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题名: A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells
作者: Shen, Zheyu1;  Wu, Hao2;  Yang, Sugeun3;  Ma, Xuehua1;  Li, Zihou1;  Tan, Mingqian2;  Wu, Aiguo1
关键词: Trojan-horse targeting strategy ;  MRI contrast agents ;  Active targetability to cancer cells ;  Non-specific uptake by non-cancerous cells
刊名: BIOMATERIALS
发表日期: 2015-11-01
DOI: 10.1016/j.biomaterials.2015.08.022
卷: 70, 页:1-11
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Technology
类目[WOS]: Engineering, Biomedical ;  Materials Science, Biomaterials
研究领域[WOS]: Engineering ;  Materials Science
英文摘要: One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells. Here, we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand. The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers. The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions. Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (Mm) contrast agents were encapsulated into albumin nanopartides (AN), and then folic acid (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and gel permeation chromatography (GPC) results confirm successful construction of PP-FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft density) and the molecular weight of PP (i.e. graft length) are optimized to be 132 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FR alpha at pH 7.4 and shrink to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the nonspecific uptake of the PP-FA-AN-FN by non-cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent. (C) 2015 Elsevier Ltd. All rights reserved.
关键词[WOS]: IRON-OXIDE NANOPARTICLES ;  MRI CONTRAST AGENT ;  DRUG-DELIVERY ;  CANCER-THERAPY ;  IN-VIVO ;  N-ISOPROPYLACRYLAMIDE ;  POLYMERIC MICELLE ;  ANTICANCER DRUG ;  LIVER-CANCER ;  PH
语种: 英语
WOS记录号: WOS:000362610600001
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/146591
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Ningbo Inst Mat Technol & Engn, Div Funct Mat & Nano Devices, Key Lab Magnet Mat & Devices, Ningbo 315201, Zhejiang, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian 116023, Peoples R China
3.Inha Univ, Sch Med, Dept New Drug Dev, Inchon 400712, South Korea

Recommended Citation:
Shen, Zheyu,Wu, Hao,Yang, Sugeun,et al. A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells[J]. BIOMATERIALS,2015,70:1-11.
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