorbents in magnetic solid-phase extraction. The adsorption experimental data fitted well with the Freundlich-Langmuir isotherm and followed a pseudo-second-order kinetic model. Moreover influential parameters on extraction efficiency were investigated and optimized. Under optimal conditions, the limits of detection for KNM and NEO were 1.0 and 0.1 ng mL-1, respectively. Recovery assessments using real samples exhibited recoveries in the range of 96.0 ± 4.3 to 101.5 ± 7.1 %, with relative standard deviations of <10.7% (for intra- day) and <14.6% (for inter- day). The proposed method was successfully applied for different spiked and un-spiked MMR vaccine samples. The presented extraction method provides a fast, selective, robust and practical platform for the detection of KNM and NEO in MMR vaccine samples.


Assuntos
Dextranos/química , Canamicina/análise , Nanopartículas de Magnetita/química , Vacina contra Sarampo/análise , Caxumba/imunologia , Nanosferas/química , Neomicina/análise , Vacina contra Rubéola/análise , Espectrometria de Massas em Tandem/métodos , Adsorção , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Cinética , Limite de Detecção , Magnetismo , Nanosferas/ultraestrutura , Reprodutibilidade dos Testes , Extração em Fase Sólida , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Ácido Succínico/química , Fatores de Tempo , Água/química
7.
Int J Nanomedicine ; 15: 4677-4689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669844

RESUMO

Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have displayed multifunctional applications in cancer theranostics following systemic delivery. In an effort to increase the therapeutic potential of local therapies (including focal hyperthermia), nanoparticles can also be administered intratumorally. Therefore, the development of a reliable pharmacokinetic model for the prediction of nanoparticle distribution for both clinically relevant routes of delivery is of high importance. Materials and Methods: The biodistribution of SPIONs (of two different sizes - 130 nm and 60 nm) radiolabeled with zirconium-89 or technetium-99m following intratumoral or intravenous injection was investigated in C57/Bl6 mice bearing subcutaneous GL261 glioblastomas. Based on PET/CT biodistribution data, a novel pharmacokinetic model was established for a better understanding of the pharmacokinetics of the SPIONs after both administration routes. Results: The PET image analysis of the nanoparticles (confirmed by histology) demonstrated the presence of radiolabeled nanoparticles within the glioma site (with low amounts in the liver and spleen) at all investigated time points following intratumoral injection. The mathematical model confirmed the dynamic nanoparticle redistribution in the organism over a period of 72 h with an equilibrium reached after 100 h. Intravenous injection of nanoparticles demonstrated a different distribution pattern with a rapid particle retention in all organs (particularly in liver and spleen) and a subsequent slow release rate. Conclusion: The mathematical model demonstrated good agreement with experimental data derived from tumor mouse models suggesting the value of this tool to predict the real-time pharmacokinetic features of SPIONs in vivo. In the future, it is planned to adapt our model to other nanoparticle formulations to more precisely describe their biodistribution in in vivo model systems.


Assuntos
Compostos Férricos/administração & dosagem , Compostos Férricos/farmacocinética , Glioblastoma/diagnóstico por imagem , Nanopartículas de Magnetita/administração & dosagem , Animais , Feminino , Glioblastoma/patologia , Injeções , Injeções Intravenosas , Nanopartículas de Magnetita/química , Camundongos Endogâmicos C57BL , Modelos Biológicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radioisótopos/farmacocinética , Tecnécio/farmacocinética , Nanomedicina Teranóstica/métodos , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto , Zircônio/farmacocinética
8.
Nat Commun ; 11(1): 3637, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686685

RESUMO

We report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as well as endow a responsive MRI capability by using a hybrid core-shell vesicles (HCSVs). HCSVs are prepared by loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers the release of AA, resulting in the increase of ferrous ions through the redox reaction between AA and IONCs. A significant tumor suppression is achieved by Fenton reaction-mediated ferroptosis-like cell-death. The oxidative stress induced by the Fenton reaction leads to the exposure of calreticulin on tumor cells, which leads to dendritic cells maturation and the infiltration of cytotoxic T lymphocytes in tumor. Furthermore, the depletion of ferric ions during treatment enables monitoring of the Fe reaction in MRI-R2* signal change. This strategy provides a perspective on ferroptosis-based immunotherapy.


