Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.926
Filtrar
1.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360714

RESUMO

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Campos Magnéticos , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Feminino , Humanos , Letrozol/química , Letrozol/farmacocinética , Letrozol/farmacologia , Lipossomos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Proteínas de Neoplasias/metabolismo
2.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200350

RESUMO

A considerable interest in cancer research is represented by the development of magnetic nanoparticles based on biofunctionalized polymers for controlled-release systems of hydrophobic chemotherapeutic drugs targeted only to the tumor sites, without affecting normal cells. The objective of the paper is to present the synthesis and in vitro evaluation of the nanocomposites that include a magnetic core able to direct the systems to the target, a polymeric surface shell that provides stabilization and multi-functionality, a chemotherapeutic agent, Paclitaxel (PTX), and a biotin tumor recognition layer. To our best knowledge, there are no studies concerning development of magnetic nanoparticles obtained by partial oxidation, based on biotinylated N-palmitoyl chitosan loaded with PTX. The structure, external morphology, size distribution, colloidal and magnetic properties analyses confirmed the formation of well-defined crystalline magnetite conjugates, with broad distribution, relatively high saturation magnetization and irregular shape. Even if the ability of the nanoparticles to release the drug in 72 h was demonstrated, further complex in vitro and in vivo studies will be performed in order to validate the magnetic nanoparticles as PTX delivery system.


Assuntos
Antineoplásicos Fitogênicos/química , Biotina/química , Quitosana/análogos & derivados , Nanopartículas de Magnetita/química , Paclitaxel/química , Linhagem Celular Tumoral , Quitosana/química , Coloides/química , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Células MCF-7 , Polímeros/química
3.
Artigo em Inglês | MEDLINE | ID: mdl-34224966

RESUMO

In this work, a novel strategy was developed for separation and enrichment of sibiskoside by dummy molecular imprinting technology and magnetic separation technology. The structural analogue geniposide was selected as the dummy template, using 4-vinylpyridine as the functional monomer, ethylene glycol dimethacrylate as the cross-linking agent, and acetonitrile as the porogen. The molecularly imprinted layer was formed on the surface of the magnetic carrier to prepare dummy template molecularly imprinted polymers (DMIPs) with a core-shell structure. The DMIPs were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and Vibration sample magnetometer (VSM). The results of adsorption kinetics experiments and isothermal adsorption experiments showed that DMIPs can reach adsorption equilibrium in a short period of time and the maximum adsorption capacity can reach 14.67 mg/g. The imprinting factor was 2.08. Compared with the andrographolide, polydatin, arbutin, caffeic acid, neohesperidin dihydrochalcone and quercetin, DMIPs have good adsorption capacity for the sibiskoside. And the reusability was better. After the adsorption of DMIPs, the purity of sibiskoside in the crude extracts from Sibiraea angustata increased to 78%. It provided a basis for the further development and utilization of Sibiraea angustata as well as the separation and enrichment of monoterpenes.


Assuntos
Monoterpenos Acíclicos , Glicosídeos , Nanopartículas de Magnetita/química , Polímeros Molecularmente Impressos/química , Rosaceae/química , Monoterpenos Acíclicos/análise , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/isolamento & purificação , Adsorção , Cromatografia Líquida de Alta Pressão , Glicosídeos/análise , Glicosídeos/química , Glicosídeos/isolamento & purificação , Extratos Vegetais/química
4.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202245

RESUMO

Cancer-based magnetic theranostics has gained significant interest in recent years and can contribute as an influential archetype in the effective treatment of cancer. Owing to their excellent biocompatibility, minute sizes and reactive functional surface groups, magnetic nanoparticles (MNPs) are being explored as potential drug delivery systems. In this study, MgFe2O4 ferrite MNPs were evaluated for their potential to augment the delivery of the anticancer drug doxorubicin (DOX). These MNPs were successfully synthesized by the glycol-thermal method and functionalized with the polymers; chitosan (CHI), polyvinyl alcohol (PVA) and polyethylene glycol (PEG), respectively, as confirmed by Fourier transform infrared (FTIR) spectroscopy. X-ray diffraction (XRD) confirmed the formation of the single-phase cubic spinel structures while vibrating sample magnetometer (VSM) analysis confirmed the superparamagnetic properties of all MNPs. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed small, compact structures with good colloidal stability. CHI-MNPs had the highest DOX encapsulation (84.28%), with the PVA-MNPs recording the lowest encapsulation efficiency (59.49%). The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) cytotoxicity assays conducted in the human embryonic kidney (HEK293), colorectal adenocarcinoma (Caco-2), and breast adenocarcinoma (SKBR-3) cell lines showed that all the drug-free polymerized MNPs promoted cell survival, while the DOX loaded MNPs significantly reduced cell viability in a dose-dependent manner. The DOX-CHI-MNPs possessed superior anticancer activity (<40% cell viability), with approximately 85.86% of the drug released after 72 h in a pH-responsive manner. These MNPs have shown good potential in enhancing drug delivery, thus warranting further optimizations and investigations.


Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Nanopartículas de Magnetita , Neoplasias/tratamento farmacológico , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Células CACO-2 , Quitosana/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Compostos Férricos/química , Células HEK293 , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Polietilenoglicóis/química , Álcool de Polivinil/química
5.
Molecules ; 26(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203543

RESUMO

In this paper, the steady electrically conducting hybrid nanofluid (CuO-Cu/blood) laminar-mixed convection incompressible flow at the stagnation-point with viscous and gyrotactic microorganisms is considered. Additionally, hybrid nanofluid flow over a horizontal porous stretching sheet along with an induced magnetic field and external magnetic field effectsthat can be used in biomedical fields, such as in drug delivery and the flow dynamics of the microcirculatory system. This investigation can also deliver a perfect view about the mass and heat transfer behavior of blood flow in a circulatory system and various hyperthermia treatments such as the treatment of cancer. The simple partial differential equations (PDEs) are converted into a series of dimensional ordinary differential equations (ODEs), which are determined using appropriate similarities variables (HAM). The influence of the suction or injection parameter, mixed convection, Prandtl number, buoyancy ratio parameter, permeability parameter, magnetic parameter, reciprocal magnetic prandtl number, bioconvection Rayleigh number, coupled stress parameter, thermophoretic parameter, Schmidt number, inertial parameter, heat source parameter, and Brownian motion parameter on the concentration, motile microorganisms, velocity, and temperature is outlined, and we study the physical importance of the present problem graphically.


Assuntos
Sistemas de Liberação de Medicamentos , Campos Magnéticos , Nanopartículas de Magnetita , Modelos Biológicos , Neoplasias/tratamento farmacológico , Animais , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/metabolismo
6.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207182

RESUMO

Globally, cancer is the second (to cardiovascular diseases) leading cause of death. Regardless of various efforts (i.e., finance, research, and workforce) to advance novel cancer theranostics (diagnosis and therapy), there have been few successful attempts towards ongoing clinical treatment options as a result of the complications posed by cancerous tumors. In recent years, the application of magnetic nanomedicine as theranostic devices has garnered enormous attention in cancer treatment research. Magnetic nanoparticles (MNPs) are capable of tuning the magnetic field in their environment, which positively impacts theranostic applications in nanomedicine significantly. MNPs are utilized as contrasting agents for cancer diagnosis, molecular imaging, hyperfusion region visualization, and T cell-based radiotherapy because of their interesting features of small size, high reactive surface area, target ability to cells, and functionalization capability. Radiolabelling of NPs is a powerful diagnostic approach in nuclear medicine imaging and therapy. The use of luminescent radioactive rhenium(I), 188/186Re, tricarbonyl complexes functionalised with magnetite Fe3O4 NPs in nanomedicine has improved the diagnosis and therapy of cancer tumors. This is because the combination of Re(I) with MNPs can improve low distribution and cell penetration into deeper tissues.


Assuntos
Nanopartículas de Magnetita/química , Neoplasias/diagnóstico , Rênio/química , Nanomedicina Teranóstica/métodos , Animais , Humanos , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Compostos Organometálicos/química
7.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207373

RESUMO

A nucleic acid aptamer that specifically recognizes methicillin-resistant Staphylococcus aureus (MRSA) has been immobilized on magnetic nanoparticles to capture the target bacteria prior to mass spectrometry analysis. After the MRSA species were captured, they were further eluted from the nanoparticles and identified using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The combination of aptamer-based capture/enrichment and MS analysis of microorganisms took advantage of the selectivity of both techniques and should enhance the accuracy of MRSA identification. The capture and elution efficiencies for MRSA were optimized by examining factors such as incubation time, temperature, and elution solvents. The aptamer-modified magnetic nanoparticles showed a capture rate of more than 90% under the optimized condition, whereas the capture rates were less than 11% for non-target bacteria. The as-prepared nanoparticles exhibited only a 5% decrease in the capture rate and a 9% decrease in the elution rate after 10 successive cycles of utilization. Most importantly, the aptamer-modified nanoparticles revealed an excellent selectivity towards MRSA in bacterial mixtures. The capture of MRSA at a concentration of 102 CFU/mL remained at a good percentage of 82% even when the other two species were at 104 times higher concentration (106 CFU/mL). Further, the eluted MRSA bacteria were successfully identified using MALDI mass spectrometry.


