title: Toxicity and proapoptotic activity of poly(propylene imine) glycodendrimers in vitro: considering their contrary potential as biocompatible entity and drug molecule in cancer.
abstract: Since the first dendrimers were synthesized, scientists around the world have studied their properties and potential applications. Cationic dendrimers are characterized by significant toxicity due to their interactions with cells components. The replacement of all cationic surface groups by neutral ones and therefore diminishing positive charge reduces the toxicity but may also lead to loss of dendrimers' desirable properties and restrict their biomedical applications. We have compared the cytotoxicity, as well as proapoptotic and antiproliferative activity of unmodified fourth generation PPI dendrimer (PPI-G4) and dendrimers modified with maltose (Mal) or maltotriose (Mal-III) - for full (dense shell - DS) or partial (open shell - OS) surface modifications. We have proved that among glycodendrimers, the OS-Mal PPI-G4 dendrimer is the most toxic, whereas DS-Mal-III molecule shows relatively weak or even no effect. We have also confirmed that OS dendrimers, both maltotriose and maltose modified, not only reduce cancer cells viability by inducing apoptosis but also inhibit their proliferation. The use of dendrimers as an active substance, which may be a drug per se is one of the most exciting and clinically important applications of cancer nanotechnology, therefore a partial modification of the surface appears to be a perfect solution for this purpose.
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland. Electronic address: barzie@biol.uni.lodz.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziemba
authors.affiliation: Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, ul. Pabianicka 62, 93-513 Lodz, Poland.
authors.forename: Ida
authors.initials: I
authors.lastname: Franiak-Pietryga
authors.affiliation: Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Pion
authors.affiliation: Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, D-01069 Dresden, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.affiliation: Laboratorio Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Maria Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.affiliation: Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, D-01069 Dresden, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Voit
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Klajnert-Maculewicz
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D006001:Glycoconjugates / Q000737:chemistry; D006801:Humans; D008320:Maltose / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011126:Polypropylenes / Q000737:chemistry*; D014312:Trisaccharides / Q000737:chemistry
chemical_list: D050091:Dendrimers; D006001:Glycoconjugates; D011126:Polypropylenes; D014312:Trisaccharides; C443641:poly(propyleneimine); C008317:maltotriose; D008320:Maltose
keywords: Apoptosis; Dendrimer; Glycodendrimer; PPI; Proliferation; Toxicity