Eco-, geno- and human toxicology of bio-active nanoparticles for biomedical applications.
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.
Robbens
Johan
J
ILVO, Institute for Agricultural and Fisheries Research, Ankerstraat 1, B-8400 Oostende, Belgium. Johan.Robbens@ilvo.vlaanderen.be <Johan.Robbens@ilvo.vlaanderen.be>
Vanparys
Caroline
C
Nobels
Ingrid
I
Blust
Ronny
R
Van Hoecke
Karen
K
Janssen
Colin
C
De Schamphelaere
Karel
K
Roland
Kathleen
K
Blanchard
Gersande
G
Silvestre
Frédéric
F
Gillardin
Virginie
V
Kestemont
Patrick
P
Anthonissen
Roel
R
Toussaint
Olivier
O
Vankoningsloo
Sébastien
S
Saout
Christelle
C
Alfaro-Moreno
Ernesto
E
Hoet
Peter
P
Gonzalez
Laetitia
L
Dubruel
Peter
P
Troisfontaines
Paul
P
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
D016207:Cytokines; D004785:Environmental Pollutants; D011109:Polymethacrylic Acids; C511861:poly(2-(diisopropylamino)ethyl methacrylate); D011094:Polyethyleneimine