Assuntos
Ferroptose/efeitos dos fármacos , Campos Magnéticos , Nanopartículas de Magnetita , Neoplasias/terapia , Animais , Ácido Ascórbico/farmacologia , Calreticulina/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Compostos Férricos/química , Imunoterapia/métodos , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Estresse Oxidativo , Linfócitos T Citotóxicos/metabolismo
9.
Ecotoxicol Environ Saf ; 203: 111002, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32684519

RESUMO

In this paper, environmental friendly magnetic composite adsorbent (MSAL), exhibited excellent adsorption capacity for lead ions in the solution, was successfully prepared using two non-biologically toxic materials including L-cysteine and sodium alginate. Batch experiments were carried out to discuss the influences of different parameters like pH, adsorbent dosing, initial concentration and contact time on adsorption performance. Results showed sorption process followed by pseudo-second-order kinetic model and Langmuir isotherm model, which suggested the adsorption was limited by the chemical process dominated by the molecular layer. Based on Langmuir isotherm model, the maximum Pb(Ⅱ) adsorption capacity was about 330 mg/g, which was better than a large amount of other lead adsorbents. Various analytical methods, such as SEM-EDS, FTIR, VSM, TGA, XPS and Zeta potential, were applied to characterize the performance of this adsorbent as well as exploring the adsorption mechanism. Characterization results found this adsorbent exhibited a large contact area, good thermal stability, sufficient adsorption sites and excellent magnetic responsiveness. It also has been found that the adsorption mechanism mainly included ion exchange and chelation between amino, carboxyl and lead ions. After 5 cycles, the adsorption capacity decreased from 98.04% to 87.40% and still maintained at high level. The average iron ions concentration in the adsorbed solution sample or in the regeneration solution were 0.34 mg/L and 0.15 mg/L. Overall, all above results imply that MSAL is a promising reusable adsorbent for removing Pb(Ⅱ) in solution.


Assuntos
Chumbo/análise , Nanopartículas de Magnetita/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Alginatos/química , Cisteína/química , Óxido Ferroso-Férrico/química , Concentração de Íons de Hidrogênio , Cinética , Fenômenos Magnéticos , Propriedades de Superfície
10.
J Vis Exp ; (160)2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32628159

RESUMO

In the present work, the synthesis of magnetic nanoparticles, its coating with SiO2, followed by its amine functionalization with (3-aminopropyl)triethoxysilane (APTES) and its conjugation with deferoxamine, a siderophore recognized by Yersinia enterocolitica, using a succinyl moiety as a linker are described. Magnetic nanoparticles (MNP) of magnetite (Fe3O4) were prepared by solvothermal method and coated with SiO2 (MNP@SiO2) using the Stöber process followed by functionalization with APTES (MNP@SiO2@NH2). Then, feroxamine was conjugated with the MNP@SiO2@NH2 by carbodiimide coupling to give MNP@SiO2@NH2@Fa. The morphology and properties of the conjugate and intermediates were examined by eight different methods including powder X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and energy dispersive X-Ray (EDX) mapping. This exhaustive characterization confirmed the formation of the conjugate. Finally, in order to evaluate the capacity and specificity of the nanoparticles, they were tested in a capture bacteria assay using Yersinia enterocolitica.


Assuntos
Desferroxamina/química , Nanopartículas de Magnetita/química , Propilaminas/química , Sideróforos/química , Silanos/química , Dióxido de Silício/química , Yersinia enterocolitica
11.
Int J Nanomedicine ; 15: 3605-3620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547017

RESUMO

Purpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field. Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections. Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head. Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/efeitos adversos , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/citologia , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Hemólise/efeitos dos fármacos , Humanos , Indóis/química , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Polímeros/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X , Proteína de Morte Celular Associada a bcl/metabolismo
12.
Biosens Bioelectron ; 165: 112356, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32510339

