Molecular Delivery of Cytotoxic Agents via Integrin Activation

SIMPLE SUMMARY: Chemotherapy constituted a cornerstone in cancer treatment, but it suffers from non-selective drug cytotoxicity; an active drug targeting exerted by covalent conjugates between antitumor agents and some integrin ligands should have a more selective antitumor efficacy and could be an effective answer to reduce intolerable side-effects of current therapies. In this review we focused on those cytotoxic agents that were covalently inserted in molecular cargos characterized by specific integrin ligands. It was demonstrated that the integrin recognizing fragments were able to switch on an active and selective targeting against tumor cells. ABSTRACT: Integrins are cell adhesion receptors overexpressed in tumor cells. A direct inhibition of integrins was investigated, but the best inhibitors performed poorly in clinical trials. A gained attention towards these receptors arouse because they could be target for a selective transport of cytotoxic agents. Several active-targeting systems have been developed to use integrins as a selective cell entrance for some antitumor agents. The aim of this review paper is to report on the most recent results on covalent conjugates between integrin ligands and antitumor drugs. Cytotoxic drugs thus conjugated through specific linker to integrin ligands, mainly RGD peptides, demonstrated that the covalent conjugates were more selective against tumor cells and hopefully with fewer side effects than the free drugs.