Polymer conjugates of acridine-type anticancer drugs with pH-controlled activation

0377473 - ÚMCH 2013 RIV GB eng J - Journal Article
Sedláček, Ondřej - Hrubý, Martin - Studenovský, Martin - Větvička, D. - Svoboda, Jan - Kaňková, Dana - Kovář, J. - Ulbrich, Karel
Polymer conjugates of acridine-type anticancer drugs with pH-controlled activation.
Bioorganic & Medicinal Chemistry. Roč. 20, č. 13 (2012), s. 4056-4063. ISSN 0968-0896. E-ISSN 1464-3391
R&D Projects: GA ČR GPP207/10/P054; GA AV ČR IAAX00500803
Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510
Institutional support: RVO:61389013 ; RVO:61388971
Keywords : drug delivery systems * cancer therapy * controlled release
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 2.903, year: 2012

Acridines are potent DNA-intercalating anticancer agents with high in vivo anticancer effectiveness, but also severe side effects. We synthesized five 9-anilinoacridine-type drugs and their conjugates with biocompatible water-soluble hydrazide polymer carrier. All of the synthesized acridine drugs retained their in vitro antiproliferative properties. Their polymer conjugates were sufficiently stable at pH 7.4 (model of pH in blood plasma) while releasing free drugs at pH 5.0 (model of pH in endosomes). After internalization of the conjugates, the free drugs were released and are visible in cell nuclei by fluorescence microscopy. Their intercalation ability was proven using a competitive ethidium bromide displacement assay.
Permanent Link: http://hdl.handle.net/11104/0209620