NDLI: Cationic Poly(amidoamine) Dendrimer Induces Lysosomal Apoptotic Pathway at Therapeutically Relevant Concentrations

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Cationic Poly(amidoamine) Dendrimer Induces Lysosomal Apoptotic Pathway at Therapeutically Relevant Concentrations

Content Provider	PubMed Central
Author	Thomas, Thommey P. Majoros, Istvan Kotlyar, Alina Mullen, Douglas Holl, Mark M. Banaszak Baker, James R.
Abstract	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.
Related Links	http://dx.doi.org/10.1021/bm900683r
Ending Page	3214
Page Count	8
Starting Page	3207
File Format	PDF
ISSN	15257797
e-ISSN	15264602
Journal	Biomacromolecules
Issue Number	12
Volume Number	10
Language	English
Publisher Date	2009-12-14
Access Restriction	Open
Subject Keyword	Materials Chemistry Bioengineering Polymers and Plastics Biomaterials Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Materials Chemistry Biomaterials Bioengineering Polymers and Plastics

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