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Epidermal Growth Factor–Ferritin H‐Chain Protein Nanoparticles for Tumor Active Targeting
Author(s) -
Li Xu,
Qiu Lihui,
Zhu Pei,
Tao Xinyi,
Imanaka Tadayuki,
Zhao Jing,
Huang Youguo,
Tu Yaping,
Cao Xuni
Publication year - 2012
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201200066
Subject(s) - epidermal growth factor , epidermal growth factor receptor , ferritin , chemistry , cancer research , breast cancer , nanoparticle , heparin binding egf like growth factor , internalization , cancer , microbiology and biotechnology , nanotechnology , receptor , biology , materials science , biochemistry , genetics
Human ferritin H‐chain protein (FTH1)‐based nanoparticles possess a precisely assembled nanometer‐scale structure and high safety. However, their applications for imaging and drug delivery towards cancer cells remain limited due to a lack of target specificity. Epidermal growth factor receptor (EGFR) is overexpressed in many malignant tissues including breast cancer, and has been used as a therapeutic target for cancer treatment. Herein, a genetic method is shown to generate EGF‐FTH1 chimeric proteins. EGF‐FTH1 nanoparticles with EGF on the surface are then produced. The data demonstrate that EGF‐FTH1 nanoparticles, with a small size (11.8 ± 1.8 nm), narrow size distribution, and high biosafety, can specifically bind to and then be taken up by breast cancer MCF‐7 cells and MDA‐MB‐231 cells, but not normal breast epithelial MCF‐10A cells. In contrast, binding and absorption of nontargeted ferritin‐based nanoparticles to breast cancer cells are negligible. In vivo studies show that EGF‐FTH1 nanoparticles are accumulated in breast tumors in a mouse xenograft model. Interestingly, the concentration of EGF‐FTH1 nanoparticles in the tumor site is significantly reduced when mice are pretreated with an excess of free EGF. These results imply that EGF–EGFR interaction plays an important role in regulating the tumor retention of EGF‐FTH1 nanoparticles.