Securing the Payload, Finding the Cell, and Avoiding the Endosome Peptide-Targeted, Fusogenic Porous Silicon Nanoparticles for Delivery of siRNA

Securing the Payload, Finding the Cell, and Avoiding the Endosome : Peptide-Targeted, Fusogenic Porous Silicon Nanoparticles for Delivery of siRNA

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 35 vom: 15. Aug., Seite e1902952
1. Verfasser: Kim, Byungji (VerfasserIn)
Weitere Verfasser: Sun, Si, Varner, Judith A, Howell, Stephen B, Ruoslahti, Erkki, Sailor, Michael J
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article cancer treatment immunotherapy liposomes macrophages ovarian cancer Drug Carriers Peptides RNA, Small Interfering Silicon Z4152N8IUI
Beschreibung
Zusammenfassung:© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Despite the promise of ribonucleic acid interference therapeutics, the delivery of oligonucleotides selectively to diseased tissues in the body, and specifically to the cellular location in the tissues needed to provide optimal therapeutic outcome, remains a significant challenge. Here, key material properties and biological mechanisms for delivery of short interfering RNAs (siRNAs) to effectively silence target-specific cells in vivo are identified. Using porous silicon nanoparticles as the siRNA host, tumor-targeting peptides for selective tissue homing, and fusogenic lipid coatings to induce fusion with the plasma membrane, it is shown that the uptake mechanism can be engineered to be independent of common receptor-mediated endocytosis pathways. Two examples of the potential broad clinical applicability of this concept in a mouse xenograft model of ovarian cancer peritoneal carcinomatosis are provided: silencing the Rev3l subunit of polymerase Pol ζ to impair DNA repair in combination with cisplatin; and reprogramming tumor-associated macrophages into a proinflammatory state
Beschreibung:Date Completed 20.01.2020
Date Revised 19.07.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201902952