title: Single chain anti-c-Met antibody conjugated nanoparticles for in vivo tumor-targeted imaging and drug delivery.
abstract: Aberrantly expressed c-Met, the receptor for hepatocyte growth factor (HGF), has been implicated in human lung cancer as well as malignancy, metastasis and drug-resistance in other human cancers. Thus, this molecule could be a potential target for antibody-based cancer therapy. Targeting delivery of compound to tumor represented benefit for cancer detection and therapy. In this study, we utilized phage display to identify human single chain variable fragment (scFv) antibodies that specifically bound to c-Met protein. The anti-c-Met scFvs selectively bound to and internalized in several lung cancer cell lines expressing c-Met. Conjugation of anti-c-Met scFv with PEGylated liposomes enabled the efficient delivery of doxorubicin into cancer cells where it exerted cytotoxic activity by inducing apoptosis pathway. In addition, in vivo fluorescent imaging by scFv-conjugated quantum dots showed higher tumor uptake and increased tumor-normal tissue ratios. In a tumor xenograft model, anti-c-Met immunoliposome was found to selectively increase tumor accumulation of a chemotherapeutic drug and enhance its antitumor activity. Taken together, our results suggest that anti-c-Met scFv-mediated drug delivery systems show great promise in tumor-targeted therapy and imaging.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Ruei-Min
authors.initials: RM
authors.lastname: Lu
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Chang
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Chen
authors.forename: Han-Chung
authors.initials: HC
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008175:Lung Neoplasms / Q000628:therapy; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects; D019151:Peptide Library; D011485:Protein Binding / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D019151:Peptide Library; D057127:Single-Chain Antibodies; D004317:Doxorubicin; D019859:Proto-Oncogene Proteins c-met