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Abstract
The lack of molecular targets and targeting probes remains a major drawback for targeted imaging and drug delivery in lung cancer. In this study, we exploited in vivo phage display to identify a novel targeting probe that homes to the tumor in a K-rasLA2 mutant mouse lung cancer model. Compared with other candidate peptides selected from five rounds of phage display, the CRQTKN peptide homed to tumor nodules in the lung of mutant mice at higher levels. Photoacoustic tomography of mutant mice detected lung tumors via tumor homing of the near-infrared fluorescence dye-labeled CRQTKN peptide. Ex vivo photoacoustic images of isolated organs further demonstrated tumor homing of the CRQTKN peptide, while minimal accumulation was observed in control organs, such as the liver. Compared with untargeted liposomes and doxorubicin, doxorubicin-loaded liposomes whose surface was modified with the CRQTKN peptide more efficiently delivered doxorubicin and reduced the number or size of tumor lesions in K-rasLA2 mutant mice. Analysis of hematologic parameters and liver and kidney function showed no significant systemic side effects by the treatments. Affinity-based identification was used to detect tumor necrosis factor receptor superfamily member 19L (TNFRSF19L), which was up-regulated in lung tumors of mutant mice, as the receptor for the CRQTKN peptide. In conclusion, these results suggest that the CRQTKN peptide is a promising targeting probe for photoacoustic-guided detection and drug delivery to lung cancer, and acts by binding to TNFRSF19L.

Author information

Jung H1, Park S2, Gunassekaran GR3, Jeon M4, Cho YE5, Baek MC5, Park JY6, Shim G7, Oh YK7, Kim IS8, Kim C9, Lee B10.
1
Molecular and Cellular Biology, UIUC.
2
Institute of Advanced Convergence Technology, Kyungpook National University.
3
Department of Biochemistry and Cell Biology, Kyungpook National University.
4
Kyungpook National University.
5
Molecular Medicine, School of Medicine, Kyungpook National University.
6
Lung Cancer Center, Kyungpook National University.
7
Pharmacy, Seoul National University.
8
Center for Theragnosis, Biomedical Research Institute, Korea Institute Science and Technology.
9
IT Engineering, Pohang University of Science and Technology.
10
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University leebh@knu.ac.kr.