title: Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active targeting.
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.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai 200237, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Lihui
authors.initials: L
authors.lastname: Qiu
authors.forename: Pei
authors.initials: P
authors.lastname: Zhu
authors.forename: Xinyi
authors.initials: X
authors.lastname: Tao
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Imanaka
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Youguo
authors.initials: Y
authors.lastname: Huang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Tu
authors.forename: Xuni
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004815:Epidermal Growth Factor / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000009:adverse effects / Q000627:therapeutic use* / Q000648:ultrastructure; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification; D012542:Scattering, Radiation; D023041:Xenograft Model Antitumor Assays
chemical_list: D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D001052:Apoferritins