title: Enhanced In Vivo Tumor Detection by Active Tumor Cell Targeting Using Multiple Tumor Receptor-Binding Peptides Presented on Genetically Engineered Human Ferritin Nanoparticles.
abstract: Human ferritin heavy-chain nanoparticle (hFTH) is genetically engineered to present tumor receptor-binding peptides (affibody and/or RGD-derived cyclic peptides, named 4CRGD here) on its surface. The affibody and 4CRGD specifically and strongly binds to human epidermal growth factor receptor I (EGFR) and human integrin αvβ3, respectively, which are overexpressed on various tumor cells. Through in vitro culture of EGFR-overexpressing adenocarcinoma (MDA-MB-468) and integrin-overexpressing glioblastoma cells (U87MG), it is clarified that specific interactions between receptors on tumor cells and receptor-binding peptides on engineered hFTH is critical in active tumor cell targeting. After labeling with the near-infrared fluorescence dye (Cy5.5) and intravenouse injection into MDA-MB-468 or U87MG tumor-bearing mice, the recombinant hFTHs presenting either peptide or both of affibody and 4CRGD are successfully delivered to and retained in the tumor for a prolonged period of time. In particular, the recombinant hFTH presenting both affibody and 4CRGD notably enhances in vivo detection of U87MG tumors that express heterogeneous receptors, integrin and EGFR, compared to the other recombinant hFTHs presenting either affibody or 4CRGD only. Like affibody and 4CRGD used in this study, other multiple tumor receptor-binding peptides can be also genetically introduced to the hFTH surface for actively targeting of in vivo tumors with heterogenous receptors.
authors.affiliation: Department of Chemical and Biological Engineering, College of Engineering, Korea University, Anam-Ro 145, Seoul, 136-713, South Korea.
authors.forename: Koo Chul
authors.initials: KC
authors.lastname: Kwon
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, South Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 151-742, South Korea.
authors.forename: Ho Kyung
authors.initials: HK
authors.lastname: Ko
authors.affiliation: Department of Chemical and Biological Engineering, College of Engineering, Korea University, Anam-Ro 145, Seoul, 136-713, South Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, South Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, South Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Chemical and Biological Engineering, College of Engineering, Korea University, Anam-Ro 145, Seoul, 136-713, South Korea.
authors.forename: Jeewon
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D005293:Ferritins / Q000737:chemistry*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D039302:Integrin alphaVbeta3; D010455:Peptides; D005293:Ferritins
keywords: active tumor targeting; human ferritin; in vivo tumor detection; multiple tumor receptor-binding peptides; surface engineering