title: 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.
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.
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Li
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chiang
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Su
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Chiang
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan.
authors.forename: Jian-Yi
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan. Electronic address: sanyuanchen@mail.nctu.edu.tw.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Chen
mesh_terms: D004999:Amifostine / Q000737:chemistry*; D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D003474:Curcumin / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D008280:Magnetics; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*
chemical_list: D004999:Amifostine; D002130:Calcium Phosphates; D003474:Curcumin; D003692:Delayed-Action Preparations; D004317:Doxorubicin; D005780:Gelatin; D018719:Erb-b2 Receptor Tyrosine Kinases; C020243:calcium phosphate; C508053:ERBB2 protein, human
keywords: Calcium phosphate; Combination chemotherapy; Magnetic targeting; Multi-drug resistance