Advertisement

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

Authors


  • NGF = Nerve growth factor. This work was supported by the J. C. Bose Fellowship grant of the Department of Science and Technology to S.B. Doxorubicin-resistant HeLa cells were a kind gift from Dr. Annapoorni Rangarajan. We thank the Chemical Sciences Division for the transmission electron microscopy facility.

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.

Ancillary