Assuntos
Aptâmeros de Nucleotídeos/química , Nanopartículas de Magnetita/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Staphylococcus aureus Resistente à Meticilina/citologia , Técnica de Seleção de Aptâmeros/métodos
8.
ACS Appl Mater Interfaces ; 13(27): 31514-31526, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34213305

RESUMO

Micro/nanomotors (MNMs), which propel by transforming various forms of energy into kinetic energy, have emerged as promising therapeutic nanosystems in biomedical applications. However, most MNMs used for anticancer treatment are only powered by one engine or provide a single therapeutic strategy. Although double-engined micromotors for synergistic anticancer therapy can achieve more flexible movement and efficient treatment efficacy, their design remains challenging. In this study, we used a facile preparation method to develop enzymatic/magnetic micromotors for synergetic cancer treatment via chemotherapy and starvation therapy (ST), and the size of micromotors can be easily regulated during the synthetic process. The enzymatic reaction of glucose oxidase, which served as the chemical engine, led to self-propulsion using glucose as a fuel and ST via a reduction in the energy available to cancer cells. Moreover, the incorporation of Fe3O4 nanoparticles as a magnetic engine enhanced the kinetic power and provided control over the direction of movement. Inherent pH-responsive drug release behavior was observed owing to the acidic decomposition of drug carriers in the intracellular microenvironment of cancer cells. This system displayed enhanced anticancer efficacy owing to the synergetic therapeutic strategies and increased cellular uptake in a targeted area because of the improved motion behavior provided by the double engines. Therefore, the demonstrated micromotors are promising candidates for anticancer biomedical microsystems.


Assuntos
Glucose Oxidase/metabolismo , Fenômenos Magnéticos , Microtecnologia/métodos , Neoplasias/terapia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia
9.
Chem Commun (Camb) ; 57(51): 6249-6252, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34059853

RESUMO

A hydrophilic probe is employed to enrich exosomes from three kinds of cancer cells by TiO2-phosphate interaction and exosomal glycoproteins by hydrophilic interaction in succession. The probe performs efficiently in both the enrichment processes. And the analytical results confirm that unique exosomal glycoproteins can distinguish parent exosomes from others.


Assuntos
Exossomos/metabolismo , Glicoproteínas/análise , Sondas Moleculares/metabolismo , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , Glutationa/química , Glutationa/metabolismo , Glicoproteínas/metabolismo , Glicosilação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas de Magnetita/química , Sondas Moleculares/química , Proteômica/métodos , Titânio/química
10.
Int J Biol Macromol ; 185: 287-296, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34153359

RESUMO

Cellulose microcrystalline (MCC) was widely used in pharmaceutical and chemical industries because of its low degree of polymerization and large specific surface area. As its modified form, dialdehyde cellulose (DAC) was used for cross-linking and immobilizing Rhizopus lipase together with magnetic nanoparticles (MNPs) due to its active aldehyde groups. In this study, in order to maintain the original enzyme activity as much as possible and improve the stability of lipase, the Rhizopus lipase was successfully immobilized on the magnetic dialdehyde cellulose nanoparticles (MDC). Specifically, the immobilization conditions including dosage of DAC, concentration of enzyme, immobilization time and temperature together with pH value of the reaction medium were optimized. Maximum immobilization yield (60.03 ± 0.49%) and recovery activity (88.88 ± 0.61%) can be obtained under the optimal process conditions. The changes in secondary structures of immobilized enzyme revealed the increment in conformational rigidity, which can be reflected in temperature and pH stability as well as tolerance of organic reagents. Additionally, the recovery activity of immobilized enzyme still reached 50.60 ± 0.59% after 30 d of storage and 52.10 ± 0.57% retained after 6 cycles. These results indicated the ideal application prospect of MDC in immobilized enzymes.


