Reduced Cationic Nanoparticle Cytotoxicity Based on Serum Masking of Surface Potential.
Reduced Cationic Nanoparticle Cytotoxicity Based on Serum Masking of Surface Potential.
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DOI：
10.1166/jbn.2016.2134
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发表时间：
2016-01
影响因子：
2.9
通讯作者：
Serda RE
中科院分区：
文献类型：
--
作者：
McConnell KI;Shamsudeen S;Meraz IM;Mahadevan TS;Ziemys A;Rees P;Summers HD;Serda RE
具有阳离子部分（例如聚乙烯亚胺（PEI））的纳米颗粒的官能化增强了与细胞膜的结合;然而，它也破坏了细胞质膜和囊泡膜的完整性，导致细胞死亡。发现原代成纤维细胞对阳离子氧化铁纳米颗粒显示出高表面亲和力，并且比它们的永生化对应物具有更高的敏感性。在血清中存在递增的情况下用阳离子纳米颗粒处理细胞导致细胞死亡的相应线性减少。纳米颗粒的表面电位也随着血清的增加而线性降低，这与细胞死亡强烈负相关。虽然低剂量的纳米颗粒在25%血清中呈现无毒，但大剂量克服了毒性阈值。血清没有减少纳米颗粒与原代成纤维细胞的结合，表明纳米颗粒细胞毒性的降低是基于PEI表面的血清掩蔽，而不是暴露减少。原代内皮细胞同样对阳离子纳米颗粒的细胞毒性作用比其永生化的对应物更敏感，这适用于对阳离子微粒的细胞反应，尽管微粒的毒性比纳米颗粒低得多。
Functionalization of nanoparticles with cationic moieties, such as polyethyleneimine (PEI), enhances binding to the cell membrane; however, it also disrupts the integrity of the cell’s plasma and vesicular membranes, leading to cell death. Primary fibroblasts were found to display high surface affinity for cationic iron oxide nanoparticles and greater sensitivity than their immortalized counterparts. Treatment of cells with cationic nanoparticles in the presence of incremental increases in serum led to a corresponding linear decrease in cell death. The surface potential of the nanoparticles also decreased linearly as serum increased and this was strongly and inversely correlated with cell death. While low doses of nanoparticles were rendered non-toxic in 25% serum, large doses overcame the toxic threshold. Serum did not reduce nanoparticle association with primary fibroblasts, indicating that the decrease in nanoparticle cytotoxicity was based on serum masking of the PEI surface, rather than decreased exposure. Primary endothelial cells were likewise more sensitive to the cytotoxic effects of cationic nanoparticles than their immortalized counterparts, and this held true for cellular responses to cationic microparticles despite the much lower toxicity of microparticles compared to nanoparticles.