Publications by authors named "Mikhail A Uimin"

3 Publications

  • Page 1 of 1

Smart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI.

ACS Appl Mater Interfaces 2021 Aug 29;13(31):36800-36815. Epub 2021 Jul 29.

Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 620108 Yekaterinburg, Russia.

Magnetic FeO 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 SiO 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.
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http://dx.doi.org/10.1021/acsami.1c07748DOI Listing
August 2021

L-Lysine-modified FeO nanoparticles for magnetic cell labeling.

Colloids Surf B Biointerfaces 2020 Jun 19;190:110879. Epub 2020 Feb 19.

Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 22 S. Kovalevskoy St., Yekaterinburg, 620990, Russia; Institute of Chemical Engineering, Ural Federal University, 19 Mira St., Yekaterinburg, 620002, Russia.

The efficiency of magnetic labeling with L-Lys-modified FeO 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 FeO 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.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110879DOI Listing
June 2020

PMIDA-Modified FeO Magnetic Nanoparticles: Synthesis and Application for Liver MRI.

Langmuir 2018 03 6;34(11):3449-3458. Epub 2018 Mar 6.

Siberian State Medical University , 2 Moskovsky Trakt , 634050 Tomsk , Russia.

The surface modification of FeO-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 r and r were 341 and 102 mmol s, respectively. The possibility of using colloidal solutions of PMIDA-modified MNPs as a T contrast agent for liver studies in vivo (at a dose of 0.6 mg kg) was demonstrated for the first time.
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http://dx.doi.org/10.1021/acs.langmuir.7b04023DOI Listing
March 2018
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