Magnetic particles with polymeric shells bearing cholesterol moieties sensitize breast cancer cells to low doses of doxorubicin

One of the promising strategies for improvement of cancer treatment is application of a combination therapy. The aim of this study was to investigate the anticancer activity of nanoformulations containing doxorubicin and iron oxide particles covered with polymeric shells bearing cholesterol moieties. It was postulated that due to high affinity to cell membranes, particles comprising poly(cholesteryl acrylate) can sensitize cancer cells to doxorubicin chemotherapy. The performed analyses revealed that the developed systems are effective against the human breast cancer cell lines MCF-7 and MDA-MB-231 even at low doses of the active compound applied (0.5 µM). Additionally, high compatibility and lack of toxicity of the tested materials against human red blood cells, immune (monocytic THP-1) cells, and cardiomyocyte H9C2(2-1) cells was demonstrated. Synergistic effects observed upon administration of doxorubicin with polymer–iron oxide hybrids comprising poly(cholesteryl acrylate) may provide an opportunity to limit toxicity of the drug and to improve its therapeutic efficiency at the same time

Membrane-Active Thermoresponsive Block Copolymers Containing a Diacylglycerol-Based Segment: RAFT Synthesis, Doxorubicin Encapsulation, and Evaluation of Cytotoxicity against Breast Cancer Cells

Herein, we report the formation of drug delivery systems from original thermoresponsive block copolymers containing lipid-based segments. Two acrylate monomers derived from palmitic- or oleic-acid−based diacylglycerols (DAGs) were synthesized and polymerized by the reversible addition−fragmentation chain transfer (RAFT) method. Well-defined DAG-based polymers with targeted molar masses and narrow molar mass distributions were next used as macro-chain transfer agents (macroCTAs) for the polymerization of N-isopropylacrylamide (NIPAAm) or N-vinylcaprolactam (NVCL). The obtained amphiphilic block copolymers were formed into polymeric nanoparticles (PNPs) with and without encapsulated doxorubicin and characterized. Their biological assessment indicated appropriate cytocompatibility with the representatives of normal cells. Furthermore, compared to the free drug, increased cytotoxicity and apoptosis or necrosis induction in breast cancer cells was documented, including a highly aggressive and invasive triple-negative MDA-MB-231 cell line.This work was financially supported by the National Science Centre, Poland, grant no. NCN/2019/35/B/ST5/03391 (A.Z.W.). Analyses were performed in the Centre of Synthesis and Analysis BioNanoTechno of the University of Bialystok. The equipment in the Centre was funded by the EU as a part of the Operational Program Development of Eastern Poland 2007−2013, projects: POPW.01.03.00-20-034/09-00 and POPW.01.03.00-20-004/11. The biological part was performed at the Medical University of Bialystok SUB/1/DN/22/002/3327 (K.N.L.).Karolina H. Markiewicz: [email protected] Z. Wilczewska: [email protected] Kurowska - Faculty of Chemistry, University of BialystokKarolina H. Markiewicz - Faculty of Chemistry, University of BialystokKatarzyna Niemirowicz-Laskowska - Department of Experimental Pharmacology, Medical University of BialystokMathias Destarac - Laboratoire IMRCP, CNRS UMR 5623, Paul Sabatier UniversityPrzemysław Wielgat - Department of Clinical Pharmacology, Medical University of BialystokIwona Misztalewska-Turkowicz - Faculty of Chemistry, University of BialystokPaweł Misiak - − Faculty of Chemistry, University of BialystokHalina Car - Department of Experimental Pharmacology, Medical University of BialystokAgnieszka Z. Wilczewska - Faculty of Chemistry, University of BialystokSung, Y. K.; Kim, S. W. Recent Advances in Polymeric Drug Delivery Systems. Biomater. Res. 2020, 24 (1), 12.Kumar, R.; Santa Chalarca, C. F.; Bockman, M. R.; Bruggen, C. V.; Grimme, C. J.; Dalal, R. J.; Hanson, M. G.; Hexum, J. K.; Reineke, T. M. Polymeric Delivery of Therapeutic Nucleic Acids. Chem. Rev. 2021, 121 (18), 11527−11652Bochicchio, S.; Lamberti, G.; Barba, A. 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Doxorubicin-loaded polymeric nanoparticles containing ketoester-based block and cholesterol moiety as specific vehicles to fight estrogen-dependent breast cancer

