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.
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.
We designed and synthetized several families of original amphiphilic fluorescent phosphorus dendron-based micelles showing relevant antiproliferative activities for use in the field of theranostic nanomedicine. Based on straightforward synthesis pathways, twelve amphiphilic phosphorus dendrons bearing 10 protonated cyclic amino groups (generation one), or 20 protonated amino groups (generation two), and one hydrophobic chain carrying one fluorophore moiety were created.. These original dendron-based micelles showed moderate to high antiproliferative activities against a panel of tumor cell lines. This paper presents for the first time the synthesis and our first investigations of original phosphorus dendron-based micelles for cancer therapy applications.
RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells. The synthesized Au PENPs were well characterized. The efficiency of siRNA delivery was appraised by flow cytometry, confocal microscopy imaging, and the protein expression level. Our results revealed that the Au PENPs were capable of delivering Bcl-2 siRNA to glioblastoma cells with an excellent transfection efficiency, leading to specific gene silencing in the target cells (22% and 25.5% Bcl-2 protein expression in vitro and in vivo, respectively) thanks to the RGD peptide-mediated targeting pathway. The designed RGD-targeted Au PENPs may hold great promise to be used as a novel vector for specific cancer gene therapy applications.
Combined incompatible and sterile insect technique (IIT-SIT) has been considered to be an effective and safe approach to control mosquito populations. Immobilization of male adults by chilling is a crucial process required for the packing, transportation and release of the mosquitoes during the implementation of IIT-SIT for mosquito control. In this study, effects of chilling on the Aedes albopictus males with triple Wolbachia infections (HC line), a powerful weapon to fight against the wild type Ae. albopictus population via IIT-SIT, were evaluated under both laboratory and field conditions. Irradiated HC (IHC) males were exposed to 1, 5 and 10˚C for 1, 2, 3, 6 and 24 h. The survival rate of the post-chilled IHC males was then monitored. Longevity of post-chilled IHC males was compared to non-chilled males under laboratory and semi-field conditions. Mating competitiveness of IHC/HC males after exposure to 5 or 10˚C for 0, 3 and 24 h was then evaluated. Effects of compaction and transportation under chilled conditions on the survival rate of IHC males were also monitored. The optimal chilling conditions for handling IHC males were temperatures between 5 and 10˚C for a duration of less than 3 h with no negative impacts on survival rate, longevity and mating competitiveness when compared to non-chilled males. However, the overall quality of postchilled IHC/HC males decreased when exposed to low temperatures for 24 h. Reduced survival was observed when IHC males were stored at 5˚C under a compaction height of 8 cm. Transportation with chilling temperatures fluctuating from 8 to 12˚C has no negative impact on the survival of IHC males. This study identified the optimal chilling temperature and duration for the handling and transportation of Ae. albopictus IHC male adults without any detrimental effect on their survival, longevity and mating competitiveness. Further studies are PLOS NEGLECTED TROPICAL DISEASES
Fluorescent derivatives of phosphorhydrazone dendrimers are reviewed. Diverse types of fluorophores have been used, such as pyrene, naphthol, anthracene, dansyl, diketone, phthalocyanine, maleimide, julolidine, rhodamine, fluorescein, or fluorene derivatives. The fluorescent groups can be located either as terminal groups on the surface, at the core, linked to the core (off‐center), or to the branches of the dendritic structure. After fundamental research on their synthesis, these compounds have been used in the fields of catalysis, nanomaterials, OLEDs, sensors and biology/nanomedicine, in particular for monitoring transfection, or for their anti‐inflammatory or anti‐cancer properties.
Dendrimer-entrapped gold nanoparticles modified with β-cyclodextrin can be synthesized and used as a non-viral vector for enhanced gene delivery applications.
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