Targeted and redox-responsive drug delivery systems based on carbonic anhydrase IX-decorated mesoporous silica nanoparticles for cancer therapy

被引：68

作者：

Chen, Minmin ^{[1
,2
]}

Hu, Jinxia ^{[1
,2
]}

Wang, Lujing ^{[1
]}

Li, Yanru ^{[3
]}

Zhu, Chenghao ^{[1
]}

Chen, Chen ^{[1
]}

Shi, Ming ^{[4
]}

Ju, Zhicheng ^{[1
]}

Cao, Xichuan ^{[1
]}

Zhang, Zhuoqi ^{[3
]}

机构：

[1] China Univ Min & Technol, Sch Phys & Mat, Xuzhou 221116, Jiangsu, Peoples R China

[2] China Univ Min & Technol, Sch Chem Engn & Technol, Xuzhou 221116, Jiangsu, Peoples R China

[3] Xuzhou Med Univ, Dept Cardiol, Affiliated Hosp, Xuzhou 221002, Jiangsu, Peoples R China

[4] Xuzhou Med Univ, Inst Canc, Xuzhou 221002, Jiangsu, Peoples R China

来源：

SCIENTIFIC REPORTS | 2020年 / 10卷 / 01期

基金：

中国国家自然科学基金;

关键词：

GOLD-NANOPARTICLES; NANOCARRIERS; NANOTUBES; VEHICLES; RELEASE; DESIGN;

D O I：

10.1038/s41598-020-71071-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In this work, we developed a new antibody-targeted and redox-responsive drug delivery system "MSNs-CAIX" by binding the anti-carbonic anhydrase IX antibody (A-CAIX Ab) on the surface of mesoporous silica nanoparticles (MSNs) via disulfide linkages. The design of the composite particles "MSNs-CAIX" involved the synthesis and surface functionalization with thiol groups, 2,2'-dipyridyl disulfide and CAIX antibody. In vitro, CAIX capping the doxorubicin hydrochloric (DOX)-loaded nanoparticles (DOX@MSNs-CAIX) exhibited effectively redox-responsive release in the presence of glutathione (GSH) owing to the cleavage of the disulfide bond. Compared with CAIX negative Mef cells (mouse embryo fibroblast), remarkably more DOX@MSNs-CAIX was internalized into CAIX positive 4T1 cells (mouse breast cancer cells) by receptor-mediation. Tumor targeting in vivo studies clearly demonstrated DOX@MSNs-CAIX accumulated in tumors and induced more tumor cells apoptosis in 4T1 tumor-bearing mice. With great potential, this drug delivery system is a promising candidate for targeted and redox-responsive cancer therapy.

引用

页数：12

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