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学科主题: 药学
题名:
pH-responsive complexes using prefunctionalized polymers for synchronous delivery of doxorubicin and siRNA to cancer cells
作者: Dong, Da-Wen; Xiang, Bai; Gao, Wei; Yang, Zhen-Zhen; Li, Jing-Quan; Qi, Xian-Rong
关键词: Prefunctionalized polymer ; One-step self-assembly ; Co-delivery ; pH-responsive ; Tumor microenvironment-sensitive ; nanocarriers ; Target
刊名: BIOMATERIALS
发表日期: 2013-07-01
DOI: 10.1016/j.biomaterials.2013.03.018
卷: 34, 期:20, 页:4849-4859
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]: Engineering ; Materials Science
关键词[WOS]: GENE DELIVERY ; CO-DELIVERY ; THERAPEUTIC AGENTS ; IN-VITRO ; NANOPARTICLES ; POLYETHYLENIMINE ; RESISTANCE ; DRUG ; NANOCARRIERS ; MECHANISM
英文摘要:

A nanocarrier delivery system that can simultaneously deliver a chemotherapeutic drug and siRNA to the tumor is emerging as a promising treatment strategy for cancer treatment. In this study, a multifunctional PHD/PPF/siRNA complexes was developed by one-step assembly of prefunctionalized polymers: PEI-HZ-DOX (PHD) and PEI-PEG-Folate (PPF) with siRNA. The PHD, a conjugate of PEI (polyethylenimine) with doxorubicin (DOX) via a pH-responsive hydrazone linkage, enables pH-controlled drug release. The PPF, a tumor-targeting folate ligand conjugated to PEI using polyethyleneglycol (PEG) as a linker, enables immune evasion and cell-specific targeting. The prefunctionalized PHD and PPF as well as the self-assembly complexes reveals advantage on safety in further application for siRNA delivery. By exploiting distinct triple ratios of PHD, PPF and siRNA during nanocomplexes formulation, the folate surface density, DOX loading amount and siRNA complexation can be precisely and reproducibly changed. The studies showed that the complexes was capable of delivering siRNA and DOX to cancerous cells and release synchronously in cell by acid-triggered manner, i.e. hydrazone bond cleavage and endosome/lysosome escape using flow cytometry and confocal laser scanning microscopy analysis. The results highlight the potential for therapeutic gene silencing in vitro and in vivo using RT-PCR and non-invasive in vivo imaging systems. The PHD/PPF/siRNA complexes can increase DOX and siRNA accumulation in cancerous cells and decrease the nonspecific distribution in normal tissues by the combination of EPR effect of nanocarriers, pH-triggered drug release, folate-mediated targeted delivery, and synergistic action of DOX and siRNA. (C) 2013 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 30970785 ; 81273454 ; 7132113 ; 2009CB930303 ; 2013CB932501 ; 20100001110056 ; BMU20110263
项目资助者: NSFC ; Beijing NSF ; National Basic Research Program ; Doctoral Foundation of the Ministry of Education ; Innovation Team of Ministry of Education
WOS记录号: WOS:000318464200016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56643
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100871, Peoples R China

Recommended Citation:
Dong, Da-Wen,Xiang, Bai,Gao, Wei,et al. pH-responsive complexes using prefunctionalized polymers for synchronous delivery of doxorubicin and siRNA to cancer cells[J]. BIOMATERIALS,2013,34(20):4849-4859.
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