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      1. Author :
        Asai, T.; Matsushita, S.; Kenjo, E.; Tsuzuku, T.; Yonenaga, N.; Koide, H.; Hatanaka, K.; Dewa, T.; Nango, M.; Maeda, N.; Kikuchi, H.; Oku, N.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Bioconjug Chem
      6. Products :
      7. Volume :
        22
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, B16-F10-luc2, B16F10-luc2; Base Sequence; Cell Line, Tumor; Cholesterol/metabolism; Ethylenediamines/*chemistry; Fibrosarcoma/metabolism/pathology; Gene Silencing; Humans; Injections, Intravenous; Liposomes/administration & dosage/chemical; synthesis/*chemistry/pharmacokinetics; Male; Mice; Mice, Inbred BALB C; Molecular Imaging; Phosphoric Acid Esters/*chemistry; Polyethylene Glycols/chemistry; RNA, Small Interfering/genetics/*metabolism; Spectrophotometry, Infrared
      12. Abstract :
        Dicetyl phosphate-tetraethylenepentamine (DCP-TEPA) conjugate was newly synthesized and formed into liposomes for efficient siRNA delivery. Formulation of DCP-TEPA-based polycation liposomes (TEPA-PCL) complexed with siRNA was examined by performing knockdown experiments using stable EGFP-transfected HT1080 human fibrosarcoma cells and siRNA for GFP. An adequate amount of DCP-TEPA in TEPA-PCL and N/P ratio of TEPA-PCL/siRNA complexes were determined based on the knockdown efficiency. Then, the biodistribution of TEPA-PCL modified with poly(ethylene glycol) (PEG) was examined in BALB/c mice. As a result, TEPA-PCL modified with PEG6000 avoided reticuloendothelial system uptake and showed long circulation in the bloodstream. On the other hand, PEGylation of TEPA-PCL/siRNA complexes caused dissociation of a portion of the siRNA from the liposomes. However, we found that the use of cholesterol-conjugated siRNA improved the interaction between TEPA-PCL and siRNA, which allowed PEGylation of TEPA-PCL/siRNA complexes without siRNA dissociation. In addition, TEPA-PCL complexed with cholesterol-conjugated siRNA showed potent knockdown efficiency in stable luciferase-transfected B16-F10 murine melanoma cells. Finally, the biodistribution of cholesterol-conjugated siRNA formulated in PEGylated TEPA-PCL was examined by performing near-infrared fluorescence imaging in Colon26 NL-17 murine carcinoma-bearing mice. Our results showed that tumor targeting with siRNA via systemic administration was achieved by using PEGylated TEPA-PCL combined with active targeting with Ala-Pro-Arg-Pro-Gly, a peptide used for targeting angiogenic endothelium.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21361311
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10347