Peptide-mediated liposomal doxorubicin enhances drug delivery efficiency and therapeutic efficacy in lung cancer animal models

摘要

[[abstract]]Background: Lung cancer ranks among the most commonly occurring malignancies, and is the leading cause of cancer-related mortality worldwide. Chemotherapy for lung cancer can be made more specific to tumor cells, and less toxic to normal tissues, through the use of ligand-mediated drug delivery systems.Methods: For the screening of targeting peptides, a phagedisplayed peptide library underwent affinity selection with lung cancer cells. Targeting phage clones were selected by ELISA, immunofluorescence, flow cytometry and an in vivo homing as says. Targeting peptides can be used to develop ligand-mediated targeted therapy or targeting imaging probe. For preclinical study, we evaluated therapeutic efficacy of targeting liposomes using xenograft, orthotopic- and metastatic-tumor animal models Results: In this study, we investigated the targeting mechanism of the ligand-mediated drug delivery system using lung cancer targeting peptides. Conjugation of lung cancer targeting peptides to liposomes enhanced the amount of drug delivered directly into NSCLC cells, through receptor-mediated endocytosis. Accumulation of peptide-conjugated liposomal doxorubicin (SP-LD) in tumor tissues was 11.2-fold higher than that of free doxorubicin, and the area unde the concentration-time curve (AUC0-72 hours) was increased 159.2-fold. Furthermore, SP-LD enhanced therapeutic efficacy and increased the survival rate of tumor-bearing mice in syngenic, metastatic and orthotopic animal models. Conclusion: The current study suggests that tumor-specific peptides may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC. The use of lung cancer targeting peptide-conjugated liposomes enhances pharmacokinetic properties, improves efficacy and safety profiles, and allows for controlled biodistribution and drug release.