Margaret Gradova

Dr. Margaret Gradova

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Research Focus & Metrics

Academic Career Length

14Years (2013-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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ISInga O. Savelyeva
Inga O. Savelyeva
KZKseniya A. Zhdanova
Kseniya A. Zhdanova
MGMargaret Gradova
Margaret Gradova
Oleg V. GradovOleg V. Gradov
Oleg V. Gradov
NBNatal’ya A. Bragina
Natal’ya A. Bragina
Antimicrobial photodynamic therapy (APDT) has received a great deal of attention due to its unique ability to kill all currently known classes of microorganisms. To date, infectious diseases caused by bacteria and viruses are one of the main sources of high mortality, mass epidemics and global pandemics among humans. Every year, the emergence of three to four previously unknown species of viruses dangerous to humans is recorded, totaling more than 2/3 of all newly discovered human pathogens. The emergence of bacteria with multidrug resistance leads to the rapid obsolescence of antibiotics and the need to create new types of antibiotics. From this point of view, photodynamic inactivation of viruses and bacteria is of particular interest. This review summarizes the most relevant mechanisms of antiviral and antibacterial action of APDT, molecular targets and correlation between the structure of cationic porphyrins and their photodynamic activity.

1 November 2022 in Russian Chemical Reviews
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VKValentin Kochervinskii
Valentin Kochervinskii
Oleg V. GradovOleg V. Gradov
Oleg V. Gradov
MGMargaret Gradova
Margaret Gradova
Highly polar fluorine-containing ferroelectric polymers based on vinylidene fluoride refer to the class of electroactive polymers suitable for various engineering applications. Under usual crystallization conditions, polycrystalline texture is formed, while after high-voltage polarization, it is transformed into a non-centrosymmetric structure, which gives rise to high piezoelectric and pyroelectric responses. Such materials can be used for pyroelectric energy conversion. Owing to high impact strength, ferroelectric polymers can serve as materials for alternative energy sources that convert dynamic impact energy into electricity. The non-linearity of electric response (owing to ferroelectricity) and high breakdown fields offer opportunity of using them in capacitive charge storage devices. The intense dynamics of the amorphous phase provides a rapid discharge of the stored energy into an external circuit. In view of the considerable fraction of the amorphous phase ( 50%) in fluorine-containing ferroelectric polymers and high dielectric permittivity of the amorphous phase, it is possible to change the system entropy by applying an electric field. In the case of pulsed field, this provides a temperature drop; therefore, these materials (especially as composites) are promising for the design of solid-state refrigerators. The high thermoplasticity of these polymers is useful for the design of sensors e.g., microphones) with a patterned active membrane surface and enhanced characteristics. Biocompatibility and low acoustic impedance (close to the impedance of biological tissues) accounts for the possibility of using these polymers as biosensors. When domains are present in a ferroelectric film, strong local electric fields appear, which can affect the activity of living cells. Using the direct and reverse piezoelectric effect, it is possible to stimulate and control the functions of various tissues, including the nervous tissue. The bibliography includes 463 references.

19 April 2023 in Pharmaceutics
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YBYuliya Bortnevskaya
Yuliya Bortnevskaya
NSNikita A. Shiryaev
Nikita A. Shiryaev
NZNikita Zakharov
Nikita Zakharov
OKOleg O. Kitoroage
Oleg O. Kitoroage
MGMargaret Gradova
Margaret Gradova
KZKseniya A. Zhdanova
Kseniya A. Zhdanova
Photodynamic therapy (PDT) in oncology is characterized by low invasiveness, minimal side effects, and little tissue scarring. Increasing the selectivity of PDT agents toward a cellular target is a new approach intended to improve this method. This study is devoted to the design and synthesis of a new conjugate based on meso-arylporphyrin with a low-molecular-weight tyrosine kinase inhibitor, Erlotinib. A nano-formulation based on Pluronic F127 micelles was obtained and characterized. The photophysical and photochemical properties and biological activity of the studied compounds and their nano-formulation were studied. A significant, 20–40-fold difference between the dark and photoinduced activity was achieved for the conjugate nanomicelles. After irradiation, the studied conjugate nanomicelles were 1.8 times more toxic toward the EGFR-overexpressing cell line MDA-MB-231 compared to the conditionally normal NKE cells. The IC50 was 0.073 ± 0.014 μM for the MDA-MB-231 cell line and 0.13 ± 0.018 μM for NKE cells after irradiation for the target conjugate nanomicelles.