The presented research concerns the preparation of polymer nanoparticles (PNPs) for the delivery of doxorubicin. Several block and statistical copolymers, composed of ketoester derivative, N-isopropylacrylamide, and cholesterol, were synthesized. In the nanoprecipitation process, doxorubicin (DOX) molecules were kept in spatial polymeric systems. DOX-loaded PNPs show high efcacy against estrogen-dependent MCF-7 breast cancer cell lines despite low doses of DOX applied and good compatibility with normal cells. Research confrms the efect of PNPs on the degradation of the biological membrane, and the accumulation of reactive oxygen species (ROS), and the ability to cell cycle arrest are strictly linked to cell death.This work was fnancially supported by the National Science Centre, Poland, grant no. NCN/2016/21/B/ST5/01365.Katarzyna Niemirowicz‑Laskowska: [email protected] Z. Wilczewska: [email protected]ł Misiak - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Białystok, PolandKatarzyna Niemirowicz‑Laskowska - Department of Experimental Pharmacology, Medical University of Bialystok, Mickiewicza 2A, 15‑089 Białystok, PolandKarolina H. Markiewicz - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Białystok, PolandPrzemysław Wielgat - Department of Clinical Pharmacology, Medical University of Bialystok, Białystok, PolandIzabela Kurowska - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Białystok, PolandRobert Czarnomysy - Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15‑089 Białystok, PolandIwona Misztalewska‑Turkowicz - Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15‑245 Białystok, PolandHalina Car - Department of Experimental Pharmacology, Medical University of Bialystok, Mickiewicza 2A, 15‑089 Białystok, PolandKrzysztof Bielawski - Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15‑089 Białystok, PolandAgnieszka Z. 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Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus

Group B Streptococcus (GBS) causes invasive infections in human newborns. We recently showed that the GBS beta-protein attenuates innate immune responses by binding to sialic acid-binding immunoglobulin-like lectin 5 (Siglec-5), an inhibitory receptor on phagocytes. Interestingly, neutrophils and monocytes also express Siglec-14, which has a ligand-binding domain almost identical to Siglec-5 but signals via an activating motif, raising the possibility that these are paired Siglec receptors that balance immune responses to pathogens. Here we show that beta-protein-expressing GBS binds to both Siglec-5 and Siglec-14 on neutrophils and that the latter engagement counteracts pathogen-induced host immune suppression by activating p38 mitogen-activated protein kinase (MAPK) and AKT signaling pathways. Siglec-14 is absent from some humans because of a SIGLEC14-null polymorphism, and homozygous SIGLEC14-null neutrophils are more susceptible to GBS immune subversion. Finally, we report an unexpected human-specific expression of Siglec-5 and Siglec-14 on amniotic epithelium, the site of initial contact of invading GBS with the fetus. GBS amnion immune activation was likewise influenced by the SIGLEC14-null polymorphism. We provide initial evidence that the polymorphism could influence the risk of prematurity among human fetuses of mothers colonized with GBS. This first functionally proven example of a paired receptor system in the Siglec family has multiple implications for regulation of host immunity

Can creditors protect themselves? : categorization and protection of individual groups of creditors through bond covenants

The proposed company law legislative reforms concerning deregulation of the capital maintenance regime give rise to a question about the need for implementation of the alternative creditors protection instruments. However, in the current inter-reformation period it is worth to solve a fundamental issue, which is whether in the present normative and economic Polish environment the interference of commercial companies law in the area of creditor protection through normative tools remains legitimate, or perhaps creditors are able to take care of their interests based on contractual tools. The purpose of the article is to classify, characterize and assess the potential of individual groups of creditors to independently protect their bargain through the most common and most effective contractual instrument of creditors' protection - bond covenants. In order to achieve that, the article transplants the Anglo-Saxon doctrinal discussion into the Polish market realities