iRGD decorated lipid-polymer hybrid nanoparticles for targeted co-delivery of doxorubicin and sorafenib to enhance anti-hepatocellular carcinoma efficacy

被引：103

作者：

Zhang, Jinming ^{[1
]}

Hu, Jie ^{[1
,2
]}

Chan, Hon Fai ^{[3
]}

Skibba, Melissa ^{[2
]}

Liang, Guang ^{[2
]}

Chen, Meiwan ^{[1
]}

机构：

[1] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China

[2] Wenzhou Med Univ, Sch Pharmaceut Sci, Chem Biol Res Ctr, Wenzhou, Zhejiang, Peoples R China

[3] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2016年 / 12卷 / 05期

基金：

中国国家自然科学基金;

关键词：

Hepatocellular carcinoma; Active targeting; Doxorubicin; Sorafenib; iRGD peptide; RECEPTOR-MEDIATED ENDOCYTOSIS; DRUG-DELIVERY; TUMOR; APOPTOSIS; NANOCARRIERS; COMBINATION; INHIBITION; NECROSIS; PLATFORM;

D O I：

10.1016/j.nano.2016.01.017

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

The combination of doxorubicin (DOX) with sorafenib (SOR) has proven an effective strategy to enhance anti-hepatocellular carcinoma (HCC) efficacy. However, respective in vivo pharmacokinetic profiles and different endocytosis capacities of these two drugs greatly hinder their current application. Herein, the tumor-targeting peptide iRGD decorated lipid-polymer hybrid nanoparticles (NPs) with a shell-core structure were developed for co-delivery of DOX and SOR (DOX+SOR/iRGD NPs). After the drug ratio was optimized, the stabilized DOX + SOR/iRGD NPs were prepared. Through the iRGD-integrin recognition, DOX + SOR/iRGD NPs showed synergistic cytotoxicity, pro-apoptotic ability and enhanced internalization rate in human liver cancer HepG2 cells. In vivo pharmacokinetic result demonstrated that an extended circulation and bioavailability of DOX + SOR/iRGD NPs than free drugs. More importantly, DOX + SOR/iRGD NPs significantly enhanced antitumor efficiency in HCC xenograft mouse models. Overall, this study describes a promising nanoparticulate drug co-delivery strategy to combine clinical anticancer drugs and enhance anti-HCC efficacy. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：1303 / 1311

页数：9

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