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  1. Article ; Online: Influence of Cucurbiturils on the Production of Reactive Oxygen Species by T- and B-Lymphocytes, Platelets and Red Blood Cells.

    Aktanova, Alina A / Boeva, Olga S / Barkovskaya, Margarita Sh / Kovalenko, Ekaterina A / Pashkina, Ekaterina A

    International journal of molecular sciences

    2023  Volume 24, Issue 2

    Abstract: Reactive oxygen species (ROS) are highly reactive chemical molecules containing oxygen. ROS play an important role in signaling and cell homeostasis at low and moderate concentrations. ROS could be a cause of damage to proteins, nucleic acids, lipids, ... ...

    Abstract Reactive oxygen species (ROS) are highly reactive chemical molecules containing oxygen. ROS play an important role in signaling and cell homeostasis at low and moderate concentrations. ROS could be a cause of damage to proteins, nucleic acids, lipids, membranes and organelles at high concentrations. There are a lot of cells that can produce ROS to maintain functional activity. It is known that metal nanoparticles can increase production of ROS in cells. However, the effect of cucurbiturils on ROS production is still unknown. In our study, we evaluated production of ROS by the immune (T-, B-lymphocytes, NK-cells) and non-immune cells (red blood cells, platelets), as well as tumor cells line (1301, K562) after treatment with cucurbiturils in vitro. Assessment of reactive oxide species (ROS) were provided by using dihydrorhodamine 123 (DHR 123). Fluorescence intensity and percentage DHR123 were measured by flow cytometry. Platelets, erythrocytes and activated T-helpers were changed the level of ROS production in response to stimulation with cucurbiturils. It was found that the percentage of these ROS-producing cells was reduced by cucurbiturils. Thus, cucurbiturils may affect the production of ROS by cells, but further research is needed in this area.
    MeSH term(s) Reactive Oxygen Species/metabolism ; Blood Platelets/metabolism ; Erythrocytes/metabolism ; B-Lymphocytes/metabolism
    Chemical Substances Reactive Oxygen Species
    Language English
    Publishing date 2023-01-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24021441
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Evaluation of the Immunosafety of Cucurbit[n]uril In Vivo.

    Pashkina, Ekaterina / Aktanova, Alina / Boeva, Olga / Bykova, Maria / Gavrilova, Elena / Goiman, Elena / Kovalenko, Ekaterina / Saleh, Na'il / Grishina, Lyubov / Kozlov, Vladimir

    Pharmaceutics

    2024  Volume 16, Issue 1

    Abstract: Cucurbiturils are a family of macrocyclic oligomers capable of forming host-guest complexes with various molecules. Due to noncovalent binding to drug molecules and low toxicity, cucurbiturils has been extensively investigated as potential carriers for ... ...

    Abstract Cucurbiturils are a family of macrocyclic oligomers capable of forming host-guest complexes with various molecules. Due to noncovalent binding to drug molecules and low toxicity, cucurbiturils has been extensively investigated as potential carriers for drug delivery. However, the immune system's interactions with different drug carriers, including cucurbiturils, are still under investigation. In this study, we focused on cucurbiturils' immunosafety and immunomodulation properties in vivo. We measured blood counts and lymphocyte subpopulations in blood, spleen, and bone marrow, and assessed the in vivo toxicity to spleen and bone marrow cells after intraperitoneal administration to BALB/c mice. When assessing the effect of cucurbit[6]uril on blood parameters after three intraperitoneal injections within a week in laboratory animals, a decrease in white blood cells was found in mice after injections of cucurbit[6]util, but the observed decrease in the number of white blood cells was within the normal range. At the same time, cucurbit[7]uril and cucurbit[8]uril did not affect the leukocyte counts of mice after three injections. Changes in the number of platelets, erythrocytes, and monocytes, as well as in several other indicators, such as hematocrit or erythrocyte volumetric dispersion, were not detected. We show that cucurbiturils do not have immunotoxicity in vivo, with the exception of a cytotoxic effect on spleen cells after сucurbit[7]uril administration at a high dosage. We also evaluated the effect of cucurbiturils on cellular and humoral immune responses. We founded that cucurbiturils in high concentrations affect the immune system in vivo, and the action of various cucurbiturils differs in different homologues, which is apparently associated with different interactions in the internal environment of the body.
    Language English
    Publishing date 2024-01-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics16010127
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Assessment of the Biocompatibility of Cucurbiturils in Blood Cells.

