Bioreducible zinc(II)–dipicolylamine functionalized hyaluronic acid mediates safe siRNA delivery and effective glioblastoma RNAi therapy

Meng Zheng, Zhipeng Yang, Shizhu Chen, Haigang Wu, Yang Liu, Amanda Wright, Jeng-Wei Lu, Xue Xia, Albert Lee, Jinchao Zhang, Huijun Yin, Yingze Wang, Weimin Ruan, Xing-Jie Liang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

RNA interference (RNAi) is an emerging therapeutic modality for tumors. However, lack of a safe and efficient small interfering RNA (siRNA) delivery system limits its clinical application. Here, we report a bioreducible and less-cationic siRNA delivery carrier by conjugating Zn(II)–dipicolylamine complexes (Zn–DPA) onto hyaluronic acid (HA) via a redox-sensitive disulfide (-SS-) linker. Such polymer conjugates can formulate stable siRNA nanomedicines via coordination between zinc ions of DPA and the anionic phosphate of siRNA. After the conjugates are taken up by cells, intracellular reduction stimulus subsequently triggers the release of siRNAs and elucidates the desired RNAi effect. Our studies showed the formulated siRNA nanomedicines can be efficiently delivered into tumor cells/tissues and mediates less cytotoxicities both in vitro and in vivo. More importantly, when applied in a xenograft glioblastoma tumor model, this siRNA nanomedicine demonstrated significantly enhanced antitumor ability comparing to naked siRNA. This work demonstrates that such bioreducible Zn–DPA-functionalized HA conjugates without using cationic material as a siRNA carrier represents a promising direction for RNAi-based cancer therapy.
Original languageEnglish
Pages (from-to)362-369
Number of pages8
JournalACS Applied Bio Materials
Volume2
Issue number1
DOIs
Publication statusPublished - 22 Jan 2019

Keywords

  • bioreducible
  • gene therapy
  • glioblastoma
  • siRNA delivery
  • zin(II)-dipicolylamine

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