Targeted siRNA Delivery Using a Lipo‐Oligoaminoamide Nanocore with an Influenza Peptide and Transferrin Shell
Identifieur interne : 000D88 ( Main/Exploration ); précédent : 000D87; suivant : 000D89Targeted siRNA Delivery Using a Lipo‐Oligoaminoamide Nanocore with an Influenza Peptide and Transferrin Shell
Auteurs : Wei Zhang [Allemagne] ; Katharina Müller [Allemagne] ; Eva Kessel [Allemagne] ; Sören Reinhard [Allemagne] ; Dongsheng He [Allemagne] ; Philipp M. Klein [Allemagne] ; Miriam Höhn [Allemagne] ; Wolfgang Rödl [Allemagne] ; Susanne Kempter [Allemagne] ; Ernst Wagner [Allemagne]Source :
- Advanced Healthcare Materials [ 2192-2640 ] ; 2016-06.
Abstract
Developing RNA‐interference‐based therapeutic approaches with efficient and targeted cytosolic delivery of small interfering RNA (siRNA) is remaining a critical challenge since two decades. Herein, a multifunctional transferrin receptor (TfR)‐targeted siRNA delivery system (Tf&INF7) is designed based on siRNA complexes formed with the cationic lipo‐oligoamino amide 454, sequentially surface‐modified with polyethylene glycol‐linked transferrin (Tf) for receptor targeting and the endosomolytic peptide INF7 for efficient cytosolic release of the siRNA. Effective Tf&INF7 polyplex internalization and target gene silencing are demonstrated for the TfR overexpressing tumor cell lines (K562, D145, and N2a). Treatment with antitumoral EG5 siRNA results in a block of tumor cell growth and triggered apoptosis. Tf‐modified polyplexes are far more effective than the corresponding albumin‐ (Alb) or nonmodified 454 polyplexes. Competition experiments with excess of Tf demonstrate TfR target specificity. As alternative to the ligand Tf, an anti‐murine TfR antibody is incorporated into the polyplexes for specific targeting and gene silencing in the murine N2a cell line. In vivo distribution studies not only demonstrate an enhanced tumor residence of siRNA in N2a tumor‐bearing mice with the Tf&INF7 as compared to the 454 polyplex group but also a reduced siRNA nanoparticle stability limiting the in vivo performance.
A multifunctional transferrin‐receptor‐(TfR)‐targeted small interfering RNA (siRNA) delivery system is developed based on cationic siRNA complexes formed with precise sequence‐defined T‐shaped lipo‐oligomer, sequentially decorated with PEG‐linked transferrin‐(Tf)‐targeting ligand for surface shielding and specific cellular uptake through TfR, and with INF7 as small pH‐triggered peptide for endosomal escape.
Url:
DOI: 10.1002/adhm.201600057
Affiliations:
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Herein, a multifunctional transferrin receptor (TfR)‐targeted siRNA delivery system (Tf&INF7) is designed based on siRNA complexes formed with the cationic lipo‐oligoamino amide 454, sequentially surface‐modified with polyethylene glycol‐linked transferrin (Tf) for receptor targeting and the endosomolytic peptide INF7 for efficient cytosolic release of the siRNA. Effective Tf&INF7 polyplex internalization and target gene silencing are demonstrated for the TfR overexpressing tumor cell lines (K562, D145, and N2a). Treatment with antitumoral EG5 siRNA results in a block of tumor cell growth and triggered apoptosis. Tf‐modified polyplexes are far more effective than the corresponding albumin‐ (Alb) or nonmodified 454 polyplexes. Competition experiments with excess of Tf demonstrate TfR target specificity. As alternative to the ligand Tf, an anti‐murine TfR antibody is incorporated into the polyplexes for specific targeting and gene silencing in the murine N2a cell line. In vivo distribution studies not only demonstrate an enhanced tumor residence of siRNA in N2a tumor‐bearing mice with the Tf&INF7 as compared to the 454 polyplex group but also a reduced siRNA nanoparticle stability limiting the in vivo performance.</div><div type="abstract" xml:lang="en">A multifunctional transferrin‐receptor‐(TfR)‐targeted small interfering RNA (siRNA) delivery system is developed based on cationic siRNA complexes formed with precise sequence‐defined T‐shaped lipo‐oligomer, sequentially decorated with PEG‐linked transferrin‐(Tf)‐targeting ligand for surface shielding and specific cellular uptake through TfR, and with INF7 as small pH‐triggered peptide for endosomal escape.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Bavière</li><li>District de Haute-Bavière</li></region><settlement><li>Munich</li></settlement><orgName><li>Université Louis-et-Maximilien de Munich</li></orgName></list><tree><country name="Allemagne"><region name="Bavière"><name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name></region><name sortKey="He, Dongsheng" sort="He, Dongsheng" uniqKey="He D" first="Dongsheng" last="He">Dongsheng He</name><name sortKey="He, Dongsheng" sort="He, Dongsheng" uniqKey="He D" first="Dongsheng" last="He">Dongsheng He</name><name sortKey="Hohn, Miriam" sort="Hohn, Miriam" uniqKey="Hohn M" first="Miriam" last="Höhn">Miriam Höhn</name><name sortKey="Kempter, Susanne" sort="Kempter, Susanne" uniqKey="Kempter S" first="Susanne" last="Kempter">Susanne Kempter</name><name sortKey="Kessel, Eva" sort="Kessel, Eva" uniqKey="Kessel E" first="Eva" last="Kessel">Eva Kessel</name><name sortKey="Kessel, Eva" sort="Kessel, Eva" uniqKey="Kessel E" first="Eva" last="Kessel">Eva Kessel</name><name sortKey="Klein, Philipp M" sort="Klein, Philipp M" uniqKey="Klein P" first="Philipp M." last="Klein">Philipp M. Klein</name><name sortKey="Muller, Katharina" sort="Muller, Katharina" uniqKey="Muller K" first="Katharina" last="Müller">Katharina Müller</name><name sortKey="Reinhard, Soren" sort="Reinhard, Soren" uniqKey="Reinhard S" first="Sören" last="Reinhard">Sören Reinhard</name><name sortKey="Rodl, Wolfgang" sort="Rodl, Wolfgang" uniqKey="Rodl W" first="Wolfgang" last="Rödl">Wolfgang Rödl</name><name sortKey="Wagner, Ernst" sort="Wagner, Ernst" uniqKey="Wagner E" first="Ernst" last="Wagner">Ernst Wagner</name><name sortKey="Wagner, Ernst" sort="Wagner, Ernst" uniqKey="Wagner E" first="Ernst" last="Wagner">Ernst Wagner</name><name sortKey="Wagner, Ernst" sort="Wagner, Ernst" uniqKey="Wagner E" first="Ernst" last="Wagner">Ernst Wagner</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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