Assuntos
Celulose/análogos & derivados , Lipase/química , Nanopartículas de Magnetita/química , Rhizopus/enzimologia , Celulose/química , Estabilidade Enzimática , Enzimas Imobilizadas/química , Proteínas Fúngicas/química , Concentração de Íons de Hidrogênio , Estrutura Secundária de Proteína , Temperatura , Tempo
11.
J Mater Chem B ; 9(24): 4915-4928, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34100480

RESUMO

The promise of biocompatible magnetic nanoparticles with high magnetic saturation in the implementation as drug carriers and hyperthermia agents has generated significant interest in functionalised cobalt nanoparticles. Carboxylic acid coatings on metallic nanoparticles have been shown as an attractive option owing to their respectable stability and biocompatibility. However, only limited information is available on the molecular mechanism leading to the formation of such protective coatings. In this study, ab initio molecular dynamics simulations have been used to unravel the functionalisation mechanism starting from a neutral cobalt cluster and valeric acid molecules. Three stages were detected in the coating process: (i) rapid initial adsorption of acid molecules, (ii) simultaneous adsorption of new molecules and dissociation of those already interacting with the cluster, and, finally, (iii) grouping of dissociated hydrogen atoms and subsequent desorption of acid molecules. The fate of the hydrogen atoms was probed through a combination of static and dynamic ab initio modelling approaches, which predicted H2 generation with favourable energetics. A better understanding of the functionalisation and interaction mechanisms will aid the rational design of biocompatible cobalt nanoparticles for various applications.


Assuntos
Ácidos Carboxílicos/química , Cobalto/química , Nanopartículas Metálicas/química , Adsorção , Nanopartículas de Magnetita/química , Modelos Moleculares , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
12.
J Mater Chem B ; 9(24): 4963-4980, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34114575

RESUMO

(Maghemite/poly(d,l-lactide-co-glycolide))/chitosan (core/shell)/shell nanoparticles have been prepared reproducibly by nanoprecipitation solvent evaporation plus coacervation (production performance ≈ 45%, average size ≈ 325 nm). Transmission electron microscopy, energy dispersive X-ray spectroscopy, electrophoretic determinations, and X-ray diffraction patterns demonstrated the satisfactory embedment of iron oxide nanocores within the solid polymer matrix and the formation of an external shell of chitosan in the nanostructure. The adequate magnetic responsiveness of the nanocomposites was characterized in vitro by hysteresis cycle determinations and by visualization of the nanosystem under the influence of a 0.4 T permanent magnet. Safety and biocompatibility of the (core/shell)/shell particles were based on in vitro haemocompatibility studies and cytotoxicity tests against HFF-1 human foreskin fibroblasts and on ex vivo toxicity assessments on tissue samples from Balb/c mice. Transversal relaxivities, determined in vitro at a low magnetic field of 1.44 T, demonstrated their capability as T2 contrast agents for magnetic resonance imaging, being comparable to that of some iron oxide-based contrast agents. Heating properties were evaluated in a high frequency alternating electromagnetic gradient: a constant maximum temperature of ≈46 °C was generated within ≈50 min, while antitumour hyperthermia tests on T-84 colonic adenocarcinoma cells proved the relevant decrease in cell viability (to ≈ 39%) when treated with the nanosystem under the influence of that electromagnetic field. Finally, in vivo magnetic resonance imaging studies and ex vivo histology determinations of iron deposits postulated the efficacy of chitosan to provide long-circulating capabilities to the nanocomposites, retarding nanoparticle recognition by the mononuclear phagocyte system. To our knowledge, this is the first study describing such a type of biocompatible and long-circulating nanoplatform with promising theranostic applications (biomedical imaging and hyperthermia) against cancer.


Assuntos
Quitosana/química , Engenharia , Hipertermia Induzida , Nanopartículas de Magnetita/química , Nanocompostos/química , Neoplasias/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanocompostos/uso terapêutico
13.
ACS Appl Mater Interfaces ; 13(24): 27814-27824, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34102839

