Hypoxia-responsive drug-drug conjugated nanoparticles for breast cancer synergistic therapy
文献类型：期刊论文
| 作者 | Zhang, Ruilong1,2; Li, Yan2; Zhang, Miao1,2; Tang, Qunwei1; Zhang, Xin2 |
| 刊名 | RSC ADVANCES
 |
| 出版日期 | 2016 |
| 卷号 | 6期号:36页码:30268-30276 |
| ISSN号 | 2046-2069 |
| 英文摘要 | 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. |
| WOS标题词 | Science & Technology ; Physical Sciences |
| 类目[WOS] | Chemistry, Multidisciplinary |
| 研究领域[WOS] | Chemistry |
| 关键词[WOS] | STEM-CELLS ; FLUORESCENT-PROBE ; TARGETING HYPOXIA ; TUMOR ; MICELLES ; DELIVERY ; NICHE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000373061600047 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/20979]  |
| 专题 | 过程工程研究所_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 |
| 推荐引用方式 GB/T 7714 | 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. |
入库方式： OAI收割
来源：过程工程研究所
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