title: Peptide-mediated liposomal Doxorubicin enhances drug delivery efficiency and therapeutic efficacy in animal models.
abstract: Lung cancer ranks among the most common 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. In this study, we investigated the targeting mechanism of the ligand-mediated drug delivery system using a peptide, SP5-2, which specifically binds to non-small cell lung cancer (NSCLC) cells. Conjugation of SP5-2 to liposomes enhanced the amount of drug delivered directly into NSCLC cells, through receptor-mediated endocytosis. Functional SP5-2 improved the therapeutic index of Lipo-Dox by enhancing therapeutic efficacy, reducing side effects, and increasing the survival rate of tumor-bearing mice in syngenic, metastatic and orthotopic animal models. Accumulation of SP5-2-conjugated liposomal doxorubicin (SP5-2-LD) in tumor tissues was 11.2-fold higher than that of free doxorubicin, and the area under the concentration-time curve (AUC0-72 hours) was increased 159.2-fold. Furthermore, the experiment of bioavailability was assessed to confirm that SP5-2 elevates the uptake of the liposomal drugs by the tumor cells in vivo. In conclusion, the use of SP5-2-conjugated liposomes enhances pharmacokinetic properties, improves efficacy and safety profiles, and allows for controlled biodistribution and drug release.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: De-Kuan
authors.initials: DK
authors.lastname: Chang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Pi-Chun
authors.initials: PC
authors.lastname: Li
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Ruei-Min
authors.initials: RM
authors.lastname: Lu
authors.affiliation: Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Wann-Neng
authors.initials: WN
authors.lastname: Jane
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Han-Chung
authors.initials: HC
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin