title: Inhibition of pulmonary cancer progression by epidermal growth factor receptor-targeted transfection with Bcl-2 and survivin siRNAs.
abstract: Clinical application of small interfering RNA (siRNA) in cancer therapy has been limited by the lack of an efficient systemic siRNA delivery system. In this report we describe an efficient siRNA delivery system directed to metastasized tumors, especially in the lungs. Anticancer siRNA was condensed in the presence of 9-arginine peptides (9Arg) and then complexed with cationic O,O'-dimyristyl-N-lysyl glutamate liposomes conjugated to antibodies against the epidermal growth factor receptor (EGFR). The ternary complex of optimized anti-EGFR-9Arg-lipoplexes exhibited efficient siRNA transfection of LS174T-Luc cancer cells grown in culture or orthotopically in mouse lungs. Anti-tumor Bcl-2/survivin siRNAs loaded in the anti-EGFR-9Arg-lipoplexes effectively suppressed transcription of their target genes, resulting in an efficient cancer cell death. Repeated intravenous administrations of the anti-EGFR-9Arg-lipoplexes effectively inhibited tumor growth in the mouse lungs and prolonged survival of the mice compared with nontargeted lipoplexes. These results suggest that the ternary complexes of anti-EGFR-9Arg-lipoplexes might have clinical applications in RNA interference cancer therapy.
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Y K
authors: YK
authors: Lee
authors: Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Science (KIRAMS), Seoul, Republic of Korea.
authors: T S
authors: TS
authors: Lee
authors: 1] Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea [2] Department of Molecular Imaging Research Center, Korea Institute of Radiological and Medical Science (KIRAMS), Seoul, Republic of Korea.
authors: I H
authors: IH
authors: Song
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: H Y
authors: HY
authors: Jeong
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: S J
authors: SJ
authors: Kang
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: M W
authors: MW
authors: Kim
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: S H
authors: SH
authors: Ryu
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: I H
authors: IH
authors: Jung
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: J S
authors: JS
authors: Kim
authors: Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
authors: Y S
authors: YS
authors: Park
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D011859:Radiography; D000077022:Survivin; D014162:Transfection
chemical_list: C000595707:BCL2 protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D000077022:Survivin; D066246:ErbB Receptors