中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy

文献类型:期刊论文

作者Li, Yan1,2; Liu, Ruiyuan1,3; Yang, Jun1; Ma, Guanghui1; Zhang, Zhenzhong3; Zhang, Xin1
刊名BIOMATERIALS
出版日期2014-12-01
卷号35期号:36页码:9731-9745
关键词Dual sensitive Camptothecin prodrug Poly(carboxybetaine) Temporally controlled release Combination therapy
ISSN号0142-9612
其他题名Biomaterials
中文摘要The combination of chemotherapeutic drug camptothecin (CPT) and siPlk1 could prohibit cancer development with combined effects. To ensure the two drugs could be simultaneously delivered to tumor region with high loading content, and the modulator siPlk1 could be released in advance to down-regulate the Plk1 expression to improve the sensitivity of CPT to cancer cells, dual sensitive and temporally controlled CPT prodrug based cationic liposomes with siPlk1 codelivery system was constructed. The pH-sensitive zwitterionic polymer poly(carboxybetaine) (PCB) was conjugated with CPT through pH and esterase-sensitive ester bond to enhance the stability and loading content of CPT. CPT-based cationic liposomes consisted of CPT-PCB prodrug and cationic lipid DDAB were then constructed for siRNA codelivery for combination therapy. The dual sensitive CPT-PCB/siPlk1 lipoplexes simultaneously delivered the two drugs to tumor cells and enabled a temporally controlled release of two drugs, that the siRNA was quickly released after 4 h incubation due to the protonation of PCB in endosomes/lysosomes, and CPT was released in a sustained manner in response to pH and esterase and highly accumulated in nucleus after 12 h incubation. The CPT-PCB/siPlk1 lipoplexes induced significant cell apoptosis and cytotoxicity in vitro with a synergistic effect. Furthermore, the dual sensitive CPT-PCB lipoplexes enhanced the tumor accumulation of the two payloads and exhibited a synergistic tumor suppression effect in tumor-bearing mice in vivo, which proved to be a promising delivery system for codelivery of CPT and siPlk1 for cancer therapy. (C) 2014 Elsevier Ltd. All rights reserved.
英文摘要The combination of chemotherapeutic drug camptothecin (CPT) and siPlk1 could prohibit cancer development with combined effects. To ensure the two drugs could be simultaneously delivered to tumor region with high loading content, and the modulator siPlk1 could be released in advance to down-regulate the Plk1 expression to improve the sensitivity of CPT to cancer cells, dual sensitive and temporally controlled CPT prodrug based cationic liposomes with siPlk1 codelivery system was constructed. The pH-sensitive zwitterionic polymer poly(carboxybetaine) (PCB) was conjugated with CPT through pH and esterase-sensitive ester bond to enhance the stability and loading content of CPT. CPT-based cationic liposomes consisted of CPT-PCB prodrug and cationic lipid DDAB were then constructed for siRNA codelivery for combination therapy. The dual sensitive CPT-PCB/siPlk1 lipoplexes simultaneously delivered the two drugs to tumor cells and enabled a temporally controlled release of two drugs, that the siRNA was quickly released after 4 h incubation due to the protonation of PCB in endosomes/lysosomes, and CPT was released in a sustained manner in response to pH and esterase and highly accumulated in nucleus after 12 h incubation. The CPT-PCB/siPlk1 lipoplexes induced significant cell apoptosis and cytotoxicity in vitro with a synergistic effect. Furthermore, the dual sensitive CPT-PCB lipoplexes enhanced the tumor accumulation of the two payloads and exhibited a synergistic tumor suppression effect in tumor-bearing mice in vivo, which proved to be a promising delivery system for codelivery of CPT and siPlk1 for cancer therapy. (C) 2014 Elsevier Ltd. All rights reserved.
WOS标题词Science & Technology ; Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]DRUG-DELIVERY ; GENE DELIVERY ; CO-DELIVERY ; POLYMERIC MICELLES ; SYSTEMIC DELIVERY ; ENDOSOMAL ESCAPE ; CANCER-THERAPY ; DOXORUBICIN ; PH ; NANOPARTICLES
收录类别SCI
原文出处://WOS:000342890200017
语种英语
WOS记录号WOS:000342890200017
公开日期2014-12-01
源URL[http://ir.ipe.ac.cn/handle/122111/11677]  
专题过程工程研究所_研究所(批量导入)
作者单位1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China
推荐引用方式
GB/T 7714
Li, Yan,Liu, Ruiyuan,Yang, Jun,et al. Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy[J]. BIOMATERIALS,2014,35(36):9731-9745.
APA Li, Yan,Liu, Ruiyuan,Yang, Jun,Ma, Guanghui,Zhang, Zhenzhong,&Zhang, Xin.(2014).Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy.BIOMATERIALS,35(36),9731-9745.
MLA Li, Yan,et al."Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy".BIOMATERIALS 35.36(2014):9731-9745.

入库方式: OAI收割

来源:过程工程研究所

浏览0
下载0
收藏0
其他版本

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。