Switch off/switch on regulation of drug cytotoxicity by conjugation to a cell targeting peptide

Bi-nuclear amino acid platforms loaded with various drugs for conjugation to a peptide carrier were synthesized using simple and convenient orthogonally protective solid-phase organic synthesis (SPOS). Each arm of the platform carries a different anticancer agent linked through the same or different functional group, providing discrete chemo- and bio-release profiles for each drug, and also enabling switch off/switch on regulation of drug cytotoxicity by conjugation to the platform and to a cell targeting peptide. The versatility of this approach enables efficient production of drug-loaded platforms and determination of favorable drug combinations/modes of linkage for subsequent conjugation to a carrier moiety for targeted cancer cell therapy. The results presented here potentiate the application of amino acid platforms for targeted drug delivery (TDD). (C) 2014 Elsevier Masson SAS. All rights reserved.