title: Internalization of Ineffective Platinum Complex in Nanocapsules Renders It Cytotoxic.
abstract: Anticancer therapy by platinum complexes, based on nanocarrier-based delivery, may offer a new approach to improve the efficacy and tolerability of the platinum family of anticancer drugs. The original rules for the design of new anticancer platinum drugs were affected by the fact that, although cisplatin (cis-[PtCl2 (NH3)2) was an anticancer drug, its isomer transplatin was not cytotoxic. For the first time, it is demonstrated that simple encapsulation of an inactive platinum compound in phospholipid bilayers transforms it into an efficient cytotoxic agent. Notably, the encapsulation of transplatin makes it possible to overcome the resistance mechanisms operating in cancer cells treated with cisplatin and prevents inactivation of transplatin in the extracellular environment. It is also shown that transplatin delivered to the cells in nanocapsules, in contrast to free (nonencapsulated) complex, forms cytotoxic cross-links on DNA.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 612 65, Brno, Czech Republic.
authors.forename: Oldrich
authors.initials: O
authors.lastname: Vrana
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 612 65, Brno, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Novohradsky
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17. listopadu 12, 77146, Olomouc, Czech Republic.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Medrikova
authors.affiliation: Materials Research Centre, Faculty of Chemistry, Brno University of Technology, Purkynova 118, 61200, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Burdikova
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 612 65, Brno, Czech Republic.|Department of Biophysics, Faculty of Science, Palacky University, 17. listopadu 12, 77146, Olomouc, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Stuchlikova
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 612 65, Brno, Czech Republic.|Department of Biophysics, Faculty of Science, Palacky University, 17. listopadu 12, 77146, Olomouc, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Kasparkova
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Kralovopolska 135, 612 65, Brno, Czech Republic. brabec@ibp.cz.
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D017671:Platinum Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D008081:Liposomes; D053769:Nanocapsules; D010743:Phospholipids; D017671:Platinum Compounds; D010984:Platinum; D004247:DNA; D002945:Cisplatin
keywords: DNA; cancer; liposomes; phospholipids; platinum