We report the use of RGD peptide-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for enhanced stem cell gene delivery applications. In this study, generation 5 poly(amidoamine) (PAMAM) dendrimers modified with Arg-Gly-Asp (RGD) peptide via a poly(ethelene glycol) (PEG) spacer and monomethyl ether PEG (G5.NH2-(PEG-RGD)10-mPEG10) were used as templates to entrap gold nanoparticles. The formed PEGylated dendrimers and Au DENPs with or without RGD were characterized via different techniques. These dendrimers and Au DENPs were then used as vector to transfect plasmid DNA (pDNA) carrying both luciferase (Luc) reporter gene and enhanced green fluorescent protein (EGFP) gene, and a pDNA reporting human bone morphogenetic protein-2 (hBMP-2) to human mesenchymal stem cells (hMSCs). We show that all vectors are able to transfect both pDNAs to hMSCs. For the former pDNA transfection, this can be demonstrated by quantitative Luc activity assay and qualitative fluorescence microscopy. For the transfection of the latter pDNA, the gene delivery efficiency can be evaluated by the level of osteogentic differentiation of hMSCs via alkaline phosphatase (ALP) activity, oseocalcin secretion, calcium deposition, and von Kossa staining assays. Our results reveal that the stem cell gene delivery efficiency is largely dependent on the composition and the surface functionality of the dendrimer-based vectors and follows the order of K4 > K2 > K3 > K1 > K0 (See  and caption). The coexistence of RGD and Au NPs renders the designed vector with specific stem cell binding ability via binding of avb3 integrin on the cell surface and improved 3-dimensional shape of dendrimers, which is beneficial for enhanced stem cell gene delivery applications.

RGD peptide-modified dendrimer-entrapped goldnanoparticles enable effective gene delivery to stem cells

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.