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

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.