Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, Michigan 48109, USA.
Biomacromolecules. 2009 Dec 14;10(12):3207-14. doi: 10.1021/bm900683r.
Poly(amidoamine) (PAMAM) dendrimers carrying different amounts of surface amino groups were synthesized and tested for their effects on cellular cytotoxicity, lysosomal pH, and mitochondria-dependent apoptosis. In KB cells, the PAMAM dendrimers were taken up into the lysosomal compartment, and they increased the lysosomal pH and cytotoxicity as a function of the number of surface amino groups on the dendrimer. PAMAM dendrimers that were surface-neutralized by acetylation of >80% of the surface amino groups failed to show any cytotoxicity. The positively charged, amine-terminated PAMAM dendrimer induced cellular apoptosis, as demonstrated by mitochondrial membrane potential changes and caspase activity measurements. These results suggest that PAMAM dendrimers are endocytosed into the KB cells through a lysosomal pathway, leading to lysosomal alkalinization and induction of mitochondria-mediated apoptosis.
聚（酰胺-胺）（PAMAM）树状大分子携带不同数量的表面氨基被合成并测试其对细胞毒性、溶酶体 pH 值和线粒体依赖性细胞凋亡的影响。在 KB 细胞中，PAMAM 树状大分子被摄取到溶酶体隔室中，并且它们增加溶酶体 pH 值和细胞毒性作为树状大分子表面氨基数量的函数。通过乙酰化 >80%的表面氨基而表面中和的 PAMAM 树状大分子未能显示任何细胞毒性。带正电荷、胺端基的 PAMAM 树状大分子诱导细胞凋亡，如线粒体膜电位变化和半胱天冬酶活性测量所示。这些结果表明，PAMAM 树状大分子通过溶酶体途径被内吞到 KB 细胞中，导致溶酶体碱化和诱导线粒体介导的细胞凋亡。
