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181 0 _ai
182 0 _ab
200 1 _aSmart Design of a pH-Responsive System Based on pHLIP-Modified Magnetite Nanoparticles for Tumor MRI
_fA. M. Demin, A. G. Pershina, A. S. Minin [et al.]
203 _aText
_celectronic
300 _aTitle screen
330 _aMagnetic 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.
333 _aРежим доступа: по договору с организацией-держателем ресурса
461 _tACS Applied Materials and Interfaces
463 _tVol. 13, iss. 31
_v[P. 36800–36815]
_d2021
610 1 _aэлектронный ресурс
610 1 _aтруды учёных ТПУ
610 1 _amagnetic nanoparticles
610 1 _aFe3O4
610 1 _apHLIP
610 1 _atumor
610 1 _apH-triggered delivery
610 1 _aMRI
610 1 _aмагнитные наночастицы
610 1 _aопухоли
701 1 _aDemin
_bA. M.
_gAleksandr Mikhaylovich
701 1 _aPershina
_bA. G.
_cbiologist
_cAssociate Professor of Tomsk Polytechnic University, Candidate of biological sciences
_f1981-
_gAleksandra Gennadievna
_2stltpush
_3(RuTPU)RU\TPU\pers\32466
701 1 _aMinin
_bA. S.
_gArtem Sergeevich
701 1 _aBrikunova
_bO. Ya.
_gOlga Yaroslavovna
701 1 _aMurzakhaev
_bA. M.
_gAydar Marksovich
701 1 _aPerekucha
_bN. A.
_gNataljya Andreevna
701 1 _aRomashchenko
_bA. V.
_gAleksandr Vladimirovich
701 1 _aShevelev
_bO. B.
_gOleg Borisovich
701 1 _aUymin
_bM. A.
_gMikhail Aleksandrovich
701 1 _aByzov
_bI. V.
_gIljya Vladimrovich
701 1 _aMalkeeva
_bD.
_gDina
701 1 _aKiseleva
_bE. V.
_gElena Vladimirovna
701 1 _aEfimova
_bE. V.
_gElena Viktorovna
701 1 _aVtorushin
_bS. V.
_gSergey Vladimirovich
701 1 _aOgorodova
_bL. M.
_gLyudmila Mikhaylovna
712 0 2 _aНациональный исследовательский Томский политехнический университет
_bИсследовательская школа химических и биомедицинских технологий
_c(2017- )
_h8120
_2stltpush
_3(RuTPU)RU\TPU\col\23537
801 2 _aRU
_b63413507
_c20220513
_gRCR
856 4 _uhttps://doi.org/10.1021/acsami.1c07748
942 _cCF