RESUMO

Circle-to-circle amplification (C2CA) is a specific and precise cascade nucleic acid amplification method consisting of more than one round of padlock probe ligation and rolling circle amplification (RCA). Although C2CA provides a high amplification efficiency with a negligible increase of false-positive risk, it contains several step-by-step operation processes. We herein demonstrate a homogeneous and isothermal nucleic acid quantification strategy based on C2CA and optomagnetic analysis of magnetic nanoparticle (MNP) assembly. The proposed homogeneous circle-to-circle amplification eliminates the need for additional monomerization and ligation steps after the first round of RCA, and combines two amplification rounds in a one-pot reaction. The second round of RCA produces amplicon coils that anneal to detection probes grafted onto MNPs, resulting in MNP assembly that can be detected in real-time using an optomagnetic sensor. The proposed methodology was applied for the detection of a synthetic complementary DNA of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2, also known as 2019-nCoV) RdRp (RNA-dependent RNA polymerase) coding sequence, achieving a detection limit of 0.4 fM with a dynamic detection range of 3 orders of magnitude and a total assay time of ca. 100 min. A mathematical model was set up and validated to predict the assay performance. Moreover, the proposed method was specific to distinguish SARS-CoV and SARS-CoV-2 sequences with high similarity.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas Biossensoriais/instrumentação , Infecções por Coronavirus/diagnóstico , DNA Complementar/análise , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Pneumonia Viral/diagnóstico , Técnicas Biossensoriais/métodos , Desenho de Equipamento , Estudos de Viabilidade , Humanos , Limite de Detecção , Magnetismo/instrumentação , Magnetismo/métodos , Nanopartículas de Magnetita/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Pandemias
13.
Int J Nanomedicine ; 15: 3333-3346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494133

RESUMO

Background and Objective: Cancer cells accumulate high concentrations of reactive oxygen species as a result of their faster and uninhibited metabolic activity. Cancer chemotherapeutic agents release an excess of severe adverse reactions as a result of targeting normal cells. This demands an improvement in targeted drug-delivery systems to selectively discharge anticancer drugs in the vicinity of such highly metabolically and mitotically active cells. Materials and Methods: Here, magnetic nanoparticles were synthesized by a traditional co-precipitation technique. Fe3O4@OA-CS-5-FLU-NPs were synthesized by an easy and rapid in situ loading method. The proposed Fe3O4@OA-CS-5-FLU-NPs were productively prepared as well as characterized by various spectroscopic and microscopic studies. Results: The targeted drug release profile of the Fe3O4@OA-CS-5-FLU-NPs was studied in the presence of ROS including H2O2 and pH induction. The released product, Fe3O4@OA-CS-5-FLU-NP, exhibited desirable levels of cytotoxicity and demonstrated morphological changes and inhibition of colony formation for A549 and HeLa S3 cancer cells. The IC50 values at 24 hours were 12.9 and 23 µg/mL, respectively. Conclusion: In summary, results from the MTT assay, fluorescence staining as well as colony formation assays, revealed that the Fe3O4@OA-CS-5-FLU-NPs were active and safe for anticancer biomedical applications. In summary, the present investigation provides a powerful nanostructured based system for improved cancer theranostics that should be further studied.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos , Compostos Férricos/química , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Nanopartículas de Magnetita/ultraestrutura , Neoplasias/patologia , Ácido Oleico/química , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X
14.
Food Chem ; 326: 126969, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32438229

RESUMO

Biocompatible magnetic molecularly imprinted polymers (BMMIPs) were prepared with Zein for the first time, and were used to enrich tetracycline compounds selectively. Innovative combination of BMMIPs and electrochemistry to obtain lower detection line to satisfy industrial detection demands. Using Zein as the crosslinking agent, the polymers were synthesized on the surface of Fe3O4 particles. The scanning electron microscope, transmission electron microscope and X-ray diffraction technologies were used to characterize BMMIPs. Through optimization, BMMIPs attained large adsorption capacity (236.40 mg/g) with fast kinetics (40 min) and followed the Langmuir isotherm and pseudo-second-order kinetic models. BMMIPs had good recognition ability, the selective factors of oxytetracycline, chlortetracycline, doxycycline were 4.78, 4.23, and 3.39, respectively. Excellent linearity was attained in the range of 0.025-500 µg/mL, with low detection limits and low quantitation limits of 0.025 and 0.083 µg/mL. According to our exploring, BMMIPs was ideal materials for enrichment of tetracycline in complex biological samples.


