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Biomacromolecules. 2009 Dec 14;10(12):3207-14. doi: 10.1021/bm900683r.

Cationic poly(amidoamine) dendrimer induces lysosomal apoptotic pathway at therapeutically relevant concentrations.

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  • 1Department 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. thommey@umich.edu


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.

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