We report the use of arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for highly efficient and specific gene delivery to stem cells. In this study, generation 5 poly(amidoamine) dendrimers modified with RGD via a poly(ethylene glycol) (PEG) spacer and with PEG monomethyl ether were used as templates to entrap gold nanoparticles (AuNPs). The native and the RGD-modified PEGylated dendrimers and the respective well characterized Au DENPs were used as vectors to transfect human mesenchymal stem cells (hMSCs) with plasmid DNA (pDNA) carrying both the enhanced green fluorescent protein and the luciferase (pEGFPLuc) reporter genes, as well as pDNA encoding the human bone morphogenetic protein-2 (hBMP-2) gene. We show that all vectors are capable of transfecting the hMSCs with both pDNAs. Gene transfection using pEGFPLuc was demonstrated by quantitative Luc activity assay and qualitative evaluation by fluorescence microscopy. For the transfection with hBMP-2, the gene delivery efficiency was evaluated by monitoring the hBMP-2 concentration and the level of osteogenic differentiation of the hMSCs via alkaline phosphatase activity, osteocalcin 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. The coexistence of RGD and AuNPs rendered the designed dendrimeric vector with specific stem cell binding ability likely via binding of integrin receptor on the cell surface and improved three-dimensional conformation of dendrimers, which is beneficial for highly efficient and specific stem cell gene delivery applications.

Exploitation of novel hybrid nanomaterials for combinational tumor therapy is challenging. In this work, we synthesized dendrimer-modified MoS nanoflakes for combinational gene silencing and photothermal therapy (PTT) of cancer cells. Hydrothermally synthesized MoS nanoflakes were modified with generation 5 (G5) poly(amidoamine) dendrimers partially functionalized with lipoic acid via disulfide bond. The formed G5-MoS nanoflakes display good colloidal stability and superior photothermal conversion efficiency and photothermal stability. With the dendrimer surface amines on their surface, the G5-MoS nanoflakes are capable of delivering Bcl-2 (B-cell lymphoma-2) siRNA to cancer cells (4T1 cells, a mouse breast cancer cells) with excellent transfection efficiency, inducing 47.3% of Bcl-2 protein expression inhibition. In vitro cell viability assay data show that cells treated with the G5-MoS/Bcl-2 siRNA polyplexes under laser irradiation have a viability of 21.0%, which is much lower than other groups of single mode PTT treatment (45.8%) or single mode of gene therapy (68.7%). Moreover, the super efficacy of combinational therapy was further demonstrated by treating a xenografted 4T1 tumor model in vivo. These results suggest that the synthesized G5-MoS nanoflakes may be employed as a potential nanoplatform for combinational gene silencing and PTT of tumors.

Partially PEGylated dendrimer-entrapped gold nanoparticles can be used as a promising nanoplatform for highly efficient pDNA and siRNA delivery.

A facile supramolecular assembly approach has been developed to construct core–shell tecto dendrimers with aminated surfaces for enhanced gene delivery.

We describe a safe and highly effective non-viral vector system based on β-cyclodextrin (β-CD)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for improved delivery small interfering RNA (siRNA) to glioblastoma cells. In our approach, we utilized amine-terminated generation 5 poly(amidoamine) dendrimers partially grafted with β-CD as a nanoreactor to entrap Au NPs. The acquired β-CD-modified Au DENPs (Au DENPs-β-CD) were complexed with two different types of therapeutic siRNA (B-cell lymphoma/leukemia-2 (Bcl-2) siRNA and vascular endothelial growth factor (VEGF) siRNA). The siRNA compression ability of the Au DENPs-β-CD was evaluated by various methods. The cytocompatibility of the vector/siRNA polyplexes was assessed by viability assay of cells. The siRNA transfection capability of the formed Au DENPs-β-CD vector was evaluated by flow cytometric assay of the cellular uptake of the polyplexes and Western blot assays of the Bcl-2 and VEGF protein expression. Our data reveals that the formed Au DENPs-β-CD carrier enables efficiently delivery of siRNA to glioma cells, has good cytocompatibility once complexed with the siRNA, and enables enhanced gene silencing to inhibit the expression of Bcl-2 and VEGF proteins. The developed Au DENPs-β-CD vector may be used for efficient siRNA delivery to different biosystems for therapeutic purposes.