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. 2020 Jun;32(24):e2000416.
doi: 10.1002/adma.202000416. Epub 2020 May 6.

Single siRNA Nanocapsules for Effective siRNA Brain Delivery and Glioblastoma Treatment

Yan Zou  1   2 , Xinhong Sun  1 , Yibin Wang  1 , Chengnan Yan  1 , Yanjie Liu  1 , Jia Li  2 , Dongya Zhang  1 , Meng Zheng  1 , Roger S Chung  2 , Bingyang Shi  1   2
Affiliations

Single siRNA Nanocapsules for Effective siRNA Brain Delivery and Glioblastoma Treatment

Yan Zou et al. Adv Mater. 2020 Jun.

Erratum in

Abstract

Small interfering RNA (siRNA) has been considered as a highly promising therapeutic agent for human cancer treatment including glioblastoma (GBM), which is a fatal disease without effective therapy methods. However, siRNA-based GBM therapy is seriously hampered by a number of challenges in siRNA brain delivery including poor stability, short blood circulation, low blood-brain barrier (BBB) penetration, and tumor accumulation, as well as inefficient siRNA intracellular release. Herein, an Angiopep-2 (Ang) functionalized intracellular-environment-responsive siRNA nanocapsule (Ang-NCss (siRNA)) is successfully developed as a safe and efficient RNAi agent to boost siRNA-based GBM therapy. The experimental results demonstrate that the developed Ang-NCss (siRNA) displays long circulation in plasma, efficient BBB penetration capability, and GBM accumulation and retention, as well as responsive intracellular siRNA release due to the unique design of small size (25 nm) with polymeric shell for siRNA protection, Ang functionalization for BBB crossing and GBM targeting, and disulfide bond as a linker for intracellular-environment-responsive siRNA release. Such superior properties of Ang-NCss (siRNA) result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. The developed siRNA nanocapsules provide a new strategy for RNAi therapy of GBM and beyond.

Keywords: RNAi therapy; blood-brain barrier; glioblastoma; nanocapsules; targeted delivery.

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