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Hypoxia-responsive drug-drug conjugated nanoparticles for breast cancer synergistic therapy
Zhang, Ruilong1,2; Li, Yan2; Zhang, Miao1,2; Tang, Qunwei1; Zhang, Xin2
2016
发表期刊RSC ADVANCES
ISSN2046-2069
卷号6期号:36页码:30268-30276
摘要In order to eliminate tumors, it is necessary to kill differentiated cancer cells, cancer stem cells (CSCs) and the "vascular niche" synergistically. Although nanoparticles (NPs) have been used to deliver drugs to the action sites, inert materials with high toxicity may reduce the drug loading content and cause side-effects to kidneys and other organs in the course of degradation and excretion. Here, we report hypoxia-responsive drug-drug conjugated NPs to deliver three drugs to kill differentiated cancer cells, CSCs and the "vascular niche" synergistically, which could selectively release the drugs to treat cells in hypoxic tumors. For this purpose, an azobenzene (AZO) bond imparting hypoxia sensitivity and specificity as a crosslinker conjugated hydrophobic combretastatin A-4 (CA4) with hydrophilic irinotecan (IR) to form IR-AZO-CA4 amphiphilic molecules. These molecules self-assembled into NPs, which could encapsulate hydrophobic anti-CSCs drug cyclopamine (CP). The drug-drug conjugated NPs had high drug loading content. As expected, the AZO linker could be broken under hypoxia conditions and the NPs were disassembled to release drugs quickly. Confocal laser scanning microscopy (CLSM) results indicated that the IR-AZO-CA4/CP NPs could enhance the cellular uptake of drugs and the permeability of drugs to the inner of CSCs, beneficial for tumor therapy. Furthermore, the IR-AZO-CA4/CP NPs could inhibit the migration, invasion and mammosphere formation capacity of CSCs. More importantly, only IR-AZO-CA4/CP NPs could simultaneously inhibit differentiated cancer cells, CSCs and endothelial cells without interference on the cell under a normoxic environment. The present study suggests that the IR-AZO-CA4/CP NPs provide a promising therapeutic approach for anticancer treatment.
文章类型Article
WOS标题词Science & Technology ; Physical Sciences
DOI10.1039/c6ra01560c
收录类别SCI
语种英语
关键词[WOS]STEM-CELLS ; FLUORESCENT-PROBE ; TARGETING HYPOXIA ; TUMOR ; MICELLES ; DELIVERY ; NICHE
WOS研究方向Chemistry
WOS类目Chemistry, Multidisciplinary
项目资助者National Natural Science Foundation of China(315220023 ; National High Technology Research and Development Program(2014AA020708) ; Instrument Developing Project of the Chinese Academy of Sciences(YZ201313) ; "Strategic Priority Research Program" of the Chinese Academy of Sciences(XDA09030301-3) ; BeiJing National Science Foundation(Z141100000214010) ; 51373177)
WOS记录号WOS:000373061600047
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/20979
专题生化工程国家重点实验室
作者单位1.Ocean Univ China, Inst Mat Sci & Engn, Qingdao 266100, Shandong, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
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Zhang, Ruilong,Li, Yan,Zhang, Miao,et al. Hypoxia-responsive drug-drug conjugated nanoparticles for breast cancer synergistic therapy[J]. RSC ADVANCES,2016,6(36):30268-30276.
APA Zhang, Ruilong,Li, Yan,Zhang, Miao,Tang, Qunwei,&Zhang, Xin.(2016).Hypoxia-responsive drug-drug conjugated nanoparticles for breast cancer synergistic therapy.RSC ADVANCES,6(36),30268-30276.
MLA Zhang, Ruilong,et al."Hypoxia-responsive drug-drug conjugated nanoparticles for breast cancer synergistic therapy".RSC ADVANCES 6.36(2016):30268-30276.
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