Colloidal virus-like nanoparticles for targeted delivery of doxorubicin to non-small cell lung cancer using a cell-internalizing peptide.

Non-small cell lung cancer (NSCLC) is among the deadliest cancers globally. While chemotherapy is the most common treatment for NSCLC, its non-specific distribution to normal cells often leads to severe side effects. To overcome this limitation, cell internalizing peptides (CIPs) present a promising strategy for delivering chemotherapeutics directly to NSCLC cells, potentially improving patients' quality of life. In the present study, a novel CIP with the sequence IAQGASTPNQLR that internalized NSCLC was isolated from a phage-displayed peptide library using subtraction biopanning. This peptide demonstrated preferential internalization into lung adenocarcinoma cells via an active endocytosis pathway. Nanoglue and chemical crosslinkers were used to display the CIP on the surface of colloidal virus-like particles (VLPs) loaded with doxorubicin (Dox). These Dox-loaded VLPs were delivered specifically to lung adenocarcinoma cells by the CIP, significantly reducing non-specific toxicity to normal lung fibroblast cells. The present study highlights the potential of colloidal VLPs displaying the CIP for targeted delivery of chemotherapeutic agents to NSCLC cells.