Peptide PHSCNK as an integrin α5β1 antagonist targets stealth liposomes to integrin-overexpressing melanoma

被引：27

作者：

Dai, Wenbing ^{[1
]}

Yang, Tingyuan ^{[1
]}

Wang, Yiguang ^{[1
]}

Wang, Xueqing ^{[1
]}

Wang, Jiancheng ^{[1
]}

Zhang, Xuan ^{[1
]}

Zhang, Qiang ^{[1
]}

机构：

[1] Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2012年 / 8卷 / 07期

关键词：

Targeted delivery system; Liposomes; Doxorubicin; PHSCNK; Integrins; STERICALLY STABILIZED LIPOSOMES; IMPROVED ANTITUMOR EFFICACY; LOADED LIPOSOMES; IN-VIVO; INTRACELLULAR DELIVERY; TUMOR NEOVASCULATURE; BREAST-CANCER; RGD PEPTIDE; DOXORUBICIN; CELLS;

D O I：

10.1016/j.nano.2012.01.003

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

As an integrin alpha(5)beta(1) antagonist, N-acetyl-proline-histidine-serine-cysteine-asparagine-amide (Ac-PHSCN-NH2) is currently in phase II trials for various cancer therapies. In this study Ac-PHSCNK-NH2 (PHSCNK) was used as a novel homing peptide to prepare ligand-targeted liposomes loaded with doxorubicin (PHSCNK-PL-DOX), with the hypothesis that the therapy target of integrin alpha(5)beta(1) may also serve as a delivery target. The stealth liposomes loaded with doxorubicin (PL-DOX) were used as the control. PHSCNK-PL-DOX demonstrated an enhanced intracellular uptake and a greater cytotoxicity against melanoma B16F10 cells in comparison with PL-DOX. The novel targeted formulation displayed stronger tumor inhibition and prolonged survival time in comparison with controls in C57BL/6mice bearing B16F10 tumors, and it exhibited less heart toxicity in hematoxylin-eosin (H&E) staining of tissues. Taking the pharmacokinetics and biodistribution results into account, the authors conclude that alpha(5)beta(1) integrin-mediated liposomes might be used as a potential delivery system for targeted tumor therapy. From the Clinical Editor: Lactosyl-norcantharidin TMC nanoparticles were found superior in comparison with Lac-NCTD and Lac-NCTD chitosan nanoparticles from the standpoint of antitumor activity on murine hepatocarcinoma 22 subcutaneous model. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：1152 / 1161

页数：10

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