    Aktanova, Alina / Abramova, Tatjana / Pashkina, Ekaterina / Boeva, Olga / Grishina, Lyubov / Kovalenko, Ekaterina / Kozlov, Vladimir

    Nanomaterials (Basel, Switzerland)

    2021  Volume 11, Issue 6

    Abstract: Currently, cucurbiturils are being actively researched all over the world. Research is focused on the ways of improving the solubility and selectivity of cucurbiturils, increasing the stability of the complexes with other particles in various media and ... ...

    Abstract Currently, cucurbiturils are being actively researched all over the world. Research is focused on the ways of improving the solubility and selectivity of cucurbiturils, increasing the stability of the complexes with other particles in various media and enhancing their ability to bind and release various substances. The most significant area of our research is the assessment of safety, studying the biological properties and synergistic effects of cucurbiturils during complexation with drugs. In this article, the hemocompatibility of erythrocytes and leukocytes with cucurbiturils was investigated. We demonstrated that cucurbiturils have no cytotoxic effect, even at high concentrations (1 mM) and do not affect the viability of PBMCs. However, cucurbiturils can increase the level of the early apoptosis of lymphocytes and cucurbit[7]uril enhances hemolysis in biologically relevant media. Despite this, cucurbiturils are fairly safe organic molecules in concentrations up to 0.3 mM. Thus, we believe that it will become possible to use polymer nanostructures as drug delivery systems in clinical practice, since cucurbiturils can be modified to improve pharmacological properties.
    Language English
    Publishing date 2021-05-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano11061356
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy.

    Pashkina, Ekaterina / Evseenko, Veronika / Dumchenko, Natalya / Zelikman, Maxim / Aktanova, Alina / Bykova, Maria / Khvostov, Mikhail / Dushkin, Aleksandr / Kozlov, Vladimir

    Nanomaterials (Basel, Switzerland)

    2021  Volume 12, Issue 1

    Abstract: The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to ... ...

    Abstract The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. It is also known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, meaning that it could potentially enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of the supramolecular complexes (micelles) of GA with extracts of allergens holds promise for the development of new drugs for AIT.
    Language English
    Publishing date 2021-12-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano12010148
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Effect of Cucurbit[7]uril on the Antitumor and Immunomodulating Properties of Oxaliplatin and Carboplatin.

    Pashkina, Ekaterina / Aktanova, Alina / Mirzaeva, Irina / Kovalenko, Ekaterina / Andrienko, Irina / Knauer, Nadezhda / Pronkina, Natalya / Kozlov, Vladimir

    International journal of molecular sciences

    2021  Volume 22, Issue 14

    Abstract: Cucurbit[7]uril (CB[7]) is a molecular container that may form host-guest complexes with platinum(II) anticancer drugs and modulate their efficacy and safety. In this paper, we report our studies of the effect of CB[7]-oxaliplatin complex and the mixture ...

    Abstract Cucurbit[7]uril (CB[7]) is a molecular container that may form host-guest complexes with platinum(II) anticancer drugs and modulate their efficacy and safety. In this paper, we report our studies of the effect of CB[7]-oxaliplatin complex and the mixture of CB[7] and carboplatin (1:1) on viability and proliferation of a primary cell culture (peripheral blood mononuclear cells), two tumor cell lines (B16 and K562) and their activity in the animal model of melanoma. At the same time, we studied the impact of platinum (II) drugs with CB[7] on T cells and B cells in vitro. Although the stable CB[7]-carboplatin complex was not formed, the presence of cucurbit[7]uril affected the biological properties of carboplatin. In vivo, CB[7] increased the antitumor effect of carboplatin, but, at the same time, increased its acute toxicity. Compared to free oxaliplatin, its complex with CB[7] shows a greater cytotoxic effect on tumor cell lines B16 and K562, while in vivo, the effects of the free drug and encapsulated drug were comparable. However, in vivo studies also demonstrated that the encapsulation of oxaliplatin in CB[7] lowered the toxicity of the drug.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Bridged-Ring Compounds/pharmacology ; Carboplatin/pharmacology ; Female ; Humans ; Imidazoles/pharmacology ; Immunologic Factors/pharmacology ; K562 Cells ; Melanoma, Experimental/drug therapy ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Mice ; Organoplatinum Compounds/pharmacology ; Pyridines/pharmacology
    Chemical Substances Antineoplastic Agents ; Bridged-Ring Compounds ; Imidazoles ; Immunologic Factors ; Organoplatinum Compounds ; Pyridines ; cucurbit(7)uril ; oxiplatin ; Carboplatin (BG3F62OND5)
    Language English
    Publishing date 2021-07-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22147337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells.

