Positively charged cyclodextrins as effective molecular transporters of active phosphorylated forms of gemcitabine into cancer cells
| Autor: | Rodriguez-Ruiz, Violeta, Maksimenko, Andrey, Salzano, Giuseppina, Lampropoulou, Maria, Lazarou, Yannis G., Agostoni, Valentina, Couvreur, Patrick, Gref, Ruxandra, Yannakopoulou, Konstantina |
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| Přispěvatelé: | Chornobyl Center for Nuclear Safety, Radioactive Waste and Radioecology, Institut Galien Paris-Sud (IGPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC), Laboratoire de Chimie Physique Macromoléculaire (LCPM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Physical Chemistry, National Center for Scientific Research 'Demokritos' (NCSR), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Antimetabolites
Antineoplastic Cyclodextrins Science Cytarabine Biological Transport Breast Neoplasms Models Theoretical [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences Lymphoma T-Cell Deoxycytidine Gemcitabine Article Drug Resistance Neoplasm Tumor Cells Cultured Medicine Humans Female Phosphorylation [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics ComputingMilieux_MISCELLANEOUS |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2017, 7 (1), ⟨10.1038/s41598-017-08727-y⟩ Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-08727-y⟩ |
| Popis: | Positively charged cyclodextrins (PCCDs) are molecular carriers of particular interest for their ability to readily enter into cancer cells. Of main interest, guanidino- and aminoalkyl- PCCDs can be conveniently synthesized and form stable and strong inclusion complexes with various active molecules bearing phosphate groups. We have addressed here the challenge to deliver into cancer cells phosphorylated gemcitabine drugs well known for their instability and inability to permeate cell membranes. NMR data corroborated by semiempirical theoretical calculations have shown that aminoalkyl-CDs form sufficiently stable complexes with both mono- and tri-phosphate forms of gemcitabine by simple mixing of the compounds in aqueous solution at physiological pH. Confocal microscopy and radioactivity counting experiments revealed that the developed systems enabled phosphorylated gemcitabine to penetrate efficiently into aggressive human breast cancer cells (MCF7), eventually leading to a substantial reduction of IC50 values. Moreover, compared to free drugs, phosphorylated metabolites of gemcitabine encapsulated in PCCDs displayed improved in vitro activities also on the aggressive human cancer cells CCRF-CEM Ara-C/8 C, a nucleoside transport-deficient T leukemia cell line. The current study offers the proof-of-principle that phosphorylated nucleoside drugs could be efficiently transported by PCCDs into cancer cells. |
| Databáze: | OpenAIRE |
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