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MGMargaret Gradova
Margaret Gradova
Oleg V. GradovOleg V. Gradov
Oleg V. Gradov
ALAnton Lobanov
Anton Lobanov
ABAnna Bychkova
Anna Bychkova
Elena Dmitrievna NikolskayaElena Dmitrievna Nikolskaya
Elena Dmitrievna Nikolskaya
DBDmitry Belykh
Dmitry Belykh
A novel amphiphilic cationic chlorin e6 derivative was investigated as a promising photosensitizer for photodynamic therapy. Two cationic –N(CH3)3+ groups on the periphery of the macrocycle provide additional hydrophilization of the molecule and ensure its electrostatic binding to the mitochondrial membranes and bacterial cell walls. The presence of a hydrophobic phytol residue in the same molecule results in its increased affinity towards the phospholipid membranes while decreasing its stability towards aggregation in aqueous media. In organic media, this chlorin e6 derivative is characterized by a singlet oxygen quantum yield of 55%. Solubilization studies in different polymer- and surfactant-based supramolecular systems revealed the effective stabilization of this compound in a photoactive monomolecular form in micellar nonionic surfactant solutions, including Tween-80 and Cremophor EL. A novel cationic chlorin e6 derivative also demonstrates effective binding towards serum albumin, which enhances its bioavailability and promotes effective accumulation within the target tissues. Laser confocal scanning microscopy demonstrates the rapid intracellular accumulation and distribution of this compound throughout the cells. Together with low dark toxicity and a rather good photostability, this compound demonstrates significant phototoxicity against HeLa cells causing cellular damage most likely through reactive oxygen species generation. These results demonstrate a high potential of this derivative for application in photodynamic therapy.

12 January 2023 in Pharmaceutics
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KZKseniya A. Zhdanova
Kseniya A. Zhdanova
AIAnastasia V. Ivantsova
Anastasia V. Ivantsova
FVFedor Yu. Vyalba
Fedor Yu. Vyalba
MUMaksim Usachev
Maksim Usachev
MGMargaret Gradova
Margaret Gradova
NBNatal’ya A. Bragina
Natal’ya A. Bragina
This paper reports on the design and synthesis of new multifunctional porphyrin-based therapeutic agents for potential therapeutic and diagnostic applications. Zinc complexes of A3B-type meso-arylporphyrins containing OH- and COOH- groups were modified with chelating ligands based on 4′-(4-methylphenyl)-2,2′:6′,2″-terpyridine derivatives in high yields. Novel complexes with Gd(III), Fe(III) were obtained for these conjugates. Aggregation behaviour in solutions of different solubilisers was studied to inform the selection of the optimal solubilising platform for the porphyrins obtained; their photophysical and photochemical properties were also characterised. Micellar Pluronic F127 formulation was found to be the most effective solubiliser for stabilising the fluorescence-active monomolecular form of the photosensitisers (PS). In vitro cytotoxicity of the compounds was studied on the HEP-2 cell line with and without irradiation for 1.5 and 24 h. As a result, the IC50 of compounds 12 and 14 at an irradiation dose of 8.073 J/cm2 was shown to be 1.87 ± 0.333 and 1.4 ± 0.152 μM, respectively; without irradiation, the compound had no toxic effect within the studied concentration range (1.5 h). A test for the inhibition of metabolic cooperation or promoter activity was also performed for the abovementioned compounds, showing the efficacy and safety of the conjugates obtained. Preliminary data have indicated the high potential of the new type of PS to be promising molecular theranostic agents.

1 April 2015 in Russian Chemical Bulletin
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MGMargaret Gradova
Margaret Gradova
KZKseniya A. Zhdanova
Kseniya A. Zhdanova
NBN. A. Bragina
N. A. Bragina
ALAnton Lobanov
Anton Lobanov
MMMikhail Melnikov
Mikhail Melnikov