Efficacious Anticancer Drug Delivery Mediated by a pH-Sensitive Self-Assembly of a Conserved Tripeptide Derived from Tyrosine Kinase NGF Receptor

Moitra, Parikshit and Kumar, Krishan and Kondaiah, Paturu and Bhattacharya, Santanu (2014) Efficacious Anticancer Drug Delivery Mediated by a pH-Sensitive Self-Assembly of a Conserved Tripeptide Derived from Tyrosine Kinase NGF Receptor. In: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 53 (4). pp. 1113-1117.

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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 pH7.4 but rupture rapidly at pH approximate to 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.

Item Type:	Journal Article
Publication:	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Publisher:	WILEY-V C H VERLAG GMBH
Additional Information:	Copyright for this article belongs to the WILEY-V C H VERLAG GMBH, GERMANY
Keywords:	drug delivery; nanostructures; peptides; pH sensitivity; self-assembly
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > Organic Chemistry
Date Deposited:	20 Feb 2014 11:21
Last Modified:	20 Feb 2014 11:21
URI:	http://eprints.iisc.ac.in/id/eprint/48417

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