Cation-free siRNA micelles as effective drug delivery platform and potent RNAi nanomedicines for glioblastoma therapy

Tong Jiang, Yongnan Qiao, Weimin Ruan, Dongya Zhang, Qingshan Yang, Guoying Wang, Qunzhi Chen, Fengping Zhu, Jinlong Yin, Yan Zou, Rongjun Qian, Meng Zheng, Bingyang Shi

    Research output: Contribution to journalArticlepeer-review

    66 Citations (Scopus)


    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.
    Original languageEnglish
    Article number2104779
    Pages (from-to)1-10
    Number of pages10
    JournalAdvanced Materials
    Issue number45
    Early online date18 Sept 2021
    Publication statusPublished - 11 Nov 2021


    • cation-free
    • glioblastoma
    • micelle
    • siRNA
    • spherical nucleic acid


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