ILVO, Institute for Agricultural and Fisheries Research, Ankerstraat 1, B-8400 Oostende, Belgium.
Toxicology. 2010 Mar 10;269(2-3):170-81. doi: 10.1016/j.tox.2009.11.002. Epub 2009 Nov 26.
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.
基因传递已成为治疗各种人类疾病（包括感染，遗传疾病和肿瘤）的重要策略。为了避免使用病毒载体的困难，越来越多的非病毒基因传递纳米颗粒被开发出来。在这些新方法中，聚乙烯亚胺（PEI）目前被认为是最有效的聚合物基方法之一，被认为是金标准。当用于医学应用时，纳米颗粒的毒性是一个主要关注点。在这项研究中，我们选择了两种纳米颗粒进行深入的毒理学和生态毒理学评估，一种是经过良好表征的 PEI，另一种是新型聚合物聚（2-（二甲氨基）乙基甲基丙烯酸酯）（PDMAEMA）。在本研究中，我们评估了这些阳离子纳米颗粒本身以及被 DNA 覆盖的聚集体的毒性。由于这些纳米颗粒也经常在各种工业中大量使用，并可能进入环境，我们还对生态毒理学效应评估进行了初步评估。在项目期间研究了以下与纳米颗粒相关的方面：开发和表征，生态毒性，一般毒性和特定毒性。为此，使用了一系列不同的测试。这些测试的结论是，毒性在不同的纳米颗粒之间以及不同的 DNA 覆盖比之间有所不同。一般来说，在测试的不同系统中，PEI 聚合物比 PDMAEMA 聚合物毒性更大。对于聚集体也是如此，并且电荷比越高，聚集体的毒性就越大。我们的研究还清楚地表明，需要进行广泛的毒性测试，以进行全面的风险评估。我们的研究对两种生物医学纳米颗粒进行了这样的综合分析。
