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1.
Int J Mol Sci ; 24(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37569552

RESUMO

Novel magnetic nanocomposite materials based on Fe3O4 nanoparticles coated with iron and silica glycerolates (MNP@Fe(III)Glyc and MNP@Fe(III)/SiGlyc) were obtained. The synthesized nanocomposites were characterized using TEM, XRD, TGA, VMS, Mössbauer and IR spectroscopy. The amount of iron and silica glycerolates in the nanocomposites was calculated from the Mössbauer spectroscopy, ICP AES and C,H-elemental analysis. Thus, it has been shown that the distribution of Fe in the shell and core for MNP@Fe(III)Glyc and MNP@Fe(III)/SiGlyc is 27:73 and 32:68, respectively. The synthesized nanocomposites had high specific magnetization values and a high magnetic response to the alternating magnetic field. The hydrolysis of shells based on Fe(III)Glyc and Fe(III)/SiGlyc in aqueous media has been studied. It has been demonstrated that, while the iron glycerolates shell of MNP@Fe(III)Glyc is resistant to hydrolysis, the silica glycerolates shell of MNP@Fe(III)/SiGlyc is rather labile and hydrolyzed by 76.4% in 24 h at 25 °C. The synthesized materials did not show cytotoxicity in in vitro experiments (MTT-assay). The data obtained can be used in the design of materials for controlled-release drug delivery.

2.
Colloids Surf B Biointerfaces ; 221: 112981, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36343480

RESUMO

The architecture of a nanoparticles' surface formed due to a modification with a ligand and protein corona formation in biofluids is critical for interactions with cells in vivo. Here we studied interactions of immune cells with magnetic nanoparticles (MNPs) covalently modified with polyethylene glycol (PEG) and their counterparts conjugated with peptides: a pH (low) insertion peptide (pHLIP) and cycloRGD as a targeting ligand in human serum. The conjugation of MNPs-PEG with pHLIP, but not with cycloRGD, enhanced the association of these particles with mononuclear phagocytic cells in vitro and in vivo. We did not find a clear difference in protein corona composition between the pHLIP-modified and parental PEGylated nanoparticles. Analysis of the effect of autologous human serum on MNP uptake by monocytes showed that the efficiency of endocytosis varies among healthy donors and depends on intrinsic properties of serum. Nevertheless, using classic blood, coagulation, biochemical tests, and anti-PEG IgG serum level, we failed to identify the cause of the observed interdonor variation. These individual differences should be taken into consideration during testing of nanotherapeutics.


Assuntos
Nanopartículas , Coroa de Proteína , Humanos , Ligantes , Nanopartículas/química , Polietilenoglicóis/química , Peptídeos
3.
Pharmaceutics ; 14(11)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36365090

RESUMO

A series of new composite materials based on Fe3O4 magnetic nanoparticles coated with SiO2 (or aminated SiO2) were synthesized. It has been shown that the use of N-(phosphonomethyl)iminodiacetic acid (PMIDA) to stabilize nanoparticles before silanization ensures the increased content of a SiO2 phase in the Fe3O4@SiO2 nanocomposites (NCs) in comparison with materials obtained under similar conditions, but without PMIDA. It has been demonstrated for the first time that the presence of PMIDA on the surface of NCs increases the level of Dox loading due to specific binding, while surface modification with 3-aminopropylsilane, on the contrary, significantly reduces the sorption capacity of materials. These regularities were in accordance with the results of quantum chemical calculations. It has been shown that the energies of Dox binding to the functional groups of NCs are in good agreement with the experimental data on the Dox sorption on these NCs. The mechanisms of Dox binding to the surface of NCs were proposed: simultaneous coordination of Dox on the PMIDA molecule and silanol groups at the NC surface leads to a synergistic effect in Dox binding. The synthesized NCs exhibited pH-dependent Dox release, as well as dose-dependent cytotoxicity in in vitro experiments. The cytotoxic effects of the studied materials correspond to their calculated IC50 values. NCs with a SiO2 shell obtained using PMIDA exhibited the highest effect. At the same time, the presence of PMIDA in NCs makes it possible to increase the Dox loading, as well as to reduce its desorption rate, which may be useful in the design of drug delivery vehicles with a prolonged action. We believe that the data obtained can be further used to develop stimuli-responsive materials for targeted cancer chemotherapy.

4.
Int J Mol Sci ; 23(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36012356

RESUMO

Novel nanocomposite materials based on Fe3O4 magnetic nanoparticles (MNPs) coated with silica and covalently modified by [(3-triethoxysilyl)propyl]succinic acid-polyethylene glycol (PEG 3000) conjugate, which provides a high level of doxorubicin (Dox) loading, were obtained. The efficiency of Dox desorption from the surface of nanomaterials under the action of an alternating magnetic field (AMF) in acidic and neutral media was evaluated. Their high cytotoxicity against tumor cells, as well as the drug release upon application of AMF, which leads to an increase in the cytotoxic effect, was demonstrated.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Linhagem Celular , Doxorrubicina/farmacologia , Portadores de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Fenômenos Magnéticos , Polietilenoglicóis , Dióxido de Silício
5.
Materials (Basel) ; 15(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897559

RESUMO

The magnetic and microwave properties of nanocomposites containing iron particles encapsulated in a carbon shell (Fe@C), as well as carbon nanotubes (CNT), have been experimentally studied. The examination of magnetic properties of composites shows that the materials under study contain a ferromagnetic component. The availability of ferromagnetic ordering for the dielectric matrix-based nanocomposite sample with Fe@C particles has been confirmed by the measurement results of the transmission and the reflection coefficients of the microwaves, since the ferromagnetic resonance has been observed. Furthermore, in the fields less than the field of ferromagnetic resonance, there are the signs of the presence of ferromagnetic antiresonance. The ferromagnetic resonance leads to minima in the transmission and reflection coefficients, whereas the antiresonance, conversely, leads to maxima in the reflection coefficient. The measurement results have been compared with the theoretical calculations of the field dependence of microwave transmission and reflection coefficients.

