Journal
BIOMACROMOLECULES
Volume 10, Issue 12, Pages 3207-3214Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bm900683r
Keywords
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Funding
- National Cancer Institute National Institutes of Health [1 R33 CA112141, 1 R21 RR02 1893]
- National Institute of Biomedical Imaging and Bio-Engineering, National Institutes of Health [RO1 EB005028]
- National Institute of Diabetes and Digestive and Kidney Diseases [NIH5P60 DK20572]
- NATIONAL CANCER INSTITUTE [R33CA112141] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [R21RR021893] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB005028] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P60DK020572] Funding Source: NIH RePORTER
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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 alkanization and induction of mitochondria-mediated apoptosis
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