title: In vivo fluorescence imaging for cancer diagnosis using receptor-targeted epidermal growth factor-based nanoprobe.
abstract: Receptor-targeted imaging is emerging as a promising strategy for diagnosis of human cancer. Herein, we developed an epidermal growth factor-based nanoprobe (EGF-NP) for in vivo optical imaging of epidermal growth factor receptor (EGFR), an important target for cancer imaging. The self-quenched EGF-NP is fabricated by sequentially conjugating a near-infrared (NIR) fluorophore (Cy5.5) and a quencher (BHQ-3) to EGF, a low-molecular weight polypeptide (6.2 kDa), compared to EGFR antibody (150 kDa). The self-quenched EGF-NP presented great specificity to EGFR, and rapidly internalized into the cells, as monitored by time-lapse imaging. Importantly, the self-quenched EGF-NP boosted strong fluorescence signals upon EGFR-targeted uptake into EGFR-expressing cells, followed by lysosomal degradation, as confirmed by lysosomal marker cell imaging. Consistent with cellular results, intravenous injection of EGF-NP into tumor-bearing mice induced strong NIR fluorescence intensity in the target tumor tissue with high specificity against EGFR-expressing cancer cells. Signal accumulation of EGF-NP in tumor was much faster than that of EGFR monoclonal antibody (Cetuximab)-Cy5.5 conjugates due to the rapid clearance from the body and tissue permeability of low-molecular weight EGF. This self-quenched, EGF-based imaging probe can be applied for diagnosis of various cancers.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea; School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-744, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Ryu
authors.forename: Miyoung
authors.initials: M
authors.lastname: Shin
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Kim
authors.forename: Sangmin
authors.initials: S
authors.lastname: Lee
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kim
authors.forename: Heebeom
authors.initials: H
authors.lastname: Koo
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Hyun Kyu
authors.initials: HK
authors.lastname: Song
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Hyesung
authors.initials: H
authors.lastname: Jeon
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D004815:Epidermal Growth Factor; D066246:ErbB Receptors / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms / Q000175:diagnosis*; D019265:Spectroscopy, Near-Infrared
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: Cancer imaging; EGF-based nanoprobe; Epidermal growth factor (EGF); Epidermal growth factor receptor (EGFR); Receptor-targeted imaging