Three-arm, biotin-tagged carbazole-dicyanovinyl-chlorambucil conjugate: simultaneous tumor targeting, sensing, and photoresponsive anticancer drug delivery

Abstract

The design, synthesis and in vitro biological studies of a biotin-carbazole-dicyanovinyl-chlorambucil conjugate (Bio-CBZ-DCV-CBL; 6) are reported. This conjugate (6) is a multifunctional single-molecule appliance composed of a thiol-sensor DCV functionality, a CBZ-derived phototrigger as well as fluorescent reporter and CBL as the anticancer drug and Bio as the cancer-targeting ligand. In conjugate 6, the DCV bond undergoes a thiol-ene click reaction at pH<7 with intracellular thiols, thereby shutting down internal charge transfer between the donor CBZ and acceptor DCV units, resulting in a change of the fluorescence color from green to blue, and thereby, sensing the tumor microenvironment. Subsequent photoirradiation results in release of the anticancer drug CBL in a controlled manner.