The peptide-Au clusters inhibit EGFR exon 19 deletion mutant non-small cell lung cancer

Abstract

Epidermal growth factor receptor (EGFR) exon 19 deletions are a common mutation that can lead to non-small cell lung cancer (NSCLC). Here, we designed and synthesized Au clusters coated with EGFR-target peptides to treat EGFR exon 19 deletions mutated NSCLC. Two sequences of peptides (namely P1 and P2 peptide) were designed for synthesis two Au clusters (namely P1-Au and P2-Au), respectively. These two clusters specifically target the extracellular region of EGFR and enter cancer cells through endocytosis. ICP-MS measurements, enzyme activity experiments and cytotoxicity studies in H1650 cells (exon 19 deletions of EGFR) demonstrated that P1-Au clusters have stronger targeting ability towards EGFR, well inhibits EGFR phosphorylation and outcome a better anti-tumor effect than that of P2-Au clusters. Further experiments revealed that the P1-Au clusters enter H1650 cells through the clathrin-mediated endocytosis pathway, escape from lysosomes to the cytoplasm, and inhibit the phosphorylation of EGFR exon 19 deletions and its downstream protein to induce cancer cell apoptosis. P1-Au clusters significantly inhibited the tumor growth in an H1650 xenograft model via suppress EGFR exon 19 deletions mutant activation.