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Nanomaterials 2018, 8(3), 131; https://doi.org/10.3390/nano8030131

Enhanced Delivery of Therapeutic siRNA into Glioblastoma Cells Using Dendrimer-Entrapped Gold Nanoparticles Conjugated with β-Cyclodextrin

1
Department of Radiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
2
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
3
Université Paris Descartes, PRES Sorbonne Paris Cité, CNRS UMR 860, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologique, 45, rue des Saints Peres, 75006 Paris, France
4
CQM—Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal
5
Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, BP 44099, 31077 Toulouse CEDEX 4, France
6
Université de Toulouse, UPS, INPT, 31077 Toulouse CEDEX 4, France
*
Authors to whom correspondence should be addressed.
Received: 8 January 2018 / Revised: 28 January 2018 / Accepted: 29 January 2018 / Published: 27 February 2018
(This article belongs to the Special Issue Nanocolloids for Nanomedicine and Drug Delivery)
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Abstract

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. View Full-Text
Keywords: PAMAM dendrimers; β-CD; gold nanoparticles; gene silencing; siRNA PAMAM dendrimers; β-CD; gold nanoparticles; gene silencing; siRNA
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Qiu, J.; Kong, L.; Cao, X.; Li, A.; Wei, P.; Wang, L.; Mignani, S.; Caminade, A.-M.; Majoral, J.-P.; Shi, X. Enhanced Delivery of Therapeutic siRNA into Glioblastoma Cells Using Dendrimer-Entrapped Gold Nanoparticles Conjugated with β-Cyclodextrin. Nanomaterials 2018, 8, 131.

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