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首页> 外文期刊>Biomaterials >Cytotoxicity and in vivo tissue compatibility of poly(amidoamine) with pendant aminobutyl group as a gene delivery vector.
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Cytotoxicity and in vivo tissue compatibility of poly(amidoamine) with pendant aminobutyl group as a gene delivery vector.

机译：聚氨基酰胺与氨基丁基侧基作为基因传递载体的细胞毒性和体内组织相容性。

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摘要

To design successful polymeric gene delivery vehicles with good biocompatibility and highly efficient gene transfer ability is one of the great scientific challenges in modern gene therapy. Poly(amidoamine) with pendant aminobutyl group (PAA-BA) has been proved to exhibit high transfection efficiency against bone marrow stromal cells (BMSCs) in vitro. In this work, based on previous research, PAA-BA's biocompatibility including in vitro cytotoxicity determined by effect on BMSCs' morphology, viability, membrane damage and apoptosisecrosis, and in vivo tissue compatibility determined by muscular and hepatic tissue response were further investigated in comparison to branched polyethylenimine (PEI) 25 kDa. The results demonstrated that PAA-BA possess much better cytocompatibility than PEI, yielding slight cell morphological change, high cell viability and mild effect on cell membrane damage as well as inducing less apoptoticecrotic cells at optimal N/P ratio. PAA-BA also exhibited better tissue compatibility, reflected by no or less inflammatory response in the site of muscle injection at the same (0.03% w/v) or higher concentration (0.1% w/v) and no hepatic tissue morphological change with normal hepatocytes. We concluded that PAA-BA was promising and safe candidate for in vitro BMSCs gene delivery and had potential for in future in vivo gene therapy.
机译：设计成功的具有良好生物相容性和高效基因转移能力的聚合基因传递载体是现代基因治疗中的重大科学挑战之一。已证明具有氨基丁基侧基的聚（酰胺基胺）（PAA-BA）在体外对骨髓基质细胞（BMSC）表现出高转染效率。在这项工作的基础上，基于先前的研究，进一步研究了PAA-BA的生物相容性，包括通过对BMSCs形态，活力，膜损伤和凋亡/坏死的影响确定的体外细胞毒性，以及通过肌肉和肝组织反应确定的体内组织相容性。与25 kDa的支链聚乙烯亚胺（PEI）的比较。结果表明，PAA-BA具有比PEI更好的细胞相容性，产生轻微的细胞形态变化，高细胞活力和对细胞膜损伤的温和作用，并在最佳N / P比下诱导较少的凋亡/坏死细胞。 PAA-BA还表现出更好的组织相容性，反映为在相同（0.03％w / v）或更高浓度（0.1％w / v）的肌肉注射部位无或少的炎症反应，正常肝组织形态无变化肝细胞。我们得出的结论是，PAA-BA是用于体外BMSCs基因递送的有希望且安全的候选者，并且在将来的体内基因治疗中具有潜力。

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