標題: Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer
作者: Li, Wei-Ming
Chiang, Chih-Sheng
Huang, Wei-Chen
Su, Chia-Wei
Chiang, Min-Yu
Chen, Jian-Yi
Chen, San-Yuan
材料科學與工程學系
Department of Materials Science and Engineering
關鍵字: Calcium phosphate;Combination chemotherapy;Magnetic targeting;Multi-drug resistance
公開日期: 28-十二月-2015
摘要: We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. (C) 2015 Elsevier B.V. All rights reserved.
URI: http://dx.doi.org/10.1016/j.jconrel.2015.10.020
http://hdl.handle.net/11536/129333
ISSN: 0168-3659
DOI: 10.1016/j.jconrel.2015.10.020
期刊: JOURNAL OF CONTROLLED RELEASE
Volume: 220
起始頁: 107
結束頁: 118
顯示於類別:期刊論文