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      Efficacious anticancer drug delivery mediated by a pH-sensitive self-assembly of a conserved tripeptide derived from tyrosine kinase NGF receptor.

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          Abstract

          We present herein a short tripeptide sequence (Lys-Phe-Gly or KFG) that is situated in the juxtamembrane region of the tyrosine kinase nerve growth factor (Trk NGF) receptors. KFG self-assembles in water and shows a reversible and concentration-dependent switching of nanostructures from nanospheres (vesicles) to nanotubes, as evidenced by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The morphology change was associated with a transition in the secondary structure. The tripeptide vesicles have inner aqueous compartments and are stable at pH 7.4 but rupture rapidly at pH≈6. The pH-sensitive response of the vesicles was exploited for the delivery of a chemotherapeutic anticancer drug, doxorubicin, which resulted in enhanced cytotoxicity for both drug-sensitive and drug-resistant cells. Efficient intracellular release of the drug was confirmed by fluorescence-activated cell sorting analysis, fluorescence microscopy, and confocal microscopy.

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          Author and article information

          Journal
          Angew. Chem. Int. Ed. Engl.
          Angewandte Chemie (International ed. in English)
          1521-3773
          1433-7851
          Jan 20 2014
          : 53
          : 4
          Affiliations
          [1 ] Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012 (India).
          Article
          10.1002/anie.201307247
          24338837
          Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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