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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
Author(s) -
Moitra Parikshit,
Kumar Krishan,
Kondaiah Paturu,
Bhattacharya Santanu
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201307247
Subject(s) - chemistry , vesicle , tripeptide , tyrosine kinase , biophysics , confocal microscopy , drug delivery , tyrosine kinase inhibitor , biochemistry , peptide , receptor , biology , microbiology and biotechnology , membrane , genetics , organic chemistry , cancer
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.