Biomimetic nanoparticles delivered hedgehog pathway inhibitor to modify tumour microenvironment and improved chemotherapy for pancreatic carcinoma

被引：27

作者：

Jiang, Ting ^{[1
,2
]}

Zhang, Bo ^{[2
]}

Zhang, Long ^{[1
]}

Wu, Xuemei ^{[1
]}

Li, Haichun ^{[1
]}

Shen, Shun ^{[1
]}

Luo, Zimiao ^{[1
]}

Liu, Xianping ^{[1
]}

Hu, Yu ^{[2
]}

Pang, Zhiqing ^{[1
]}

Jiang, Xinguo ^{[1
]}

机构：

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

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

来源：

ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY | 2018年 / 46卷

基金：

中国国家自然科学基金;

关键词：

Biomimetic nanoparticles; tumour microenvironment; cyclopamine; chemotherapy; pancreatic ductal adenocarcinomas; RBC MEMBRANES; NANOTECHNOLOGY; EFFICACY; THERAPY;

D O I：

10.1080/21691401.2018.1445093

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The unique tumour microenvironment (TM) of pancreatic ductal adenocarcinoma (PDA) including highly desmoplastic ECM and low tumour perfusion supports a considerable barrier for effective delivery of nanomedicines. Effectively modulating PDA microenvironment to enhance tumour drug delivery represents a pinpoint in the field of PDA treatment. In this study, it was the first time that biomimetic nanoparticles, which were designed in the form of erythrocyte membrane-camouflaged PLGA nanoparticles (MNP), were utilized for PDA microenvironment modulation. Cyclopamine (CYC), an inhibitor of Hedgehog pathway that contributed a lot to desmoplastic ECM of PDA, was selected as the model drug and successfully encapsulated into MNP. Advantages of CYC-loaded MNP (CMNP) included favourable biocompatibility, long circulation time, and powerful TM modulation effect. CMNP could effectively deliver CYC to the tumour site, disrupt tumour ECM, increase functional vessels, and improve tumour perfusion significantly. The combination treatment with CMNP and PTX-loaded MNP (PMNP) successfully improved PTX delivery to tumour, resulting in remarkable tumour growth inhibition in vivo. Therefore, biomimetic nanoparticles provide a new strategy for modulating PDA TM and will have great potential to improve the therapeutic effects of nanomedicines for PDA patients.

引用

页码：S1088 / S1101

页数：14