Assuntos
Materiais Biocompatíveis/química , Contaminação de Alimentos/análise , Leite/química , Impressão Molecular/métodos , Tetraciclinas/análise , Adsorção , Animais , Antibacterianos/análise , Antibacterianos/química , Antibacterianos/isolamento & purificação , Técnicas Eletroquímicas , Análise de Alimentos/métodos , Limite de Detecção , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Polímeros/química , Tetraciclina/análise , Tetraciclina/química , Tetraciclina/isolamento & purificação , Tetraciclinas/química , Tetraciclinas/isolamento & purificação , Difração de Raios X , Zeína/química
15.
Medicine (Baltimore) ; 99(19): e19972, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384447

RESUMO

The objective of this proof-of-concept study was to demonstrate the targeted delivery of erythropoietin (EPO) using magnetically guided magnetic nanoparticles (MNPs).MNPs consisting of a ferric-ferrous mixture (FeCl3·6H2O and FeCl2·4H2O) were prepared using a co-precipitation method. The drug delivery system (DDS) was manufactured via the spray-drying technique using a nanospray-dryer. The DDS comprised 7.5 mg sodium alginate, 150 mg MNPs, and 1000 IU EPO.Scanning electron microscopy revealed DDS particles no more than 500 nm in size. Tiny particles on the rough surfaces of the DDS particles were composed of MNPs and/or EPO, unlike the smooth surfaces of the only alginate particles. Transmission electron microscopy showed the tiny particles from 5 to 20 nm in diameter. Fourier-transform infrared spectroscopy revealed DDS peaks characteristic of MNPs as well as of alginate. Thermal gravimetric analysis presented that 50% of DDS weight was lost in a single step around 500°C. The mode size of the DDS particles was approximately 850 nm under in vivo conditions. Standard soft lithography was applied to DDS particles prepared with fluorescent beads using a microchannel fabricated to have one inlet and two outlets in a Y-shape. The fluorescent DDS particles reached only one outlet reservoir in the presence of a neodymium magnet. The neurotoxicity was evaluated by treating SH-SY5Y cells in 48-well plates (1 × 10 cells/well) with 2 µL of a solution containing sodium alginate (0.075 mg/mL), MNPs (1.5 mg/mL), or sodium alginate + MNPs. A cell viability assay kit was used to identify a 93% cell viability after MNP treatment and a 94% viability after sodium alginate + MNP treatment, compared with the control. As for the DDS particle neurotoxicity, a 95% cell viability was noticed after alginate-encapsulated MNPs treatment and a 93% cell viability after DDS treatment, compared with the control.The DDS-EPO construct developed here can be small under in vivo conditions enough to pass through the lung capillaries with showing the high coating efficiency. It can be guided using magnetic control without displaying significant neurotoxicity in the form of solution or particles.


Assuntos
Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Eritropoetina/farmacologia , Nanopartículas de Magnetita , Materiais Revestidos Biocompatíveis/farmacologia , Meios de Contraste , Fármacos Hematológicos/farmacologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Teste de Materiais , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Propriedades de Superfície , Traumatismos do Sistema Nervoso/terapia
16.
Int J Nanomedicine ; 15: 2583-2603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368042

RESUMO

Introduction: Over the past several years, nano-based therapeutics were an effective cancer drug candidate in order to overcome the persistence of deadliest diseases and prevalence of multiple drug resistance (MDR). Methods: The main objective of our program was to design organosilane-modified Fe3O4/SiO2/APTS(~NH2) core magnetic nanocomposites with functionalized copper-Schiff base complex through the use of (3-aminopropyl)triethoxysilane linker as chemotherapeutics to cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), TEM, and vibrating sample magnetometer (VSM) techniques. All analyses corroborated the successful synthesis of the nanoparticles. In the second step, all compounds of magnetic nanoparticles were validated as antitumor drugs through the conventional MTT assay against K562 (myelogenous leukemia cancer) and apoptosis study by Annexin V/PI and AO/EB. The molecular dynamic simulations of nanoparticles were further carried out; afterwards, the optimization was performed using MM+, semi-empirical (AM1) and Ab Initio (STO-3G), ForciteGemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017. Results: The results showed that the anti-cancer activity was barely reduced after modifying the surface of the Fe3O4/SiO2/APTS nanoparticles with 2-hydroxy-3-methoxybenzaldehyde as Schiff base and then Cu(II) complex. The apoptosis study by Annexin V/PI and AO/EB stained cell nuclei was performed that apoptosis percentage of the nanoparticles increased upon increasing the thickness of Fe3O4 shell on the magnetite core. The docking studies of the synthesized compounds were conducted towards the DNA and Topoisomerase II via AutoDock 1.5.6 (The Scripps Research Institute, La Jolla, CA, USA). Conclusion: Results of biology activities and computational modeling demonstrate that nanoparticles were targeted drug delivery system in cancer treatment.


