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

Wei Ming Li, Chih Sheng Chiang, Wei Chen Huang, Wei-Chia Su, Min Yu Chiang, Jian Yi Chen, San Yuan Chen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)107-118
Number of pages12
JournalJournal of Controlled Release
Volume220
DOIs
Publication statusPublished - Dec 28 2015
Externally publishedYes

Fingerprint

Amifostine
Gelatin
Nanoparticles
Breast Neoplasms
Curcumin
Doxorubicin
Ligands
Therapeutics
Multiple Drug Resistance
Drug Delivery Systems
Surface-Active Agents
calcium phosphate
Drug Liberation
Neoplasms
Apoptosis

Keywords

  • Calcium phosphate
  • Combination chemotherapy
  • Magnetic targeting
  • Multi-drug resistance

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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. / Li, Wei Ming; Chiang, Chih Sheng; Huang, Wei Chen; Su, Wei-Chia; Chiang, Min Yu; Chen, Jian Yi; Chen, San Yuan.

In: Journal of Controlled Release, Vol. 220, 28.12.2015, p. 107-118.

Research output: Contribution to journalArticle

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