Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles
Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles
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DOI：
10.3109/17435390.2011.633714
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发表时间：
2013-02-01
期刊：
影响因子：
5
通讯作者：
Marcelis, Antonius T. M.
中科院分区：
文献类型：
--
作者：
Bhattacharjee, Sourav;Ershov, Dmitry;Marcelis, Antonius T. M.
合成了一系列来自具有不同表面电荷的三嵌段共聚物（聚合物纳米颗粒（PNP））的单分散（45 +/-5 nm）荧光纳米颗粒，并研究了其在NR 8383和Caco-2细胞中的细胞毒性。阳性PNPs比中性和阴性PNPs具有更强的细胞毒性，并诱导更高的细胞内活性氧产生。具有季铵基团的阳性PNP的细胞毒性随着空间体积的增加而降低。还通过共聚焦激光扫描显微镜在NR 8383细胞中测试了这些不同PNP的细胞内摄取和细胞相互作用，其显示阳性PNP的摄取高于阴性PNP。此外，发现阳性PNP与细胞膜的相互作用更多，而阴性PNP主要通过溶酶体内吞作用内化。正性PNP的摄取随着正电荷周围的空间体积的增加而降低。观察到网格蛋白对阳性PNP和小窝蛋白受体对阴性PNP的表面电荷特异性相互作用。这些研究结果证实，表面电荷是重要的细胞毒性，这些PNP，而他们另外指出相当大的额外影响周围的空间屏蔽PNP细胞毒性的正电荷。
A series of monodisperse (45 +/- 5 nm) fluorescent nanoparticles from tri-block copolymers (polymeric nanoparticles (PNPs)) bearing different surface charges were synthesised and investigated for cytotoxicity in NR8383 and Caco-2 cells. The positive PNPs were more cytotoxic and induced a higher intracellular reactive oxygen species production than the neutral and negative ones. The cytotoxicity of positive PNPs with quaternary ammonium groups decreased with increasing steric bulk. The intracellular uptake and cellular interactions of these different PNPs were also tested in NR8383 cells by confocal laser scanning microscopy, which revealed higher uptake for positive than for negative PNPs. Also positive PNPs were found to interact much more with cell membranes, whereas the negative PNPs were internalised mainly by lysosomal endocytosis. Uptake of positive PNPs decreased with increasing steric bulk around the positive charge. A surface charge-specific interaction of clathrin for positive PNPs and caveolin receptors for negative PNPs was observed. These findings confirm that surface charge is important for the cytotoxicity of these PNPs, while they additionally point to considerable additional effects of the steric shielding around positive charges on PNP cytotoxicity.