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 language | English |
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Pages (from-to) | 2505-2514 |
Number of pages | 10 |
Journal | Small |
Volume | 8 |
Issue number | 16 |
DOIs | |
State | Published - Aug 20 2012 |
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All Science Journal Classification (ASJC) codes
- Biomaterials
- Engineering (miscellaneous)
- Biotechnology
- Medicine(all)
Cite this
Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active targeting. / Li, Xu; Qiu, Lihui; Zhu, Pei; Tao, Xinyi; Imanaka, Tadayuki; Zhao, Jing; Huang, Youguo; Tu, Yaping; Cao, Xuni.
In: Small, Vol. 8, No. 16, 20.08.2012, p. 2505-2514.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active targeting
AU - Li, Xu
AU - Qiu, Lihui
AU - Zhu, Pei
AU - Tao, Xinyi
AU - Imanaka, Tadayuki
AU - Zhao, Jing
AU - Huang, Youguo
AU - Tu, Yaping
AU - Cao, Xuni
PY - 2012/8/20
Y1 - 2012/8/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84864667428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864667428&partnerID=8YFLogxK
U2 - 10.1002/smll.201200066
DO - 10.1002/smll.201200066
M3 - Article
C2 - 22619186
AN - SCOPUS:84864667428
VL - 8
SP - 2505
EP - 2514
JO - Small
JF - Small
SN - 1613-6810
IS - 16
ER -