title: A novel peptide probe for imaging and targeted delivery of liposomal doxorubicin to lung tumor.
abstract: Targeted delivery of imaging agents and therapeutics to tumors would provide early detection and increased therapeutic efficacy against cancer. Here we have screened a phage-displayed peptide library to identify peptides that selectively bind to lung tumor cells. Evaluation of individual phage clones after screening revealed that a phage clone displaying the CSNIDARAC peptide bound to H460 lung tumor cells at higher extent than other phage clones. The synthetic CSNIDARAC peptide strongly bound to H460 cells and was efficiently internalized into the cells, while little binding of a control peptide was seen. It also preferentially bound to other lung tumor cell lines as compared to cells of different tumor types. In vivo imaging of lung tumor was achieved by homing of fluorescence dye-labeled CSNIDARAC peptide to the tumor after intravenous injection into mice. Ex vivo imaging and microscopic analysis of isolated organs further demonstrated the targeting of CSNIDARAC peptide to tumor. The CSNIDARAC peptide-targeted and doxorubicin-loaded liposomes inhibited the tumor growth more efficiently than untargeted liposomes or free doxorubicin. In vivo imaging of fluorescence dye-labeled liposomes demonstrated selective homing of the CSNIDARAC-liposomes to tumor. In the same context, higher levels of doxorubicin and apoptosis in tumor tissue were observed when treated with the targeted liposomes than untargeted liposomes or free doxorubicin. These results suggest that the CSNIDARAC peptide is a promising targeting probe that is able to direct imaging agents and therapeutics to lung tumor.
authors.affiliation: Department of Biochemistry and Cell Biology and Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-421, Korea.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: He
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Na
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Lee
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Allan S
authors.initials: AS
authors.lastname: Hoffman
authors.forename: Ju-Ock
authors.initials: JO
authors.lastname: Nam
authors.forename: Su-Eun
authors.initials: SE
authors.lastname: Han
authors.forename: Ga Yong
authors.initials: GY
authors.lastname: Sim
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019151:Peptide Library; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D010446:Peptide Fragments; D019151:Peptide Library; D004317:Doxorubicin