RESUMO

Early spontaneous detection of thrombin activation benefits precise theranostics for thrombotic vascular disease. Herein, a thrombin-responsive nanoprobe conjugated by a FITC dye, PEGylated Fe3O4 nanoparticles, and a thrombin-sensitive peptide (LASG) was constructed to visualize thrombin activation and subsequent thrombosis in vivo. The FITC dye was linked to the LASG coated on the Fe3O4 nanoparticles for sensing the thrombin activity via the Förster resonance energy transfer effect. In vitro fluorescence imaging showed that the fluorescence signal intensity increased significantly after incubation with thrombin in contrast to that of the control group (p < 0.05), and the signal intensity was enhanced with the increase in thrombin concentration. Further in vivo fluorescence imaging also revealed that the signal elevated markedly in the left common carotid artery (LCCA) lesion of the mice thrombosis model after nanoprobe injection, in contrast to that of the control + nanoprobe group (p < 0.05). Moreover, the thrombin inhibitor bivalirudin could decrease the filling defect of the LCCA. Three-dimensional fusion images of micro-CT and fluorescence confirmed that filling defects in the LCCA were nicely colocalized with fluorescence signal caused by nanoprobes. The nanoplatform based on a thrombin-activatable visualization system could provide smart responsive and dynamic imaging of thrombosis in vivo.


Assuntos
Nanopartículas de Magnetita/química , Trombose/diagnóstico por imagem , Trombose/metabolismo , Sequência de Aminoácidos , Animais , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/química , Imageamento por Ressonância Magnética , Masculino , Camundongos , Microscopia Confocal , Microscopia de Fluorescência , Imagem Multimodal , Peptídeos/química , Trombose/patologia , Tomografia Computadorizada por Raios X
14.
ACS Appl Mater Interfaces ; 13(24): 27806-27813, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34105346

RESUMO

Cancer metastasis is still a major obstacle in clinical cancer therapy and a paramount cause of cancer deaths. Designing multifunctional nanoplatforms with an enhanced diagnostic sensitivity and anti-metastasis efficiency against tumors represents a major trend in current cancer management. Herein, we report the preparation of low-molecular-weight poly(ethylenimine) (PEI)-poly(ethylene glycol) (PEG) nanogels (NGs) loaded with transforming growth factor-ß1 (TGF-ß1) siRNA and ultrasmall iron oxide nanoparticles (Fe3O4 NPs) for gene therapy and T1-weighted magnetic resonance (MR) imaging of tumors and tumor metastasis in a mouse sarcoma model. In this work, ultrasmall Fe3O4 NPs stabilized by sodium citrate were first prepared and then mixed with PEI (800 Da) and PEG (400 Da)-diacrylate as a cross-linker to form Fe3O4/PEI-PEG NGs with an average size of 76.3 nm via an inverse microemulsion method. The developed hybrid NGs display good cytocompatibility and enhanced MR imaging performance (r1 relaxivity = 1.0346 mM-1 s-1). The Fe3O4/PEI-PEG NGs can be further used to compact TGF-ß1 siRNA through electrostatic interaction and efficiently deliver siRNA to cancer cells and a tumor model to silence the TGF-ß1 gene, which inhibits the growth and invasion of cancer cell in vitro significantly, as well as the growth of a subcutaneous sarcoma tumor model and lung metastasis in vivo. The designed hybrid NG-ultrasmall iron oxide NPs may be extended for the delivery of other drugs or genes for theranostics of different biological systems.


Assuntos
Portadores de Fármacos/química , Nanopartículas de Magnetita/química , Nanogéis/química , Polietilenoimina/química , RNA Interferente Pequeno/uso terapêutico , Sarcoma/terapia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inativação Gênica , Técnicas de Transferência de Genes , Terapia Genética , Imageamento por Ressonância Magnética , Camundongos , Peso Molecular , Fator de Crescimento Transformador beta1/genética
15.
Methods Mol Biol ; 2275: 265-277, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34118043

RESUMO

Multifunctional nanoplatforms are promising scaffolds for biomedical applications such as bioimaging, chemical/biological sensors, drug delivery, and cancer diagnosis and/or treatments. Mitochondria play crucial roles in metabolism of eukaryotic cells; therefore, mitochondria-targeting molecule such as triphenylphosphonium (TPP) is attached onto the magnetic mesoporous silica nanoparticle (Fe3O4@mSiO2). In order to track the nanoparticles, fluorescent carbon quantum dots (CDs) were conjugated to the Fe3O4@mSiO2. The as-constructed Fe3O4@mSiO2-TPP/CQD nanoplatform showed minimal cytotoxicity in various cell lines such as A549, CHO, HeLa, SH-SY5Y, HFF, and HMEC-1. External magnetic field-assisted uptake of the nanoplatform by tumor cell has been achieved promptly. More importantly, conjugation with CQDs endows the nanoplatform multicolored fluorescence that can remain bright and stable inside cells for a long time. This nanoplatform provides a multifunctional platform in targeting, imaging, and agent delivery for mitochondria-related disease diagnosis and treatment.


