Cyclopamine treatment disrupts extracellular matrix and alleviates solid stress to improve nanomedicine delivery for pancreatic cancer

被引：20

作者：

Zhang, Bo ^{[1
]}

Wang, Honglan ^{[1
]}

Jiang, Ting ^{[1
]}

Jin, Kai ^{[2
]}

Luo, Zimiao ^{[2
]}

Shi, Wei ^{[1
]}

Mei, Heng ^{[1
]}

Wang, Huafang ^{[1
]}

Hu, Yu ^{[1
]}

Pang, Zhiqing ^{[2
]}

Jiang, Xinguo ^{[2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Inst Hematol, Wuhan 430022, Hubei, Peoples R China

[2] Fudan Univ, Minist Educ, Sch Pharm, Key Lab Smart Drug Delivery, 826 Zhangheng Rd, Shanghai 201203, Peoples R China

来源：

JOURNAL OF DRUG TARGETING | 2018年 / 26卷 / 10期

基金：

中国国家自然科学基金;

关键词：

cyclopamine; solid stress; pancreatic ductal adenocarcinoma; nanomedicine; fibronectins; DRUG-DELIVERY; TUMORS; CHEMOTHERAPY; STRATEGIES; THERAPY; NANOTHERAPEUTICS; NANOPARTICLES; THERAPEUTICS; BARRIERS; VESSELS;

D O I：

10.1080/1061186X.2018.1452243

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

As one of the most intractable tumours, pancreatic ductal adenocarcinoma (PDA) has a dense extracellular matrix (ECM) which could increase solid stress within tumours to compress tumour vessels, reduce tumour perfusion and compromise nanomedicine delivery for PDA. Thus, alleviating solid stress represents a potential therapeutic target for PDA treatment. In this study, cyclopamine, a special inhibitor of the hedgehog signalling pathway which contributes a lot to ECM formation of PDA, was exploited to alleviate solid stress and improve nanomedicine delivery to PDA. Results demonstrated that cyclopamine successfully disrupted ECM and lowered solid stress within PDA, which increased functional tumour vessels and resulted in enhanced tumour perfusion as well as improved tumour nanomedicine delivery in PDA-bearing animal models. Therefore, solid stress within PDA represents a new therapeutic target for PDA treatment.

引用

页码：913 / 919

页数：7

共 33 条

[31] Cyclopamine disrupts tumor extracellular matrix and improves the distribution and efficacy of nanotherapeutics in pancreatic cancer [J].