Hyaluronan-Based Nanocarriers with CD44-Overexpressed Cancer Cell Targeting

IMR OpenIR

	Hyaluronan-Based Nanocarriers with CD44-Overexpressed Cancer Cell Targeting
	S. S. Song; H. Qi; J. W. Xu; P. Guo; F. Chen; F. Li; X. G. Yang; N. C. Sheng; Y. L. Wu; W. S. Pan
	2014
发表期刊	Pharmaceutical Research
ISSN	0724-8741
卷号	31 期号:11 页码:2988-3005
摘要	The objective of the work was to evaluate the potential of hyaluronan-based nanoparticles as tumor-targeting nano-systems for CD44-overexpressed cancer therapy. The synthesized amphiphilic cholesteryl succinoyl hyaluronan (Chol-Suc-HA) conjugates self-assembled into docetaxel(DTX)-loaded nanoparticles in the aqueous environment. The physiochemical properties of Chol-Suc-HA-DTX NPs were characterized. The in vitro cytotoxicity of Chol-Suc-HA-DTX NPs against MCF-7, 4T1, A549 and L929 cells was evaluated using MTT and LDH assays. Moreover, the cellular uptake mechanism was investigated using the CLSM and flow cytometry. The in vivo animal experiments of Chol-Suc-HA-DTX NPs including pharmacokinetic evaluation, bio-distribution observed by EX vivo NIRF imaging and antitumor efficacy were also carried out in SD rats or 4T1 tumor-bearing BALB/c mice. The self-assembled Chol-Suc-HA-DTX NPs with different degree of substitution (DS) of hydrophobic moiety exhibited high drug loading, uniform particle size distribution and excellent in vitro stability. However, the plasma stability of Chol-Suc-HA-DTX NPs was significantly influenced by the DS of hydrophobic moiety. The higher the DS was, the more stable the NPs were. Cellular uptake demonstrated that Chol-Suc-HA-DTX NPs were internalized into cancer cells via CD44 receptor-mediated endocytosis. Compared with TaxotereA (R), Chol-Suc-HA-DTX NPs displayed remarkably higher cytotoxicity to CD44-positive cancer cells (MCF-7, 4T1, A549 cells). In vivo animal experiments confirmed that Chol-Suc-HA-DTX NPs with relatively high DS values exhibited prolonged circulation time, excellent tumor-targeting properties and efficient antitumor effects with extremely low systemic toxicity. In addition, blank Chol-Suc-HA NPs also slightly suppressed the tumor growth. Chol-Suc-HA NPs with a suitable DS value portend to be promising drug vehicles for systemic targeting of CD44-overexpressed cancers.
部门归属	[song, shuangshuang ; guo, pan ; chen, fen ; li, fei ; yang, xinggang ; pan, weisan] shenyang pharmaceut univ, sch pharm, shenyang 110016, peoples r china. [qi, huan ; xu, jingwen ; wu, yingliang] shenyang pharmaceut univ, coll life sci & biopharmaceut, shenyang 110016, peoples r china. [sheng, naicheng] univ chinese acad sci, inst met res, shenyang 110016, peoples r china. ; pan, ws (reprint author), shenyang pharmaceut univ, sch pharm, pob 122,103 wenhua rd, shenyang 110016, peoples r china. ; yingliang1016@163.com ; pwstfzy@163.com
关键词	Cd44-mediated Endocytosis Hyaluronan Interference With Endogenous Ha-cd44 Interaction Tumor-targeting Colon-carcinoma Cells Drug-delivery Brain Glioma Tumor-growth In-vivo Acid Nanoparticles Cd44 Therapy Doxorubicin
URL	查看原文
语种	英语
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/73371
专题	中国科学院金属研究所
推荐引用方式 GB/T 7714	S. S. Song,H. Qi,J. W. Xu,et al. Hyaluronan-Based Nanocarriers with CD44-Overexpressed Cancer Cell Targeting[J]. Pharmaceutical Research,2014,31(11):2988-3005.
APA	S. S. Song.,H. Qi.,J. W. Xu.,P. Guo.,F. Chen.,...&W. S. Pan.(2014).Hyaluronan-Based Nanocarriers with CD44-Overexpressed Cancer Cell Targeting.Pharmaceutical Research,31(11),2988-3005.
MLA	S. S. Song,et al."Hyaluronan-Based Nanocarriers with CD44-Overexpressed Cancer Cell Targeting".Pharmaceutical Research 31.11(2014):2988-3005.