CAS OpenIR  > 研究所(批量导入)
Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy
Alternative TitleBiomaterials
Li, Yan1,2; Liu, Ruiyuan1,3; Yang, Jun1; Ma, Guanghui1; Zhang, Zhenzhong3; Zhang, Xin1
2014-12-01
Source PublicationBIOMATERIALS
ISSN0142-9612
Volume35Issue:36Pages:9731-9745
AbstractThe 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.; 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.
KeywordDual Sensitive Camptothecin Prodrug Poly(Carboxybetaine) Temporally Controlled Release Combination Therapy
SubtypeArticle
WOS HeadingsScience & Technology ; Technology
DOI10.1016/j.biomaterials.2014.08.022
URL查看原文
Indexed BySCI
Language英语
WOS KeywordDRUG-DELIVERY ; GENE DELIVERY ; CO-DELIVERY ; POLYMERIC MICELLES ; SYSTEMIC DELIVERY ; ENDOSOMAL ESCAPE ; CANCER-THERAPY ; DOXORUBICIN ; PH ; NANOPARTICLES
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, Biomaterials
WOS IDWOS:000342890200017
Citation statistics
Cited Times:65[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/11677
Collection研究所(批量导入)
Affiliation1.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
Recommended Citation
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.
Files in This Item:
File Name/Size DocType Version Access License
Dual sensitive and t(6340KB)期刊论文出版稿限制开放CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Li, Yan]'s Articles
[Liu, Ruiyuan]'s Articles
[Yang, Jun]'s Articles
Baidu academic
Similar articles in Baidu academic
[Li, Yan]'s Articles
[Liu, Ruiyuan]'s Articles
[Yang, Jun]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Li, Yan]'s Articles
[Liu, Ruiyuan]'s Articles
[Yang, Jun]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.