Coumarin–benzothiazole–chlorambucil (Cou–Benz–Cbl) conjugate: an ESIPT based pH sensitive photoresponsive drug delivery system

Abstract

We have developed an ESIPT based drug delivery system (DDS), Cou–Benz–Cbl conjugate, by incorporating a benzothiazole group at the 8th position of the 7-hydroxy-coumarin moiety for pH sensitive fluorescence properties and photocontrolled release of the anticancer drug chlorambucil. The Cou–Benz–Cbl conjugate exhibited unique photophysical properties like good absorbance at around 350 nm, a large Stokes shift (∼151 nm) and pH sensitive fluorescence properties. The pH sensitive fluorescence properties of the Cou–Benz–Cbl conjugate can be ascribed to an ESIPT turn “on and off” mechanism. At physiological pH, the ESIPT gets turned “off” and a blue fluorescence of the coumarin moiety was observed, but at acidic pH, the ESIPT gets turned “on” and a green fluorescence was noted. Photolysis of the Cou–Benz–Cbl conjugate using UV light of wavelength ≥365 nm resulted in the efficient release of the anticancer drug chlorambucil. Cellular uptake studies revealed that the Cou–Benz–Cbl conjugate was easily internalized inside the cancer cells. Further, an MTT assay showed that the Cou–Benz–Cbl conjugate has a good biocompatibility and low cytotoxicity towards the MDA-MB-231 cell line, whereas upon exposure to UV light, the Cou–Benz–Cbl conjugate exhibited enhanced cytotoxicity compared to the free drug due to the effective release of the anticancer drug chlorambucil inside the cancer cell.