In vivo fluorescence imaging for cancer diagnosis using receptor-targeted epidermal growth factor-based nanoprobe
- In vivo fluorescence imaging for cancer diagnosis using receptor-targeted epidermal growth factor-based nanoprobe
- 류주희; 신미영; 김선아; 이상민; 김현준; 구희범; 김병수; 송현규; 김선화; 최귀원; 권익찬; 전혜성; 김광명
- Epidermal growth factor receptor (EGFR); EGF-based nanoprobe; Cancer imaging; Receptor-targeted imaging; Epidermal growth factor (EGF)
- Issue Date
- VOL 34, NO 36, 9149-9159
- 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.
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