Novel peptides for targeted drug delivery for the treatment of non-small cell lung cancer

Despite the advances in treatment of cancer, new therapies are still needed. One reason for this is attributed to the heterogeneity of cancer. Such complexity results in tumors consisting of multiple cell subpopulations and needs to be treated with a combination of drugs each with a different mechanism of action. The development of peptide-based targeted medicines (PDCs) may help to improve the treatment addressing receptor mediated heterogeneity because of a mutagenesis in cancer cells. Cancer cells overexpress certain receptors essential for their survival and proliferation. PDC technology takes advantage of this phenomena, by exploiting molecular carriers as ligands to these overexpressed receptors in cancer cells. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we propose to utilize specific peptide drug carriers for drug delivery to lung cancer. First, we identified peptide ligands using phage display technology and bio-informatic tools in NSCLC H1299 cell lines. 11 peptides were selected and labeled with FITC. 3 peptides were found specific to the H1299 target cells (P6, P8, P9). These peptides showed minor binding to the off-target cell lines (K562 and HEK). This indicates specificity of the peptides to the target H1299 cell line. All tested peptides were not cytotoxic. To further investigate the potential of the peptide as a drug carrier, peptide drug conjugates were synthetized using DNA alkylator Chlorambucil and Topo I inhibitor Camptothecin as a payload. The comparative study in vitro found peptide drug conjugates more toxic and cell specific than the free drug after preincubation for 3 hours. The results indicate the potential of the selected peptides as a targeted drug delivery system to treat NSCLC.