Department of Neurochemistry, Institute of Structural Chemistry, Chemical Research Center, Hungarian Academy, Budapest, Hungary.
Nanotoxicology. 2012 Sep;6(6):576-86. doi: 10.3109/17435390.2011.591511. Epub 2011 Jun 20.
We report for the first time on neuronal signaling for the evaluation of interactions between native plasmamembrane and polyamidoamine (PAMAM) dendrimers. Generation 5 polycationic (G5-NH(2)), novel β-D-glucopyranose-conjugated G5-NH(2) and generation 4.5 polyanionic (G4.5-COONa) polyamidoamine (PAMAM) dendrimers (1-0.0001 mg/ml) were applied in acute brain slices. Functional toxicity assessments-validated by fluorescence imaging of dead cells-were performed by employing electrophysiological indicators of plasma membrane breakdown and synaptic transmission relapse. Irreversible membrane depolarization and decrease of membrane resistance predicted substantial functional neurotoxicity of unmodified G5-NH(2), but not of the G4.5-COONa PAMAM dendrimers. Model calculations suggested that freely moving protonated NH(2) groups of terminal monomeric units of PAMAM dendrimers may be able directly destroy the membrane or inhibit important K(+) channel function via contacting the positively charged NH(2). In accordance, conjugation of surface amino groups by β-D-glucopyranose units reduced functional neurotoxicity that may hold great potential for biomedical applications.
我们首次报道了用于评估天然质膜与聚酰胺胺（PAMAM）树枝状聚合物相互作用的神经元信号传导。第 5 代阳离子（G5-NH 2 ）、新型β-D-吡喃葡萄糖偶联的 G5-NH 2 和第 4.5 代阴离子（G4.5-COONa）聚酰胺胺（PAMAM）树枝状聚合物（1-0.0001mg/ml）被应用于急性脑切片。通过电生理指标测量质膜破裂和突触传递复发，采用荧光成像检测死细胞，进行功能毒性评估，以验证其有效性。不可逆的膜去极化和膜电阻的降低预测未修饰的 G5-NH 2 会产生实质性的功能神经毒性，但 G4.5-COONa PAMAM 树枝状聚合物则不会。模型计算表明，PAMAM 树枝状聚合物末端单体单元中自由移动的质子化 NH 2 基团可能直接通过与带正电荷的 NH 2 接触破坏膜或抑制重要的 K + 通道功能。相应地，通过β-D-吡喃葡萄糖单元对表面氨基的修饰降低了功能神经毒性，这可能在生物医学应用中具有巨大潜力。
