Institute of Biophysics and Cell Engineering

Background/Objectives: Current promising treatments for many diseases are based on the use of therapeutic nucleic acids, including DNA. However, the list of nanocarriers is limited due to their low biocompatibility, high cost, and toxicity. The design of synthetic building blocks for creating universal delivery systems for genetic material is an unsolved problem. In this work, we propose PAMAM dendrimers with rigid thiacalixarene core in various conformations, i.e., PAMAM-calix-dendrimers, as a platform for a supramolecular universal constructor for nanomedicine. Results: Third generation PAMAM dendrimers with a macrocyclic core in three conformations (cone, partial cone, and 1,3-alternate) were synthesized for the first time. The obtained dendrimers were capable of binding and compacting calf thymus DNA, whereby the binding efficiency improved with increasing generation, while the influence of the macrocyclic core was reduced. A dramatic effect of the macrocyclic core conformation on the hemolytic activity of PAMAM-calix-dendrimers was observed. Specifically, a notable reduction in hemotoxicity was associated with a decrease in compound amphiphilicity. Conclusions: We hope the results will help reduce financial and labor costs in developing new drug delivery systems based on dendrimers.

NanomedicineAhead of Print EditorialDendrimer-mediated gene delivery to boost cancer immunotherapyMengsi Zhan, Huxiao Sun, Joao Rodrigues, Dzmitry Shcharbin, Mingwu Shen & Xiangyang ShiMengsi ZhanState Key Laboratory for Modification of Chemical Fibers & Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials & Regenerative Medicine, College of Biological Science & Medical Engineering, Donghua University, Shanghai, 201620, People’s Republic of ChinaSearch for more papers by this author, Huxiao SunState Key Laboratory for Modification of Chemical Fibers & Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials & Regenerative Medicine, College of Biological Science & Medical Engineering, Donghua University, Shanghai, 201620, People’s Republic of ChinaSearch for more papers by this author, Joao RodriguesCQM – Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus Universitário da Penteada, 9020-105, Funchal, PortugalSearch for more papers by this author, Dzmitry ShcharbinInstitute of Biophysics & Cell Engineering of NASB, Akademicheskaya 27, 220072, Minsk, BelarusSearch for more papers by this author, Mingwu ShenState Key Laboratory for Modification of Chemical Fibers & Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials & Regenerative Medicine, College of Biological Science & Medical Engineering, Donghua University, Shanghai, 201620, People’s Republic of ChinaSearch for more papers by this author & Xiangyang Shi *Author for correspondence: Tel.: +86 216 779 2656; E-mail Address: xshi@dhu.edu.cnhttps://orcid.org/0000-0001-6785-6645State Key Laboratory for Modification of Chemical Fibers & Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials & Regenerative Medicine, College of Biological Science & Medical Engineering, Donghua University, Shanghai, 201620, People’s Republic of ChinaCQM – Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus Universitário da Penteada, 9020-105, Funchal, PortugalSearch for more papers by this authorPublished Online:31 May 2023https://doi.org/10.2217/nnm-2023-0124AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: gene deliveryimmunotherapyPAMAM dendrimerssiRNAtumor microenvironment

ABSTRACT T-cell activation through the blockade of PD-1/PD-L1 interaction by monoclonal antibodies has demonstrated the clinical benefit for patients with diverse types of metastatic cancers. However, a number of limitations when producing and using antibodies hamper their broader clinical application. This awakened a significant interest in design and discovery of small-molecule inhibitors (SMIs) of PD-1/PD-L1 interaction, and several such inhibitors have been identified. However, up to now, many mechanistic details of their inhibitory action remain not fully understood. In this work, a new protocol of enhanced protein conformational sampling combining RosettaLigand and Schrodinger Induced Fit Docking approaches with Molecular Dynamics simulations, preceded by structural modelling of the full-length PD-L1 – dimer in the heterogeneous environment including the membrane and extracellular solution, are used for the prediction of atomistic structures of the complexes of the PD-L1 dimers with BMS-1016, BMS-2007, BMS-4121, BMS-40210, four SMIs with a high inhibitory activity in vitro against PD-1/PD-L1 interaction. Critical protein–ligand interactions responsible for the stabilisation of the complexes of the PD-L1 dimer with SMIs and high inhibitory activities of these SMIs against the PD-1/PD-L1 interaction are revealed. The roles of the membrane and of interaction of PD-L1 with its cis and trans protein partners are also addressed.

