Cation-Free siRNA Micelles as Effective Drug Delivery Platform and Potent RNAi Nanomedicines for Glioblastoma Therapy

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - 33(2021), 45 vom: 06. Nov., Seite e2104779
1. Verfasser:	Jiang, Tong (VerfasserIn)
Weitere Verfasser:	Qiao, Yonghan, Ruan, Weimin, Zhang, Dongya, Yang, Qingshan, Wang, Guoying, Chen, Qunzhi, Zhu, Fengping, Yin, Jinlong, Zou, Yan, Qian, Rongjun, Zheng, Meng, Shi, Bingyang
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2021
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article cation-free glioblastoma micelle siRNA spherical nucleic acid Acrylic Resins Carbocyanines Cations Drug Carriers mehr... Micelles RNA, Small Interfering STAT3 Transcription Factor cyanine dye 5 poly-N-isopropylacrylamide 25189-55-3 Temozolomide YF1K15M17Y

Beschreibung
Zusammenfassung:	© 2021 Wiley-VCH GmbH. Nanoparticle-based small interfering RNA (siRNA) therapy shows great promise for glioblastoma (GBM). However, charge associated toxicity and limited blood-brain-barrier (BBB) penetration remain significant challenges for siRNA delivery for GBM therapy. Herein, novel cation-free siRNA micelles, prepared by the self-assembly of siRNA-disulfide-poly(N-isopropylacrylamide) (siRNA-SS-PNIPAM) diblock copolymers, are prepared. The siRNA micelles not only display enhanced blood circulation time, superior cell take-up, and effective at-site siRNA release, but also achieve potent BBB penetration. Moreover, due to being non-cationic, these siRNA micelles exert no charge-associated toxicity. Notably, these desirable properties of this novel RNA interfering (RNAi) nanomedicine result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. Moreover, as a novel type of polymeric micelle, the siRNA micelle displays effective drug loading ability. When utilizing temozolomide (TMZ) as a model loading drug, the siRNA micelle realizes effective synergistic therapy effect via targeting the key gene (signal transducers and activators of transcription 3, STAT3) in TMZ drug resistant pathways. The authors' results show that this siRNA micelle nanoparticle can serve as a robust and versatile drug codelivery platform, and RNAi nanomedicine and for effective GBM treatment
Beschreibung:	Date Completed 23.02.2022 Date Revised 23.02.2022 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-4095
DOI:	10.1002/adma.202104779