Assuntos
Cobre/química , Compostos Férricos/síntese química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Propilaminas/síntese química , Bases de Schiff/síntese química , Silanos/síntese química , Dióxido de Silício/síntese química , Apoptose , Núcleo Celular/metabolismo , DNA/química , DNA Topoisomerases Tipo II/química , Compostos Férricos/química , Humanos , Células K562 , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Propilaminas/química , Bases de Schiff/química , Silanos/química , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
17.
Int J Nanomedicine ; 15: 2617-2631, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368044

RESUMO

Introduction: As widely used chemotherapeutic agents, platinum compounds have several therapeutic challenges, such as drug resistance and adverse effects. Theranostic systems, macromolecular or colloidal therapeutics with companion diagnostics, not only address controlled drug delivery but also enable real-time monitoring of tumor sites. Methods: Synthesis of magnetic mesoporous silica nanoparticles (MMSNs) was performed for dual magnetic resonance imaging and drug delivery. MMSN surfaces were modified by imidazoline groups (MMSN-Imi) for cisplatin (Cis-Pt) conjugation via free N-termini to achieve well-controlled drug-release kinetics. Cis-Pt adsorption isotherms and drug-release profile at pH 5 and 7.4 were investigated using inductively coupled plasma atomic emission spectroscopy. Results: MMSN-Imi showed a specific surface area of 517.6 m2 g-1, mean pore diameter of 3.26 nm, and saturated magnetization of 53.63 emu/g. A relatively high r2/r1 relaxivity value was obtained for MMSN-Imi. The nanoparticles provided high Cis-Pt loading with acceptable loading capacity (~30% w:w). Sustained release of Cis-Pt under acidic conditions led to specific inhibitory effects on the growth of human epithelial ovarian carcinoma cells, determined using MTT assays. Dual acridine orange-propidium iodide staining was investigated, confirming induction of apoptosis and necrotic cell death. Conclusion: MMSN-Imi exhibited potential for applications in cancer chemotherapy and combined imaging.


Assuntos
Sistemas de Liberação de Medicamentos , Imidazolinas/química , Nanopartículas de Magnetita/química , Platina/administração & dosagem , Dióxido de Silício/química , Nanomedicina Teranóstica , Adsorção , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Morte Celular , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Liberação Controlada de Fármacos , Difusão Dinâmica da Luz , Hemólise , Humanos , Cinética , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Nitrogênio/química , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Temperatura , Difração de Raios X
18.
Phys Med Biol ; 65(12): 125003, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32311682

RESUMO

We are developing magnetic nanoparticle (NP) methods to characterize inflammation and infection in vivo. Peritoneal infection in C57BL/6 mice was used as a biological model. An intraperitoneal NP injection was followed by measurement of magnetic nanoparticle spectroscopy of Brownian rotation (MSB) spectra taken over time. MSB measures the magnetization of NPs in a low frequency alternating magnetic field. Two groups of three mice were studied; each group had two infected mice and one control with no infection. The raw MSB signal was compared with two derived metrics: the NP relaxation time and number of NPs present in the sensitive volume of the receive coil. A four compartment dynamic model was used to relate those physical properties to the relevant biological processes including phagocytic activity and migration. The relaxation time increased over time for all of the mice as the NPs were absorbed. The NP number decreased over time as the NPs were cleared from the sensitive volume of the receive coil. The composite p-values for all three rate constants were significant: raw signal, 0.0002, relaxation, <10-16 and local NP clearance, <10-16. However, not all the individual mice had significant changes: Only half the infected mice had significantly different rate constants for raw signal reduction. All infected mice had significantly smaller relaxation time constants. All but one of the infected mice had significantly lower rate constants for local clearance. Relaxation is affected by both phagocytic activity, edema and temperature changes and it should be possible to better isolate those effects to more completely characterize inflammation using more advanced MSB methods. The MSB NP signal can be used to identify inflammation in vivo because it has the unique ability to monitor phagocytic absorption through relaxation measurements.


