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Author: Janaszewska, Anna × DDC: 540 × Publisher: Basel : Molecular Diversity Preservation International × WGL Institute: IPF ×

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    In search of a phosphorus dendrimer-based carrier of rose bengal: Tyramine linker limits fluorescent and phototoxic properties of a photosensitizer
    (Basel : Molecular Diversity Preservation International, 2020) Sztandera, Krzysztof; Marcinkowska, Monika; Gorzkiewicz, Michał; Janaszewska, Anna; Laurent, Regis; Zabłocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara
    Photodynamic therapy (PDT) is a skin cancer treatment alternative to chemotherapy and radiotherapy. This method exploits three elements: a phototoxic compound (photosensitizer), light source and oxygen. Upon irradiation by light of a specific wavelength, the photosensitizer generates reactive oxygen species triggering the cascade of reactions leading to cell death. The positive therapeutic effect of PDT may be limited due to low solubility, low tumor specificity and inefficient cellular uptake of photosensitizers. A promising approach to overcome these obstacles involves the use of nanocarrier systems. The aim of this initial study was to determine the potential of the application of phosphorus dendrimers as carriers of a photosensitizer—rose bengal (RB). The primary goal involved the synthesis and in vitro studies of covalent drug–dendrimer conjugates. Our approach allowed us to obtain RB–dendrimer conjugates with the use of tyramine as an aromatic linker between the carrier and the drug. The compounds were characterized by FT-IR,1H NMR,13C NMR,31P NMR, size and zeta potential measurements and spectrofluorimetric analysis. The dialysis to check the drug release from the conjugate, flow cytometry to specify intracellular uptake, and singlet oxygen generation assay were also applied. Finally, we used MTT assay to determine the biological activity of the tested compounds. The results of our experiments indicate that the conjugation of RB to phosphorus dendrimers via the tyramine linker decreases photodynamic activity of RB. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Effcient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery
    (Basel : Molecular Diversity Preservation International, 2020) Gorzkiewicz, Michał; Kopeć, Olga; Janaszewska, Anna; Konopka, Małgorzata; Pędziwiatr-Werbicka, Elżbieta; Tarasenko, Irina I.; Bezrodnyi, Valeriy V.; Neelov, Igor M.; Klajnert-Maculewicz, Barbara
    The disruption of the cellular pathways of protein biosynthesis through the mechanism of RNA interference has been recognized as a tool of great diagnostic and therapeutic significance. However, in order to fully exploit the potential of this phenomenon, efficient and safe carriers capable of overcoming extra-and intracellular barriers and delivering siRNA to the target cells are needed. Recently, attention has focused on the possibility of the application of multifunctional nanoparticles, dendrimers, as potential delivery devices for siRNA. The aim of the present work was to evaluate the formation of dendriplexes using novel poly(lysine) dendrimers (containing lysine and arginine or histidine residues in their structure), and to verify the hypothesis that the use of these polymers may allow an efficient method of siRNA transfer into the cells in vitro to be obtained. The fluorescence polarization studies, as well as zeta potential and hydrodynamic diameter measurements were used to characterize the dendrimer:siRNA complexes. The cytotoxicity of dendrimers and dendriplexes was evaluated with the resazurin-based assay. Using the flow cytometry technique, the efficiency of siRNA transport to the myeloid cells was determined. This approach allowed us to determine the properties and optimal molar ratios of dendrimer:siRNA complexes, as well as to demonstrate that poly(lysine) dendrimers may serve as efficient carriers of genetic material, being much more effective than the commercially available transfection agent Lipofectamine 2000. This outcome provides the basis for further research on the application of poly(lysine) dendrimers as carriers for nucleic acids in the field of gene therapy. © 2020 by the authors.