title: Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy.
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.
authors.affiliation: Tianjin Cancer Institute and Hospital, National Clinical Research Center of Cancer, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Tianjin Cancer Institute and Hospital, National Clinical Research Center of Cancer, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Wang
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Lizhang
authors.initials: L
authors.lastname: Gao
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Head & Neck, Tianjin, Cancer Institute and Hospital, Tianjin 300060, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Tianjin Cancer Institute and Hospital, National Clinical Research Center of Cancer, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Chaoyong
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Han
authors.affiliation: School of Physics, Nankai University, Tianjin 300071, PR China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Tian
authors.affiliation: School of Physics, Nankai University, Tianjin 300071, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston 77030, USA.
authors.forename: Ye Tony
authors.initials: YT
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China. Electronic address: xbyuan@tju.edu.cn.
authors.forename: Xubo
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Tianjin Cancer Institute and Hospital, National Clinical Research Center of Cancer, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China. Electronic address: zhangning@tmu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007259:Infrared Rays; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D050091:Dendrimers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C104700:PAMAM Starburst; D006046:Gold; D004317:Doxorubicin
keywords: Co-delivery; Controlled sequential release; Doxorubicin; Gold nanoparticle; MicroRNA-21