Synthetic PAMAM-RGD conjugates target and bind to odontoblast-like MDPC 23 cells and the predentin in tooth organ cultures.
Screening techniques now allow for the identification of small peptides that bind specifically to molecules like cells. However, despite the enthusiasm for this approach, single peptides often lack the binding affinity to target in vivo and regulate cell function. We took peptides containing the Arg-Gly Asp(RGD) motif that bind to the alpha Vbeta 3 integrin and have shown potential as therapeutics. To improve their binding affinity, we synthesized polyamidoamine (PAMAM) dendrimer-RGD conjugates that that contain 12-13 copies of the peptide. When cultured with human dermal microvessel endothelial cells (HDMEC), human vascular endothelial cells (HUVEC), or odontoblast-like MDPC-23 cells, the PAMAM dendrimer conjugate targets this receptor in a manner that is both time- and dose-dependent. Finally, this conjugate selectively targets RGD binding sites in the predentin of human tooth organ cultures. Taken together, these studies provide proof of principle that synthetic PAMAM-RGD conjugates could prove useful as carriers for the tissue-specific delivery of integrin-targeted therapeutics or imaging agents and could be used to engineer tissue regeneration.
Hill
Elliott
E
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA. eehill@umich.edu
Shukla
Rameshwer
R
Park
Steve S
SS
Baker
James R
JR
D000818:Animals; D002478:Cells, Cultured; D050091:Dendrimers; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009804:Odontoblasts / Q000187:drug effects*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014070:Tooth / Q000187:drug effects*
D050091:Dendrimers; D009842:Oligopeptides; C104700:PAMAM Starburst; D011073:Polyamines; C047981:arginyl-glycyl-aspartic acid