Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy
Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy
复制标题
使用近红外响应空心金纳米颗粒顺序共同递送 miR-21 抑制剂，然后突然释放阿霉素，以增强抗癌功效
DOI：
10.1016/j.jconrel.2016.03.008
复制
发表时间：
2016-04-28
影响因子：
10.8
通讯作者：
Zhang, Ning
中科院分区：
文献类型：
--
作者：
Ren, Yu;Wang, Ruirui;Zhang, Ning
先前的文献和我们的研究表明，microRNA抑制剂和化疗化合物的递送顺序实现不同的治疗抗癌功效。然而，使用纳米颗粒来实现顺序药物递送是具有挑战性的。在本研究中，我们使用近红外辐射（NIR）响应性中空金纳米颗粒（HGNP）设计了顺序共递送系统，以实现microRNA抑制剂（miR-21 i）/多柔比星（Dox）的顺序释放，以实现协同功效。使用PAMAM修饰的HGNP包封miR-21 i和Dox。进入肿瘤细胞后，miRNA-21 i首先释放以致敏癌细胞，随后通过近红外触发HGNP的崩解实现Dox的爆发释放。miRNA-21 i和Dox的这种顺序递送产生了协同的凋亡反应，从而将抗癌功效提高了8倍，并将抗癌干细胞活性提高了50倍。静脉内给药后，在NIR下使用HGNP顺序递送miR-21 i和Dox显示出高肿瘤蓄积和显著提高的疗效，与游离Dox组相比，其提高了4倍。这些数据表明，使用NIR响应性HGNP顺序共递送miR-21 i，然后突释Dox使癌细胞对化疗化合物敏感，这为共递送miRNA抑制剂和化疗化合物以增强其功效提供了新的概念。(C)2016爱思唯尔B. V.保留所有权利。
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.