title: Development of Rous sarcoma Virus-like Particles Displaying hCC49 scFv for Specific Targeted Drug Delivery to Human Colon Carcinoma Cells.
abstract: OBJECTIVE
  Virus-like particles (VLPs) have been used as drug carriers for drug delivery systems. In this study, hCC49 single chain fragment variable (scFv)-displaying Rous sarcoma virus-like particles (RSV VLPs) were produced in silkworm larvae to be a specific carrier of an anti-cancer drug.
  
  
  METHODS
  RSV VLPs displaying hCC49 scFv were created by the fusion of the transmembrane and cytoplasmic domains of hemagglutinin from influenza A (H1N1) virus and produced in silkworm larvae. The display of hCC49 scFv on the surface of RSV VLPs was confirmed by enzyme-linked immunosorbent assay using tumor-associated glycoprotein-72 (TAG-72), fluorescent microscopy, and immunoelectron microscopy. Fluorescein isothiocyanate (FITC) or doxorubicin (DOX) was incorporated into hCC49 scFv-displaying RSV VLPs by electroporation and specific targeting of these VLPs was investigated by fluorescent microscopy and cytotoxicity assay using LS174T cells.
  
  
  RESULTS
  FITC was delivered to LS174T human colon adenocarcinoma cells by hCC49 scFv-displaying RSV VLPs, but not by RSV VLPs. This indicated that hCC49 scFv allowed FITC-loaded RSV VLPs to be delivered to LS174T cells. DOX, which is an anti-cancer drug with intrinsic red fluorescence, was also loaded into hCC49 scFv-displaying RSV VLPs by electroporation; the DOX-loaded hCC49 scFv-displaying RSV VLPs killed LS174T cells via the specific delivery of DOX that was mediated by hCC49 scFv. HEK293 cells were alive even though in the presence of DOX-loaded hCC49 scFv-displaying RSV VLPs.
  
  
  CONCLUSIONS
  These results showed that hCC49 scFv-displaying RSV VLPs from silkworm larvae offered specific drug delivery to colon carcinoma cells in vitro. This scFv-displaying enveloped VLP system could be applied to drug and gene delivery to other target cells.
authors.affiliation: Laboratory of Biotechnology, Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan.|Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan.|Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.affiliation: Laboratory of Biotechnology, Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yui
authors.affiliation: Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan.
authors.forename: Vipin Kumar
authors.initials: VK
authors.lastname: Deo
authors.affiliation: Laboratory of Biotechnology, Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan. park.enoch@shizuoka.ac.jp.|Graduate School of Science and Technology, Shizuoka University, 836 Ohya, Shizuoka, 422-8529, Japan. park.enoch@shizuoka.ac.jp.|Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529, Japan. park.enoch@shizuoka.ac.jp.
authors.forename: Enoch Y
authors.initials: EY
authors.lastname: Park
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D012831:Bombyx / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D015683:Gene Products, gag / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007814:Larva / Q000235:genetics; D052736:Rous sarcoma virus / Q000235:genetics* / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000235:genetics*; D058425:Vaccines, Virus-Like Particle / Q000235:genetics; D014771:Virion / Q000235:genetics* / Q000378:metabolism
chemical_list: D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; C091202:B72.3 antibody; D004337:Drug Carriers; D015683:Gene Products, gag; D057127:Single-Chain Antibodies; D058425:Vaccines, Virus-Like Particle
keywords: Rous sarcoma virus-like particles; colon carcinoma; doxorubicin; drug delivery; silkworm