Cancer-Cell-Specific Drug Delivery by a Tumor-Homing CPP-Gossypol Conjugate Employing a Tracelessly Cleavable Linker

Abstract

Tumor-targeted drug delivery is highly important for improving chemotherapy, as it reduces the dose of cytotoxic agents and minimizes the death of healthy tissues. Towards this goal, a conjugate was synthesized of gossypol and a MCF-7 cancer cell specific CPP (cell penetrating peptide), thus providing a selective drug delivery system. Utilizing the aldehyde moiety of gossypol, the tumor homing CPP RLYMRYYSPTTRRYG was attached through a semi-labile imine linker, which was cleaved in a traceless fashion under aqueous conditions and had a half-life of approximately 10 hours. The conjugate killed MCF-7 cells to a significantly greater extent than HeLa cells or healthy fibroblasts.

Keywords: cleavable linker; drug delivery; gossypol; imine linkage; tumor-homing peptide.