Transferrin-inspired vehicles based on pH-responsive coordination bond to combat multidrug-resistant breast cancer

被引：64

作者：

He, Yu-Jing ^{[1
]}

Xing, Lei ^{[1
]}

Cui, Peng-Fei ^{[1
]}

Zhang, Jia-Liang ^{[1
]}

Zhu, Yong ^{[1
]}

Qiao, Jian-Bin ^{[1
]}

Lyu, Jin-Yuan ^{[1
]}

Zhang, Mei ^{[1
]}

Luo, Cheng-Qiong ^{[1
]}

Zhou, Yu-Xin ^{[1
]}

Lu, Na ^{[1
]}

Jiang, Hu-Lin ^{[1
,2
,3
]}

机构：

[1] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing 210009, Jiangsu, Peoples R China

[3] China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOMATERIALS | 2017年 / 113卷

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

Multidrug resistance; pH-responsive; Coordination bond; Transferrin-inspired nanoparticles; Doxorubicin; ANTICANCER DRUG-DELIVERY; MESOPOROUS SILICA NANOPARTICLES; ALBUMIN NANOPARTICLES; GENE DELIVERY; THERAPY; SYSTEMS; RELEASE; CARRIER; DESIGN; TRANSPORTERS;

D O I：

10.1016/j.biomaterials.2016.11.001

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

A novel biomimetic drug delivery system (BDDS) inspired by the pH-dependent ferric ion-transport and release manner of transferrin (Tf) was developed for combating multidrug-resistant breast cancer. Tf-inspired carrier was synthesized by modifying bovine serum albumin (BSA) with histamine (HA) through amide reaction to provide superior specific coordination sites for ferric ion-drug complexes, and self-assembled into nanoparticles (NPs) induced by coordination bond. Tf-inspired NPs were prepared via environment-friendly method, and well redispersed in saline after lyophilization. When internalized into tumor cells by SPARC (secreted protein acidic and rich in cysteine) mediated endocytosis, Tf-inspired NPs bypassed and decreased the P-glycoprotein-mediated drug efflux and led to more effective treatment of multidrug-resistant breast cancer compared with free drugs both in vitro and in vivo due to the enhanced cellular uptake and rapid pH-responsive drug release. Moreover, Tf-inspired NPs exhibited good biocompatibility and low systemic toxicity. Thus, our results demonstrate that Tf-inspired NPs based on coordination bond represent as a smart drug delivery strategy to combat multidrug-resistant cancer and have great potential for clinical applications in cancer therapy. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：266 / 278

页数：13

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