Research Papers:

One-bead one-compound combinatorial library derived targeting ligands for detection and treatment of oral squamous cancer

Fan Yang _, Wenwu Xiao, Yanlei Liu, Ruiwu Liu, Randall Kramer, Xiaocen Li, Yousif Ajena, Christopher M. Baehr, Tatu Rojalin, Hongyong Zhang and Kit S. Lam _

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Oncotarget. 2019; 10:5468-5479. https://doi.org/10.18632/oncotarget.27189

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Fan Yang1, Wenwu Xiao2, Yanlei Liu3, Ruiwu Liu2, Randall Kramer4, Xiaocen Li2, Yousif Ajena2, Christopher M. Baehr2, Tatu Rojalin2, Hongyong Zhang2 and Kit S. Lam2

1 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA

2 Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA

3 Department of Pathology, University of California Davis Medical Center, Sacramento, CA, USA

4 Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA

Correspondence to:

Fan Yang,email: [email protected]
Kit S. Lam,email: [email protected]

Keywords: oral squamous cancer; α3 integrin; optical imaging; cancer-targeting peptide; orthotopic xenograft model

Received: July 27, 2018     Accepted: August 12, 2019     Published: September 10, 2019


Oral squamous cancers (OSC) are hallmarked by poor prognosis, delayed clinical detection, and a lack of defined, characteristic biomarkers. By screening combinatorial one-bead one-compound (OBOC) peptide libraries against oral squamous cancer cell lines, two cyclic peptide ligands, LLY12 and LLY13 were previously identified. These ligands are capable of specific binding to the oral cancer cell lines (MOK-101, HSC-3, SCC-4 and SCC-10a) but not non-cancerous keratinocytes, leukocytes, fibroblast, and endothelial cells. These two peptides were synthesized and evaluated for their binding property, cytotoxicity and cell permeability. In vitro studies indicate that both LLY12 and LLY13 were able to bind to oral cancer cells with high specificity but did not show any cytotoxicity against human keratinocytes. Biotinylated LLY13, in complex with streptavidin-alexa488 was taken up by live oral cancer cells, thus rendering it as an excellent candidate vehicle for efficient delivery of drug loaded-nanoparticles. In vivo and ex vivo near infra-red fluorescence imaging studies confirmed the in vivo targeting efficiency and specificity of LLY13 in oral cancer orthotopic murine xenograft model. In vivo studies also showed that LLY13 was able to accumulate in the OSC tumors and demarcate the tumor margins in orthotopic xenograft model. Together, our data supports LLY13 as a promising theranostic agent against OSC.

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