Self-assembling doxorubicin-prodrug nanoparticles as siRNA drug delivery system for cancer treatment: in vitro and in vivo
Liu, Hongmei1,2; Qiao, Chenmeng3; Yang, Jun1; Weng, Jie3; Zhang, Xin1
刊名JOURNAL OF MATERIALS CHEMISTRY B
2014-09-21
卷号2期号:35页码:5910-5924
关键词TARGETED CO-DELIVERY POLO-LIKE KINASES POLYMERIC MICELLES ANTICANCER DRUGS THERAPY CELLS GENE CHEMOTHERAPY DAUNOMYCIN NANOCARRIERS
ISSN号2050-750X
其他题名J. Mat. Chem. B
中文摘要Co-delivery of siRNAs and chemotherapeutic drugs to kill tumors have achieved superior tumor growth inhibition. However, due to siRNAs and chemotherapeutic drugs with different molecular properties, co-delivery carriers use more cationic materials to bind siRNAs and excessive inert materials to embed drugs, causing low drug-loading contents and systemic toxicity. To achieve this goal, doxorubicin (DOX) is chemically conjugated to stearoyl chloride (C18) through N-methyldiethanol amine (N) as cross-linker to form amphiphilic C18-N-DOX. C18-N-DOX contains a tertiary amine that can complex siRNAs at low pH (pH 3) and reduce the density of the positive charges on the surface of NPs at physiological pH (pH 7.4). C18-N-DOX, together with 1,2-distearoyl-sn-g/ycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) DSPE-PEG2000, self-assemble into DOX-prodrug nanoparticles (DOX-prodrug NPs), which bind siRNAs in citrate buffer (pH 3) to form DOX-prodrug NPs/siRNA. After replacing citrate buffer (pH 3) with PBS (pH 7.4), DOX-prodrug NPs/siRNA have slight negative charges due to complexed more siRNAs. In this study, clear evidence is shown that DOX-prodrug NPs can deliver siRNA to the same tumor cells both in vitro and in vivo. Moreover, DOX-prodrug NPs/siRNA show a great effect on inhibiting tumor cell growth both in vitro and in vivo. Therefore, the DOX-prodrug NPs are promising candidates as siRNAs delivery system for tumor therapy.
英文摘要Co-delivery of siRNAs and chemotherapeutic drugs to kill tumors have achieved superior tumor growth inhibition. However, due to siRNAs and chemotherapeutic drugs with different molecular properties, co-delivery carriers use more cationic materials to bind siRNAs and excessive inert materials to embed drugs, causing low drug-loading contents and systemic toxicity. To achieve this goal, doxorubicin (DOX) is chemically conjugated to stearoyl chloride (C18) through N-methyldiethanol amine (N) as cross-linker to form amphiphilic C18-N-DOX. C18-N-DOX contains a tertiary amine that can complex siRNAs at low pH (pH 3) and reduce the density of the positive charges on the surface of NPs at physiological pH (pH 7.4). C18-N-DOX, together with 1,2-distearoyl-sn-g/ycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) DSPE-PEG2000, self-assemble into DOX-prodrug nanoparticles (DOX-prodrug NPs), which bind siRNAs in citrate buffer (pH 3) to form DOX-prodrug NPs/siRNA. After replacing citrate buffer (pH 3) with PBS (pH 7.4), DOX-prodrug NPs/siRNA have slight negative charges due to complexed more siRNAs. In this study, clear evidence is shown that DOX-prodrug NPs can deliver siRNA to the same tumor cells both in vitro and in vivo. Moreover, DOX-prodrug NPs/siRNA show a great effect on inhibiting tumor cell growth both in vitro and in vivo. Therefore, the DOX-prodrug NPs are promising candidates as siRNAs delivery system for tumor therapy.
WOS标题词Science & Technology ; Technology
类目[WOS]Materials Science, Biomaterials
研究领域[WOS]Materials Science
关键词[WOS]TARGETED CO-DELIVERY ; POLO-LIKE KINASES ; POLYMERIC MICELLES ; ANTICANCER DRUGS ; THERAPY ; CELLS ; GENE ; CHEMOTHERAPY ; DAUNOMYCIN ; NANOCARRIERS
收录类别SCI
原文出处://WOS:000341274300020
语种英语
WOS记录号WOS:000341274300020
公开日期2014-09-30
内容类型期刊论文
版本出版稿
源URL[http://ir.ipe.ac.cn/handle/122111/11468]  
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.Southwest Jiaotong Univ, Sch Mat Sci & Engn, Key Lab Adv Technol Mat, Chengdu 610031, Sichuan, Peoples R China
推荐引用方式
GB/T 7714
Liu, Hongmei,Qiao, Chenmeng,Yang, Jun,et al. Self-assembling doxorubicin-prodrug nanoparticles as siRNA drug delivery system for cancer treatment: in vitro and in vivo[J]. JOURNAL OF MATERIALS CHEMISTRY B,2014,2(35):5910-5924.
APA Liu, Hongmei,Qiao, Chenmeng,Yang, Jun,Weng, Jie,&Zhang, Xin.(2014).Self-assembling doxorubicin-prodrug nanoparticles as siRNA drug delivery system for cancer treatment: in vitro and in vivo.JOURNAL OF MATERIALS CHEMISTRY B,2(35),5910-5924.
MLA Liu, Hongmei,et al."Self-assembling doxorubicin-prodrug nanoparticles as siRNA drug delivery system for cancer treatment: in vitro and in vivo".JOURNAL OF MATERIALS CHEMISTRY B 2.35(2014):5910-5924.
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