Assuntos
Carbono/química , Nanopartículas de Magnetita/química , Mitocôndrias/metabolismo , Neoplasias/diagnóstico por imagem , Dióxido de Silício/química , Células A549 , Animais , Células CHO , Linhagem Celular Tumoral , Cricetulus , Diagnóstico por Imagem , Corantes Fluorescentes/química , Células HeLa , Humanos , Neoplasias/metabolismo , Pontos Quânticos
16.
ACS Appl Mater Interfaces ; 13(23): 26782-26789, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34077176

RESUMO

Technologies for rapid screening of multiple foodborne pathogens have been urgently needed because of the complex food matrix and high outbreaks of foodborne diseases. In this study, multicolor coding up-conversion nanoparticles (UCNPs) were synthesized and applied for rapid and simultaneous detection of five kinds of foodborne pathogens. The multicolor coding UCNPs were obtained through doping different concentrations of a sensitizer (Yb3+) on the shell of the synthesized NaYF4:Yb3+, Tm3+ (20%/2%)@NaYF4:Yb3+, and Er3+ (x %/2%) core/shell nanocrystals. All the UCNPs could emit red and green luminescence simultaneously once excited with near-infrared wavelength (980 nm), and the ratio of red and green (R/G ratio) emission light intensity of each kind of UCNPs varied depending on the Yb3+ doping concentration. In addition, the magnetic nanoparticles (MNPs) modified with the monoclonal antibodies (mAbs) against the target bacteria were used to capture and separate the bacteria, resulting in obtaining the MNP-bacterium complexes. Different UCNPs with multicolor coding acted as signal probes were also modified with the mAbs to react with the MNP-bacterium complexes to form the MNP-bacterium-UCNP sandwich complexes. After the sandwich complexes were excited with a wavelength of 980 nm, the obtained R/G ratios and the green photoluminescence intensity (PL intensity) could be used to distinguish and quantitatively detect foodborne pathogens, respectively. This proposed nanoplatform could detect five foodborne pathogens simultaneously within 2 h with good sensitivity and specificity, showing great potential for multiplex detection of other targets in the fields of medical diagnosis and food security.


Assuntos
Anticorpos Monoclonais/imunologia , Bactérias/patogenicidade , Doenças Transmitidas por Alimentos/diagnóstico , Luminescência , Nanopartículas de Magnetita/química , Bactérias/classificação , Bactérias/imunologia , Doenças Transmitidas por Alimentos/microbiologia , Medições Luminescentes
17.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068597

RESUMO

Research on nanomaterial exposure-related health risks is still quite limited; this includes standardizing methods for measuring metals in living organisms. Thus, this study validated an atomic absorption spectrophotometry method to determine fertility and bioaccumulated iron content in Drosophila melanogaster flies after feeding them magnetite nanoparticles (Fe3O4NPs) dosed in a culture medium (100, 250, 500, and 1000 mg kg-1). Some NPs were also coated with chitosan to compare iron assimilation. Considering both accuracy and precision, results showed the method was optimal for concentrations greater than 20 mg L-1. Recovery values were considered optimum within the 95-105% range. Regarding fertility, offspring for each coated and non-coated NPs concentration decreased in relation to the control group. Flies exposed to 100 mg L-1 of coated NPs presented the lowest fertility level and highest bioaccumulation factor. Despite an association between iron bioaccumulation and NPs concentration, the 500 mg L-1 dose of coated and non-coated NPs showed similar iron concentrations to those of the control group. Thus, Drosophila flies' fertility decreased after NPs exposure, while iron bioaccumulation was related to NPs concentration and coating. We determined this method can overcome sample limitations and biological matrix-associated heterogeneity, thus allowing for bioaccumulated iron detection regardless of exposure to coated or non-coated magnetite NPs, meaning this protocol could be applicable with any type of iron NPs.