Assuntos
Inflamação/diagnóstico , Nanopartículas de Magnetita/química , Animais , Campos Magnéticos , Camundongos , Camundongos Endogâmicos C57BL , Rotação , Análise Espectral
19.
Microvasc Res ; 130: 104007, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32305349

RESUMO

Magnetic nanoparticle targeting in tumor areas is examined by an integrated consideration of the transport steps from the microcirculation to the vascular walls, through their pores and into the interstitium. Brownian, flow- and magnetically induced forces and fluxes are compared on the basis of order-of-magnitude estimates and numerical simulations. The main resistance to nanoparticle transport is found to be within the interstitium, since fluxes there are much smaller than the extravasation fluxes, and the latter are much smaller than the convective-diffusive ones within the microvasculature. For typical nanoparticle sizes, magnetic properties and strengths of magnetic fields as in MRI equipment, magnetic targeting is rather unlikely to play a significant role in directing nanoparticles towards vascular walls or through vascular pores. However, magnetic drift can have an effect within the interstitium and a tangible overall outcome, despite the fact that typical magnetic forces are smaller than Brownian ones or interstitial flow convective forces. The reason behind such an effect has to do with the much larger length scales involved in interstitial transport. Magnetic drift creates a front of large nanoparticle concentrations, flooding the inadequately perfused and poorly accessible tumor area. On the basis of time-scale estimates, it is suggested that sequential cycles of magnetic nanoparticle dosage may help in more efficient access of cell layers ever closer to the tumor center. The present results may assist in the quest for optimal parameters and conditions, given the conflicting requirements for particles small enough to evade hydrodynamic and steric hindrances in vascular pores and the interstitium, yet large enough to bear a substantial magnetic load.


Assuntos
Antineoplásicos/metabolismo , Portadores de Fármacos , Magnetismo , Nanopartículas de Magnetita/química , Microvasos/metabolismo , Modelos Biológicos , Nanomedicina , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Transporte Biológico , Permeabilidade Capilar , Difusão , Composição de Medicamentos , Humanos , Hidrodinâmica , Neoplasias/tratamento farmacológico , Análise Numérica Assistida por Computador
20.
Artigo em Inglês | MEDLINE | ID: mdl-32222675

RESUMO

C60-based magnetic nanospheres were synthesized by coating Fe3O4 nanospheres with silica, then modifying with 3-aminopropyltriethoxysilane as a linker and a C60 fullerene stationary phase. The morphologies, magnetic properties, infrared absorption and carbon content of magnetic nanospheres were studied by TEM, VSM, FTIR and carbon and sulfur analyzer. The magnetic nanospheres were employed for the magnetic solid-phase extraction (MSPE) of 16 polycyclic aromatic hydrocarbons (PAHs) in nine Chinese herbal medicines. The analyses were conducted by isotope dilution gas chromatography-mass spectrometry. The main parameters influencing the extraction, including extraction solvent, adsorbent amount, and extraction time were optimized. Method validation showed that the limit of detection (LOD) was 0.02-0.11 µg/kg, and the limit of quantification (LOQ) was 0.07-0.36 µg/kg. The spiked recoveries rates for 16 PAHs in white peony root were 84.7-107.2%. The relative standard deviation (RSD) was 1.7-8.4%. The established method was further used for the determination 16 PAHs in nine Chinese herbal medicines. Total content of 16 PAHs varied from 73.6 µg/kg (fructus lycii) to 2172.6 µg/kg (astragalus root). The results indicate that the pollution of PAHs in Chinese herbal medicines is serious. The established method can effective detect PAHs contamination in Chinese herbal medicines.


Assuntos
Medicamentos de Ervas Chinesas/análise , Fulerenos/química , Isótopos/química , Nanopartículas de Magnetita/química , Nanosferas/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Adsorção , Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , Fenômenos Magnéticos , Propilaminas/química , Silanos/química , Dióxido de Silício/química , Extração em Fase Sólida/métodos , Propriedades de Superfície
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