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

卷:228

Article

Ren, Yu¹  Wang, Ruirui¹  Gao, Lizhang²  Li, Ke²  Zhou, Xuan³  Guo, Hua¹  Liu, Chaoyong²  Han, Donglin²  Tian, Jianguo⁴  Ye, Qing⁴  Hu, Ye Tony⁵  Sun, Duxin⁶  Yuan, Xubo²  Zhang, Ning¹ 

[1] Tianjin Med Univ, Tianjin Canc Inst & Hosp, Natl Clin Res Ctr Canc, Res Ctr Basic Med Sci, Tianjin 300070, Peoples R China

[2] Tianjin Univ, Sch Mat Sci & Engn, Tianjin 300072, Peoples R China

[3] Canc Inst & Hosp, Dept Head & Neck, Tianjin 300060, Peoples R China

[4] Nankai Univ, Sch Phys, Tianjin 300071, Peoples R China

[5] Houston Methodist Res Inst, Dept Nanomed, Houston, TX 77030 USA

[6] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, 428 Church St, Ann Arbor, MI 48109 USA

关键词: Co-delivery;    Controlled sequential release;    MicroRNA-21;    Doxorubicin;    Gold nanoparticle;   

DOI  :  10.1016/j.jconrel.2016.03.008

来源: Elsevier

【 摘 要 】

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 hollowgold 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. (C) 2016 Elsevier B.V. All rights reserved.

【 授权许可】

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