6.
ACS Appl Mater Interfaces ; 13(31): 36800-36815, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34324807

RESUMO

Magnetic Fe3O4 nanoparticles (MNPs) are often used to design agents enhancing contrast in magnetic resonance imaging (MRI) that can be considered as one of the efficient methods for cancer diagnostics. At present, increasing the specificity of the MRI contrast agent accumulation in tumor tissues remains an open question and attracts the attention of a wide range of researchers. One of the modern methods for enhancing the efficiency of contrast agents is the use of molecules for tumor acidic microenvironment targeting, for example, pH-low insertion peptide (pHLIP). We designed novel organosilicon MNPs covered with poly(ethylene glycol) (PEG) and covalently modified by pHLIP. To study the specific features of the binding of pHLIP-modified MNPs to cells, we also obtained nanoconjugates with Cy5 fluorescent dye embedded in the SiO2 shell. The nanoconjugates obtained were characterized by transmission electron microscopy (TEM), attenuated total reflection (ATR), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), dynamic light scattering (DLS), UV and fluorescence spectrometry, thermogravimetric analysis (TGA), CHN elemental analyses, and vibrating sample magnetometry. Low cytotoxicity and high specificity of cellular uptake of pHLIP-modified MNPs at pH 6.4 versus 7.4 (up to 23-fold) were demonstrated in vitro. The dynamics of the nanoconjugate accumulation in the 4T1 breast cancer orthotopically grown in BALB/c mice and MDA-MB231 xenografts was evaluated in MRI experiments. Biodistribution and biocompatibility studies of the obtained nanoconjugate showed no pathological change in organs and in the blood biochemical parameters of mice after MNP administration. A high accumulation rate of pHLIP-modified MNPs in tumor compared with PEGylated MNPs after their intravenous administration was demonstrated. Thus, we propose a promising approach to design an MRI agent with the tumor acidic microenvironment targeting ability.


Assuntos
Meios de Contraste/química , Proteínas Imobilizadas/química , Nanopartículas de Magnetita/química , Neoplasias/diagnóstico por imagem , Peptídeos/química , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Meios de Contraste/toxicidade , Feminino , Humanos , Concentração de Íons de Hidrogênio , Proteínas Imobilizadas/toxicidade , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/toxicidade , Camundongos Endogâmicos BALB C , Peptídeos/toxicidade , Dióxido de Silício/química , Dióxido de Silício/toxicidade
7.
Colloids Surf B Biointerfaces ; 190: 110879, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32135495

RESUMO

The efficiency of magnetic labeling with L-Lys-modified Fe3O4 magnetic nanoparticles (MNPs) and the stability of magnetization of rat adipose-derived mesenchymal stem cells, lineage-negative (Lin(-)) hematopoietic progenitor cells from mouse bone marrow and human leukemia K562 cells were studied. For this purpose, covalent modification of MNPs with 3-aminopropylsilane and N-di-Fmoc-L-lysine followed by removal of N-protecting groups was carried out. Since the degree of hydroxylation of the surface of the starting nanoparticles plays a crucial role in the silanization reaction and the possibility of obtaining stable colloidal solutions. In present work we for the first time performed a comparative qualitative and quantitative evaluation of the number of adsorbed water molecules and hydroxyl groups on the surface of chemically and physically obtained Fe3O4 MNPs using comprehensive FTIR spectroscopy and thermogravimetric analysis. The results obtained can be further used for magnetic labeling of cells in experiments in vitro and in vivo.


Assuntos
Compostos Férricos/química , Lisina/química , Nanopartículas de Magnetita/química , Animais , Células Cultivadas , Humanos , Células K562 , Fenômenos Magnéticos , Tamanho da Partícula , Ratos , Propriedades de Superfície
8.
Langmuir ; 34(11): 3449-3458, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29478322

RESUMO

The surface modification of Fe3O4-based magnetic nanoparticles (MNPs) with N-(phosphonomethyl)iminodiacetic acid (PMIDA) was studied, and the possibility of their use as magnetic resonance imaging contrast agents was shown. The effect of the added PMIDA amount, the reaction temperature and time on the degree of immobilization of this reagent on MNPs, and the hydrodynamic characteristics of their aqueous colloidal solutions have been systematically investigated for the first time. It has been shown that the optimum condition for the modification of MNPs is the reaction at 40 °C with an equimolar amount of PMIDA for 3.5 h. The modified MNPs were characterized by X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric, and CHN elemental analyses. The dependence of the hydrodynamic characteristics of the MNP colloidal solutions on the concentration and pH of the medium was studied by the dynamic light scattering method. On the basis of the obtained data, we can assume that the PMIDA molecules are fixed on the surface of the MNPs as a monomolecular layer. The modified MNPs had good colloidal stability and high magnetic properties. The calculated relaxivities r2 and r1 were 341 and 102 mmol-1 s-1, respectively. The possibility of using colloidal solutions of PMIDA-modified MNPs as a T2 contrast agent for liver studies in vivo (at a dose of 0.6 mg kg-1) was demonstrated for the first time.


Assuntos
Meios de Contraste/farmacologia , Fígado/metabolismo , Nanopartículas de Magnetita/química , Ácido Fosfonoacéticos/análogos & derivados , Animais , Células CHO , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/toxicidade , Cricetulus , Humanos , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/toxicidade , Masculino , Mesocricetus , Ácido Fosfonoacéticos/química , Ácido Fosfonoacéticos/farmacologia , Ácido Fosfonoacéticos/toxicidade , Temperatura
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