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  • Title: A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveolar endocytic pathway.
    Author: Mudhakir D, Akita H, Tan E, Harashima H.
    Journal: J Control Release; 2008 Jan 22; 125(2):164-73. PubMed ID: 18054812.
    Abstract:
    In the present study, the cellular uptake and subsequent intracellular trafficking of liposomes was investigated, in which a novel peptide (IRQ), identified with in vivo phage display, was modified on the surface. Since the novel peptide IRQRRRR is rich in arginine, the cellular uptake mechanism was compared with octaarginine (R8)-modified liposomes, which are known to be taken up by cells via macropinocytosis. The uptake mechanism and intracellular trafficking of peptide-modified liposomes was determined by confocal laser scanning microscopy and flow cytometry analysis. Modification of the liposomal surface with the IRQ peptide (IRQ-Lip), induced internalization via a novel pathway-caveolar endocytosis-in parallel with clathrin-mediated endocytosis. Furthermore, the IRQ peptide stimulated escape from endocytic vesicles, leading to efficient gene silencing. When siRNA was condensed and encapsulated in an IRQ-modified multifunctional envelope-type nano-device (IRQ-MEND), transgene expression was reduced 52% with the fusogenic lipid, DOPE/CHEMS. This result shows that the novel IRQ can be utilized for cytoplasmic delivery of macromolecules. Moreover, the IRQ has the potential to be useful for delivery therapeutic agents to parenchymal cells via caveolar endocytosis, as this uptake pathway also plays an important role in transcytosis.
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