Brain-targeted polymersome codelivery of siRNA and temozolomide for effective glioblastoma chemo-RNAi synergistic therapy

Meng Zheng, Chengnan Yan, Qingshan Yang, Feiyan Zhu, Qiuli Du, Xue Xia, Marco Morsch, Albert Lee, Jinglong Yin, Yan Zou, Bingyang Shi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
141 Downloads (Pure)

Abstract

Temozolomide (TMZ) is a clinically approved drug for glioblastoma (GBM) therapy. However, as a result of methylguanine-DNA-methyltransferase (MGMT), which is able to repair damaged DNA-damage repairing, TMZ usually yields unsatisfactory therapeutic effects. Small interfering RNA (siRNA) is a potential alteration tool for sensitivity of TMZ by targeting DNA repair enzymes. However, a suitable TMZ and siRNA codelivery system that can effectively and actively co-deliver siRNA/TMZ into the brain tumor is lacking. In this study, we constructed an angiopep-2 decorated polymersomal delivery system to co-deliver TMZ/siRNA for synergistic GBM therapy. This targeted polymersomal nanomedicine not only enhanced the circulation time of siRNA/TMZ in blood but also improved their blood-brain barrier (BBB) crossing and GBM targeting ability. Moreover, when we co-administered siRNAs specific to retinoblastoma binding protein 4 (RBBP4) together with TMZ in GBM cells, these RBBP4-specific siRNA (siRBBP4) modulated the sensitivity of TMZ by regulating MGMT, and thus showed a powerful synergistic anti-tumor effect. We demonstrated that angiopep-2 decorated polymersomal siRBBP4/TMZ co-loaded nanomedicines are capable of inhibiting tumor growth and significantly improved life expectancy of orthotropic GBM bearing mice. Overall, our study suggests that such a polymersomal TMZ/siRNA codelivery system provides a robust and potent nanoplatform for targeted GBM chemo-RNAi therapy.

Original languageEnglish
Pages (from-to)203-210
Number of pages8
JournalChemPhysMater
Volume1
Issue number3
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Polymersome
  • siRNA
  • TMZ
  • Glioblastoma
  • Brain targeting

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