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Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery
Jiang, Tianyue1; Zhang, Zhenhai2; Zhang, Yinlong1; Lv, Huixia1; Zhou, Jianping1; Li, Caocao1; Hou, Lulu1; Zhang, Qiang3
关键词Ph-response Cell-penetrating Peptides Hyaluronic Acid Liposomes Tumor-targeted Drug Delivery
刊名BIOMATERIALS
2012-12-01
DOI10.1016/j.biomaterials.2012.09.027
33期:36页:9246-9258
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]MULTIFUNCTIONAL POLYMERIC MICELLE ; INTRACELLULAR DELIVERY ; GENE DELIVERY ; TAT PEPTIDE ; IN-VITRO ; NANOPARTICLES ; RICH ; EFFICIENT ; ARGININE ; CANCER
英文摘要

Dual-functional liposomes with pH-responsive cell-penetrating peptide (CPP) and active targeting hyaluronic acid (HA) were fabricated for tumor-targeted drug delivery. A series of synthetic tumor pH-triggered CPPs rich in arginines and histidines were screened by comparing tumor cellular uptake efficiency at pH 6.4 with at pH 7.4, and R6H4 (RRRRRRHHHH) was obtained with the optimal pH-response. To construct R6H4-modified liposomes (R6H4-L), stearyl R6H4 was anchored into liposomes due to hydrophobic interaction. HA was utilized to shield positive charge of R6H4-L to assemble HA-coated R6H4-L (HA-R6H4-L) by electrostatic effect for protecting the liposomes from the attack of plasma proteins. The rapid degradation of HA by hyaluronidase (HAase) was demonstrated by the viscosity and zeta potential detection, allowing the R6H4 exposure of HA-R6H4-L at HAase-rich tumor microenvironment as the protection by HA switches off and cell-penetrating ability of R6H4 turns on. After HAase treatment, paclitaxel-loaded HA-R6H4-L (PTX/HA-R6H4-L) presented a remarkably stronger cytotoxicity toward the hepatic cancer (HepG2) cells at pH 6.4 relative to at pH 7.4, and additionally coumarin 6-loaded HA-R6H4-L (C6/HA-R6H4-L) showed efficient intracellular trafficking including endosomal/lysosomal escape and cytoplasmic liberation by confocal laser scanning microscopy (CLSM). In vivo imaging suggested the reduced accumulation of near infrared dye 15 (NIRD15)-loaded HA-R6H4-L (NIRD/HA-R6H4-L) at the tumor site, when mice were pre-treated with an excess of free HA, indicating the active tumor targeting of HA. Indeed, PTX/HA-R6H4-L had the strongest antitumor efficacy against murine hepatic carcinoma (Heps) tumor xenograft models in vivo. These findings demonstrate the feasibility of using tumor pH-sensitive CPPs and active targeting HA to extend the applications of liposomal nanocarriers to efficient anticancer drug delivery. (C) 2012 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000310947100010
项目编号30973649 ; 30901867 ; 20090096110002 ; CX10B-373Z
资助机构National Natural Science Foundation of China ; Research Fund for the Doctoral Program of Higher Education of China ; National Basic Research Program of China
引用统计
被引频次:169[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51982
专题北京大学药学院
北京大学药学院_药剂学系
作者单位1.China Pharmaceut Univ, Dept Pharmaceut, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
2.Jiangsu Prov Acad Tradit Chinese Med, Nanjing 210000, Jiangsu, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Jiang, Tianyue,Zhang, Zhenhai,Zhang, Yinlong,et al. Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery[J]. BIOMATERIALS,2012,33(36):9246-9258.
APA Jiang, Tianyue.,Zhang, Zhenhai.,Zhang, Yinlong.,Lv, Huixia.,Zhou, Jianping.,...&Zhang, Qiang.(2012).Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery.BIOMATERIALS,33(36),9246-9258.
MLA Jiang, Tianyue,et al."Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery".BIOMATERIALS 33.36(2012):9246-9258.
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