RRC ID 37486
著者 Kato T, Yui M, Deo VK, Park EY.
タイトル Development of Rous sarcoma Virus-like Particles Displaying hCC49 scFv for Specific Targeted Drug Delivery to Human Colon Carcinoma Cells.
ジャーナル Pharm Res
Abstract PURPOSE: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.
METHOD: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.
CONCLUSION: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.
巻・号 32(11)
ページ 3699-707
公開日 2015-11-1
DOI 10.1007/s11095-015-1730-2
PII 10.1007/s11095-015-1730-2
PMID 26047779
MeSH Animals Antibodies, Neoplasm / genetics* Antineoplastic Agents / administration & dosage* Bombyx / genetics Cell Line, Tumor Cell Survival / drug effects Colonic Neoplasms / pathology Drug Carriers Drug Delivery Systems / methods* Gene Products, gag / metabolism HEK293 Cells Humans Larva / genetics Rous sarcoma virus / genetics* Rous sarcoma virus / metabolism Single-Chain Antibodies / genetics* Vaccines, Virus-Like Particle / genetics Virion / genetics* Virion / metabolism
IF 3.242
引用数 13
WOS 分野 PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY
リソース情報
ヒト・動物細胞 293(RCB1637)