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学科主题: 药学
题名:
Novel CD44 receptor targeting multifunctional "nano-eggs" based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells
作者: Chen, Daquan1,2; Wang, Guohua3; Song, Weiguo4; Zhang, Qiang1,2
关键词: Double pH-sensitive ; CD44 receptor targeting ; Nano-eggs ; Co-delivery ; Cancer cells and cancer stem cells ; Nanomedicine ; Health effects
刊名: JOURNAL OF NANOPARTICLE RESEARCH
发表日期: 2015-10-24
DOI: 10.1007/s11051-015-3217-9
卷: 17, 期:10
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
研究领域[WOS]: Chemistry ; Science & Technology - Other Topics ; Materials Science
关键词[WOS]: CALCIUM-PHOSPHATE NANOPARTICLES ; KETAL-BASED CHITOSAN ; POLYMERIC MICELLES ; PROSTATE-CANCER ; SELF-RENEWAL ; TUMOR-CELLS ; IN-VITRO ; DRUG ; HYALURONAN ; RESISTANCE
英文摘要:

Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the "nano-eggs.′′ The formed nano-eggs had a smaller size (120.6 +/- 4.5 nm) than oHM micelles (158.6 +/- 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the "nano-eggs′′ were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug delivery to both cancer cells and cancer stem cells.

语种: 英语
所属项目编号: 81302718 ; 81573614 ; 2015M570907
项目资助者: National Natural Science Foundation of China ; Postdoctoral Science Foundation of China
WOS记录号: WOS:000365433600001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50144
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Yantai Univ, Sch Pharm, Yantai 264005, Peoples R China
3.China Acad Chinese Med Sci, Inst Chinese Materia Madica, Beijing 100700, Peoples R China
4.Shouguang Fukang Pharmceutial Co Ltd, Shouguang 262700, Peoples R China

Recommended Citation:
Chen, Daquan,Wang, Guohua,Song, Weiguo,et al. Novel CD44 receptor targeting multifunctional "nano-eggs" based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells[J]. JOURNAL OF NANOPARTICLE RESEARCH,2015,17(10).
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