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| Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy | |
| Alternative Title | Biomaterials |
| Li, Yan1,2; Liu, Ruiyuan1,3; Yang, Jun1; Ma, Guanghui1; Zhang, Zhenzhong3; Zhang, Xin1 | |
| 2014-12-01 | |
| Source Publication | BIOMATERIALS
 |
| ISSN | 0142-9612 |
| Volume | 35Issue:36Pages:9731-9745 |
| Abstract | 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.; 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. |
| Keyword | Dual Sensitive Camptothecin Prodrug Poly(Carboxybetaine) Temporally Controlled Release Combination Therapy |
| Subtype | Article |
| WOS Headings | Science & Technology ; Technology |
| DOI | 10.1016/j.biomaterials.2014.08.022 |
| URL | 查看原文 |
| Indexed By | SCI |
| Language | 英语 |
| WOS Keyword | DRUG-DELIVERY ; GENE DELIVERY ; CO-DELIVERY ; POLYMERIC MICELLES ; SYSTEMIC DELIVERY ; ENDOSOMAL ESCAPE ; CANCER-THERAPY ; DOXORUBICIN ; PH ; NANOPARTICLES |
| WOS Research Area | Engineering ; Materials Science |
| WOS Subject | Engineering, Biomedical ; Materials Science, Biomaterials |
| WOS ID | WOS:000342890200017 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/11677 |
| Collection | 研究所（批量导入） |
| Affiliation | 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 |
| 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. |
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| Dual sensitive and t（6340KB） | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | Application Full Text | |
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