An important place in the pathogenesis of systemic lupus erythematosus (SLE) is given to the immune mechanisms, many aspects of which, despite intensive study, remain unclear. As a result of the activation of T and B cells, the production of antibodies (including autoantibodies) increases, hypergammaglobulinemia occurs, and immune complexes are formed. The use of mesenchymal stem cells (MSCs) as the basis of a biomedical cell product for SLE cell therapy is justified due to the fact that this type of stem cells has a wide immunomodulatory activity range. In recent years, more and more data have appeared that the pooled cultures of allogeneic MSCs have more pronounced and stable immunomodulatory properties in relation to immunocompetent cells, in comparison with allogeneic MSCs obtained from a single donor.The aim of the study was to develop a biomedical cell product based on pooled cultures of MSCs to increase the effectiveness of the existing methods of treating SLE.The object of the study was the venous blood of SLE patients with clinical and laboratory lupus nephritis signs included in the trials (n = 6). Blood sampling and analysis were carried out before cell therapy and 1-1.5 months after. Immunophenotyping of blood cells was performed using flow cytometry.The immunological efficacy of SLE cell therapy, which was expressed in a decrease of the number of immunocompetent cells associated with the inflammation process in the peripheral blood (decrease in the content of cytotoxic lymphocytes, activated and terminally differentiated TEMRA T cells, decrease in the number of antibody-producing plasma cells) with the use of poolMSC was shown. Clinical efficacy consisted in stopping the progression and reducing the SLE activity (doubling the SELENA-SLEDAI index from 10.43 to 5.14), as well as in achieving the complete LN remission (n = 4) and restoring the normal kidney function.

Against the background of global climate change, drought stress has become one of the environmental limiting factors that can significantly influence the growth and development of crop plants. Drought stress conditions also cause changes in plant physiological and metabolic processes. The influence of soil drought on the mineral composition of the leaves of two Actinidia species with С3-type photosynthesis, namely, Actinidia argutа (Siebold & Zucc.) Planch. ex Miq. cultivar ‘Taezhny Dar’ and Actinidia kolomikta (Maxim. & Rupr.) Maxim. cultivar ‘Narodnaya’, was studied through energy dispersive spectrometry. The investigations were carried out during 2020 to 2021 at the Department of Genofonde and Bioresources of Plants, Federal Scientific Center for Horticulture, Moscow. The present research revealed that actinidia leaves contained the following major elements: K (11.19 mass% to 13.84 mass%), Ca (7.83% to 12.08 mass%), Cl (6.20 mass% to 7.33 mass%), and Mg (2.98 mass% to 3.44 mass%). Low values were recorded for Mo (1.19 mass% to 4.49 mass%) and P (0.83 mass% to 1.25 mass%). In both species, the mineral elements K and Ca were present at high levels. A positive correlation was observed between Mg–P, K–Mn, Mn–Se, Cu-Se, P–Si, Na–Mo, and Si–Mn in the leaves of A. argutа and between Cl–Ca, Mo; P–Si, Mo; and K–Ca in the leaves of A. kolomikta. Under stress conditions, the ratios of K/Ca and K/P declined to 0.9 and 6.3, respectively, whereas those of K/Cl, K/Mg, and K/Mo increased to 3.8, 4.4, and 2.7, respectively. The present studies confirmed that actinidia leaves contained high concentrations of minerals, especially K, Ca, P, and Mg, and that the accumulation of mineral elements in actinidia plant leaves under drought conditions varied depending on the species.

Abstract We assessed the content of some major and trace elements and lichen compounds as well as antioxidant activity in eight lichen species representing four families collected in areas > 1 km distant from Bellingshausen (King George Island) and > 1 km distant from Molodezhnaya (Thala Hills, Enderby Land) research stations. Content levels of Cu, Pb, Cd, Zn and As in Physcia caesia, Physconia muscigena, Umbilicaria aprina, Umbilicaria decussata and Usnea aurantiaco-atra thalli were similar to or lower than previously reported for these species in the Maritime and Continental Antarctic, as well as from reference sites. The first data on the contents of 15 elements in Ramalina terebrata and Thamnolecania brialmontii thalli from the Maritime Antarctic are reported. Our analyses confirmed the presence of the main photosynthetic pigments in the species examined (chlorophyll a and b, phaeophytin a and b, neoxanthin, violaxanthin, lutein and β-carotene). We identified protolichesterinic acid in T. brialmontii thalli for the first time. Antioxidant activity varied from 190 μg/g dry weight (U. decussata) to 14,740 μg/g dry weight (T. brialmontii). The data obtained complement previous research while also providing new baseline data that will have utility in monitoring and identifying future change.