Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy

Yu Ren, Ruirui Wang, Lizhang Gao, Ke Li, Xuan Zhou, Hua Guo, Chaoyong Liu, Donglin Han, Jianguo Tian, Qing Ye, Ye Tony Hu, Duxin Sun, Xubo Yuan, Ning Zhang

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Previous literature and our study showed the delivery sequence of microRNA inhibitor and chemotherapeutic compounds achieve distinct therapeutic anticancer efficacy. Yet, it is challenging to use nanoparticle to achieve sequential drug delivery. In the current study, we designed sequential co-delivery system using a near-infrared-radiation (NIR) responsive hollow gold nanoparticle (HGNPs) to achieve sequential release of microRNA inhibitor (miR-21i)/doxirubicin(Dox) in order to achieve synergistic efficacy. PAMAM modified HGNPs was used to encapsulate miR-21i and Dox. Upon entering tumor cells, miRNA-21i was released first to sensitize the cancer cells, the subsequent burst release of Dox was achieved by NIR triggered collapse of HGNPs. This sequential delivery of miRNA-21i and Dox produced a synergistic apoptotic response, thereby enhancing anticancer efficacy by 8-fold and increasing anti-cancer stem cell activity by 50-fold. The sequential delivery of miR-21i and Dox using HGNPs under NIR after intravenous administration showed high tumor accumulation and significantly improved efficacy, which was 4-fold compared to free Dox group. These data suggested that the sequential co-delivery of miR-21i followed by burst release Dox using NIR-responsive HGNPs sensitized cancer cells to chemotherapeutic compound, which provided a novel concept for co-delivery miRNA inhibitors and chemotherapeutic compounds to enhance their efficacy.

Original languageEnglish (US)
Pages (from-to)74-86
Number of pages13
JournalJournal of Controlled Release
Volume228
DOIs
StatePublished - Apr 28 2016

Keywords

  • Co-delivery
  • Controlled sequential release
  • Doxorubicin
  • Gold nanoparticle
  • MicroRNA-21

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Ren, Y., Wang, R., Gao, L., Li, K., Zhou, X., Guo, H., Liu, C., Han, D., Tian, J., Ye, Q., Hu, Y. T., Sun, D., Yuan, X., & Zhang, N. (2016). Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy. Journal of Controlled Release, 228, 74-86. https://doi.org/10.1016/j.jconrel.2016.03.008