Assuntos
Drosophila melanogaster/fisiologia , Comportamento Alimentar , Ferro/metabolismo , Nanopartículas de Magnetita/química , Animais , Bioacumulação , Quitosana/química , Fertilidade , Limite de Detecção , Nanopartículas de Magnetita/ultraestrutura , Eletricidade Estática , Difração de Raios X
18.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068706

RESUMO

Enzymes have been exploited by humans for thousands of years in brewing and baking, but it is only recently that biocatalysis has become a mainstream technology for synthesis. Today, enzymes are used extensively in the manufacturing of pharmaceuticals, food, fine chemicals, flavors, fragrances and other products. Enzyme immobilization technology has also developed in parallel as a means of increasing enzyme performance and reducing process costs. The aim of this review is to present and discuss some of the more recent promising technical developments in enzyme immobilization, including the supports used, methods of fabrication, and their application in synthesis. The review highlights new support technologies such as the use of well-established polysaccharides in novel ways, the use of magnetic particles, DNA, renewable materials and hybrid organic-inorganic supports. The review also addresses how immobilization is being integrated into developing biocatalytic technology, for example in flow biocatalysis, the use of 3D printing and multi-enzymatic cascade reactions.


Assuntos
Biocatálise , Enzimas Imobilizadas/metabolismo , Nanopartículas de Magnetita/química , Estruturas Metalorgânicas/química , Impressão Tridimensional , Engenharia de Proteínas
19.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073072

RESUMO

Understanding the mechanism of interactions between magnetite nanoparticles and phospholipids that form cellular membranes at the molecular level is of crucial importance for their safe and effective application in medicine (e.g. magnetic resonance imaging, targeted drug delivery, and hyperthermia-based anticancer therapy). In these interactions, their surface coating plays a crucial role because even a small modification to its structure can cause significant changes to the behaviour of the magnetite nanoparticles that come in contact with a biomembrane. In this work, the influence of the magnetite nanoparticles functionalized with native and aminated starch on the thermodynamics, morphology, and dilatational elasticity of the model cell membranes was studied. The model cell membranes constituted the Langmuir monolayers formed at the air-water interface of dipalmitoylphosphatidylcholine (DPPC). The surface of the aminated starch-coated nanoparticles was enriched in highly reactive amino groups, which allowed more effective binding of drugs and biomolecules suitable for specific nano-bio applications. The studies indicated that the presence of these groups also reduced to some extent the disruptive effect of the magnetite nanoparticles on the model membranes and improved their adsorption.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Nanopartículas de Magnetita/química , Membranas Artificiais , Amido/química , Aminação , Propriedades de Superfície , Termodinâmica
20.
Theranostics ; 11(14): 6860-6872, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093858

RESUMO

Background: Immunotherapy has profoundly changed the landscape of cancer management and represented the most significant breakthrough. Yet, it is a formidable challenge that the majority of cancers - the so-called "cold" tumors - poorly respond to immunotherapy. To find a general immunoregulatory modality that can be applied to a broad spectrum of cancers is an urgent need. Methods: Magnetic hyperthermia (MHT) possesses promise in cancer therapy. We develop a safe and effective therapeutic strategy by using magnetism-mediated targeting MHT-immunotherapy in "cold" colon cancer. A magnetic liposomal system modified with cell-penetrating TAT peptide was developed for targeted delivery of a CSF1R inhibitor (BLZ945), which can block the CSF1-CSF1R pathway and reduce M2 macrophages. The targeted delivery strategy is characterized by its magnetic navigation and TAT-promoting intratumoral penetration. Results: The liposomes (termed TAT-BLZmlips) can induce ICD and cause excessive CRT exposure on the cell surface, which transmits an "eat-me" signal to DCs to elicit immunity. The combination of MHT and BLZ945 can repolarize M2 macrophages in the tumor microenvironment to relieve immunosuppression, normalize the tumor blood vessels, and promote T-lymphocyte infiltration. The antitumor effector CD8+ T cells were increased after treatment. Conclusion: This work demonstrated that TAT-BLZmlips with magnetic navigation and MHT can remodel tumor microenvironment and activate immune responses and memory, thus inhibiting tumor growth and recurrence.


Assuntos
Neoplasias do Colo/terapia , Terapia Combinada/métodos , Hipertermia , Imunoterapia/métodos , Lipossomos/química , Terapia de Campo Magnético/métodos , Nanopartículas de Magnetita/química , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Benzotiazóis/farmacocinética , Benzotiazóis/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/imunologia , Feminino , Humanos , Lipossomos/metabolismo , Lipossomos/efeitos da radiação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/terapia , Ácidos Picolínicos/farmacocinética , Ácidos Picolínicos/farmacologia , Ratos , Microambiente Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...