CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.
Biomaterials. 2011 Nov;32(32):8291-303. doi: 10.1016/j.biomaterials.2011.07.037. Epub 2011 Jul 31.
The fate of nanomaterials with different sizes and charges in mitotic cells is of great importance but seldom explored. Herein we investigate the intracellular fate of negatively charged carboxylated polystyrene (COOH-PS) and positively charged amino-modified polystyrene (NH(2)-PS) nanoparticles of three different diameters (50, 100 and 500 nm) on cancer HeLa cells and normal NIH 3T3 cells during the cell cycles. The results showed that all the fluorescent PS nanoparticles differing in size and/or charge did not interact with chromosome reorganization and cytoskeleton assembly during the mitotic process in live cells. They neither disturbed chromosome reorganization nor affected the cytoskeleton reassembly in both normal and cancer cells. However, NH(2)-PS at the size of 50 nm caused G1 phase delay and a decrease of cyclin (D, E) expression, respectively. Moreover, NH(2)-PS displayed higher cellular toxicity and NH(2)-PS of 50 nm disturbed the integrity of cell membranes. Both cationic and anionic PS nanoparticles had a more pronounced effect on normal NIH 3T3 cells than cancer HeLa cell. Our research provides insight into the dynamic fate, intracellular behavior, and the effects of nanoparticles on spindle and chromosomes during cell division, which will enable the optimization of design and selection of much safer nanoparticles for lower risk to human health and widely medical applications.
不同大小和电荷的纳米材料在有丝分裂细胞中的命运非常重要，但很少被探索。在此，我们研究了三种不同直径（50、100 和 500nm）的带负电荷的羧基化聚苯乙烯（COOH-PS）和带正电荷的氨基修饰聚苯乙烯（NH2-PS）纳米颗粒在癌细胞 HeLa 和正常 NIH 3T3 细胞周期内的细胞内命运。结果表明，所有大小和/或电荷不同的荧光 PS 纳米颗粒在活细胞有丝分裂过程中均不与染色体重组和细胞骨架组装相互作用。它们既不干扰染色体重组，也不影响正常和癌细胞中的细胞骨架重组。然而，50nm 的 NH2-PS 分别导致 G1 期延迟和细胞周期蛋白（D、E）表达减少。此外，NH2-PS 表现出更高的细胞毒性，50nm 的 NH2-PS 破坏了细胞膜的完整性。阳离子和阴离子 PS 纳米颗粒对正常 NIH 3T3 细胞的影响比癌细胞 HeLa 更为明显。我们的研究深入了解了纳米颗粒在细胞分裂过程中对纺锤体和染色体的动态命运、细胞内行为以及对其的影响，这将使设计和选择更安全的纳米颗粒的优化，降低对人类健康的风险，并广泛应用于医学领域。
