Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active targeting

Xu Li, Lihui Qiu, Pei Zhu, Xinyi Tao, Tadayuki Imanaka, Jing Zhao, Youguo Huang, Yaping Tu, Xuni Cao

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2505-2514
Number of pages10
JournalSmall
Volume8
Issue number16
DOIs
StatePublished - Aug 20 2012

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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    Li, X., Qiu, L., Zhu, P., Tao, X., Imanaka, T., Zhao, J., Huang, Y., Tu, Y., & Cao, X. (2012). Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active targeting. Small, 8(16), 2505-2514. https://doi.org/10.1002/smll.201200066