title: Eco-, geno- and human toxicology of bio-active nanoparticles for biomedical applications.
abstract: Gene delivery has become an increasingly important strategy for treating a variety of human diseases, including infections, genetic disorders and tumours. To avoid the difficulties of using viral carriers, more and more non-viral gene delivery nanoparticles are developed. Among these new approaches polyethylene imine (PEI) is currently considered as one of the most effective polymer based method solution and considered as the gold standard. The toxicity of nanoparticles is a major concern when used for medical application. In this study we chose two nanoparticles for an in depth toxicological and ecotoxicological evaluation, one well characterized, PEI, and another novel polymer, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA). In the present study we have assessed the toxicity of these cation nanoparticles as such and of the polyplexes - nanoparticles covered with DNA. As these nanoparticles are also frequently used in high volumes in various industries and as such may enter in the environment, we also made an initial assessment of ecotoxicological effects assessment. The following nanoparticles related aspects have been studied during the project: development and characterization, ecotoxicity, general toxicity and specific toxicity. To this end a battery of different tests was used. The conclusion of these tests is that toxicity is varying between different nanoparticles and between different DNA covering ratios. In general, in the different systems tested, the PEI polymer is more toxic than the PDMAEMA polymer. The same difference is seen for the polyplexes and the higher the charge ratio, the more toxic are the polyplexes. Our study also clearly shows the need for a broad spectrum of toxicity assays for a comprehensive risk assessment. Our study has performed such a comprehensive analysis of two biomedical nanoparticles.
authors: ILVO, Institute for Agricultural and Fisheries Research, Ankerstraat 1, B-8400 Oostende, Belgium. Johan.Robbens@ilvo.vlaanderen.be <Johan.Robbens@ilvo.vlaanderen.be>
authors: Johan
authors: J
authors: Robbens
authors: Caroline
authors: C
authors: Vanparys
authors: Ingrid
authors: I
authors: Nobels
authors: Ronny
authors: R
authors: Blust
authors: Karen
authors: K
authors: Van Hoecke
authors: Colin
authors: C
authors: Janssen
authors: Karel
authors: K
authors: De Schamphelaere
authors: Kathleen
authors: K
authors: Roland
authors: Gersande
authors: G
authors: Blanchard
authors: Frédéric
authors: F
authors: Silvestre
authors: Virginie
authors: V
authors: Gillardin
authors: Patrick
authors: P
authors: Kestemont
authors: Roel
authors: R
authors: Anthonissen
authors: Olivier
authors: O
authors: Toussaint
authors: Sébastien
authors: S
authors: Vankoningsloo
authors: Christelle
authors: C
authors: Saout
authors: Ernesto
authors: E
authors: Alfaro-Moreno
authors: Peter
authors: P
authors: Hoet
authors: Laetitia
authors: L
authors: Gonzalez
authors: Peter
authors: P
authors: Dubruel
authors: Paul
authors: P
authors: Troisfontaines
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000196:embryology; D000818:Animals; D024803:Biomedical Enhancement; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D056890:Eukaryota / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D011094:Polyethyleneimine / Q000737:chemistry / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000633:toxicity*; D012867:Skin / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods; D014981:Xenopus
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D011109:Polymethacrylic Acids; C511861:poly(2-(diisopropylamino)ethyl methacrylate); D011094:Polyethyleneimine