Smart GSH/pH dual-bioresponsive degradable nanosponges based on beta-CD-appended hyper-cross-linked polymer for triggered intracellular anticancer drug delivery

作者全名："Dai, Yutong; Li, Qingman; Zhang, Shurong; Shi, Shan; Li, Yang; Zhao, Xudong; Zhou, Liping; Wang, Xin; Zhu, Yijian; Li, Wei"

作者地址："[Dai, Yutong; Zhang, Shurong; Shi, Shan; Li, Yang; Zhao, Xudong; Zhou, Liping; Wang, Xin; Zhu, Yijian; Li, Wei] Chongqing Med Univ, Sch Pharm, Dept Med Chem, Chongqing 400016, Peoples R China; [Li, Qingman] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Li, W (corresponding author), Chongqing Med Univ, Sch Pharm, Dept Med Chem, Chongqing 400016, Peoples R China."

来源：JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000679103000002

JCR分区：Q1

影响因子：5

年份：2021

卷号：64

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Nanosponges; Dual-bioresponsive; beta-Cyclodextrin; Controlled release; Hyper-cross-linked polymer

摘要："Efficient accumulation and on-demand intracellular drug release in the desired site are a crucial issue in developing ideal drug delivery systems (DDSs). Glutathione (GSH)/pH dual-bioresponsive degradable Nanosponges were developed based on beta-CD-appended hyper-cross-linked polymer by one-pot polymerization of acryloyl-6-ethylenediamine-6-deoxy-beta-Cyclodextrin (beta-CD-NH-ACy), acrylic acid (AA) and N,N-bis(acryloyl)-cystamine (BACy) as cross-linker to deliver doxorubcin (DOX) and investigated for GSH/pH triggered DOX release, in which the massive carboxyl and amino groups, and disulfide bonds were used as pH and GSH bioresponsive fragments, respectively. In the proposed DDSs, DOX was readily incorporated into the three dimensional networks of the Nanosponges either as inclusion complexes or as non-inclusion complexes, with a high drug loading capacity of 22.6%. In vitro release studies suggested that the Nanosponges exhibited GSH/pH triggered disintegration and drug release performance, in which DOX release was significantly accelerated in acidic (pH5.0) and cytosolic reduction (10 mM GSH) conditions, with similar to 77.0% of DOX release. The morphology changes of DOX@Nanosponges in releasing media (pH5.0, 10 mM GSH) were further studied by TEM. Confocal microscopy observation demonstrated that DOX was delivered and released into cytoplasm and nucleus of A549 cells in 7 h incubation with DOX@Nanosponges. MTT assays manifested that the Nanosponges exhibited low cytotoxicity up to a concentration of 1000 mu g/mL and DOX@Nanosponges had high anti-tumor activity. These findings demonstrated that the dual-bioresponsive Nanosponges may function as a promising platform for targeted delivery and intracellular drug controlled release in tumor therapy."

基金机构："Chongqing Municipality Education Commission [KJ1400212]; Municipal Science and Technology Committee of Chongqing [CSTC2014jcyjA0019]; School of Pharmacy, Chongqing Medical University"

基金资助正文："The authors acknowledge the financial support from Chongqing Municipality Education Commission (KJ1400212) , the Municipal Science and Technology Committee of Chongqing (CSTC2014jcyjA0019) , and School of Pharmacy, Chongqing Medical University."