Epidermal Growth Factor-Ferritin H-Chain Protein Nanoparticles for Tumor Active Targeting

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2012-08, Vol.8 (16), p.2505-2514
• Main Authors: Li, Xu, Qiu, Lihui, Zhu, Pei, Tao, Xinyi, Imanaka, Tadayuki, Zhao, Jing, Huang, Youguo, Tu, Yaping, Cao, Xuni
• Format: Article
• Language: English
• Subjects: Animals; Apoferritins - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Drug Delivery Systems - methods; epidermal growth factor; Epidermal Growth Factor - therapeutic use; Female; ferritin H-chain; Flow Cytometry; Humans; Light; Mice; Mice, Inbred BALB C; Mice, Nude; nanoparticles; Nanoparticles - adverse effects; Nanoparticles - therapeutic use; Nanoparticles - ultrastructure; Protein Binding; protein structures; Recombinant Fusion Proteins - isolation & purification; Scattering, Radiation; tumor targeting; Xenograft Model Antitumor Assays
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201200066

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. Epidermal growth factor (EGF)–human ferritin H‐chain protein (FTH1) nanoparticles are prepared by using a genetic method. The EGF‐FTH1 nanoparticles show a precisely assembled nanometer‐scale structure, and small size with narrow size distribution. Due to specific binding to EGF receptor (EGFR)‐positive cancer cells and the enhanced permeability and retention effect, in vivo tumor accumulation is observed.