    Knauer, Nadezhda / Pashkina, Ekaterina / Aktanova, Alina / Boeva, Olga / Arkhipova, Valeria / Barkovskaya, Margarita / Meschaninova, Mariya / Karpus, Andrii / Majoral, Jean-Pierre / Kozlov, Vladimir / Apartsin, Evgeny

    Pharmaceutics

    2022  Volume 15, Issue 1

    Abstract: Short regulatory oligonucleotides are considered prospective tools for immunotherapy. However, they require an adequate carrier to deliver potential therapeutics into immune cells. Herein, we explore the potential of polycationic dendrimers as carriers ... ...

    Abstract Short regulatory oligonucleotides are considered prospective tools for immunotherapy. However, they require an adequate carrier to deliver potential therapeutics into immune cells. Herein, we explore the potential of polycationic dendrimers as carriers for microRNAs in peripheral blood mononuclear cells of healthy donors. As an oligonucleotide cargo, we use a synthetic mimic and an inhibitor of miR-155, an important factor in the development and functioning of immunocompetent cells. Dendrimers bind microRNAs into low-cytotoxic polyelectrolyte complexes that are efficiently uptaken by immunocompetent cells. We have shown these complexes to affect the number of T-regulatory cells, CD14
    Language English
    Publishing date 2022-12-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15010148
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  7. Article ; Online: Evaluation of the Immunosafety of Cucurbit[n]uril on Peripheral Blood Mononuclear Cells In Vitro.

    Pashkina, Ekaterina / Aktanova, Alina / Blinova, Elena / Mirzaeva, Irina / Kovalenko, Ekaterina / Knauer, Nadezhda / Ermakov, Aleksandr / Kozlov, Vladimir

    Molecules (Basel, Switzerland)

    2020  Volume 25, Issue 15

    Abstract: Cucurbiturils (CB[n]s) are nanoscale macrocyclic compounds capable of encapsulating a molecule or part of a molecule by forming host-guest complexes. Integration of drugs with CB[n] is used for the following purposes: controlling clearance; protection of ...

    Abstract Cucurbiturils (CB[n]s) are nanoscale macrocyclic compounds capable of encapsulating a molecule or part of a molecule by forming host-guest complexes. Integration of drugs with CB[n] is used for the following purposes: controlling clearance; protection of the drug from biodegradation; targeted delivery to specific organs, tissues, or cells; reduction of toxicity; and improving solubility. One of the major problems encountered in the application of new drug delivery systems is lack of knowledge of their biological properties. CB[n], unlike many other often toxic nanoparticles, has extremely low toxicity, even at high doses. However, many aspects of the biological actions of these nanoscale cavitands remain unclear, including the immunotropic properties. In this study, we investigated the immunotoxicity and immunomodulation properties of CB[n]. It was found that CB[7] and CB[6] did not decrease the viability of mononuclear cells at all tested concentrations from 0.1-1 mM. Overall, the results indicated an immunomodulatory effect of different concentrations of CB[n]. In the case of a longer cultivation time, CB[n] had an immunostimulating effect, which was indicated by an enhancement of the proliferative activity of cells and increased expression of HLA-DR on lymphocytes.
    MeSH term(s) Apoptosis/drug effects ; Cell Cycle/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Macrocyclic Compounds/adverse effects ; Macrocyclic Compounds/pharmacology
    Chemical Substances Macrocyclic Compounds ; cucurbit(n)uril
    Language English
    Publishing date 2020-07-27
    Publishing country Switzerland
    Document type Evaluation Study ; Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules25153388
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: pH-Sensitive Dendrimersomes of Hybrid Triazine-Carbosilane Dendritic Amphiphiles-Smart Vehicles for Drug Delivery.

    Apartsin, Evgeny / Knauer, Nadezhda / Arkhipova, Valeria / Pashkina, Ekaterina / Aktanova, Alina / Poletaeva, Julia / Sánchez-Nieves, Javier / de la Mata, Francisco Javier / Gómez, Rafael

    Nanomaterials (Basel, Switzerland)

    2020  Volume 10, Issue 10

    Abstract: Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a ... ...

    Abstract Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species-triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy.
    Language English
    Publishing date 2020-09-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662255-5
    ISSN 2079-4991
    ISSN 2079-4991
    DOI 10.3390/nano10101899
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