Prodrug Conjugate Strategies in Targeted Anticancer Drug Delivery Systems

Abstract

Chemotherapy is the mainstay in the treatment of various cancers for several decades; however, it suffers several clinical limitations. For example, anticancer drugs are often nonselective and are taken up by all forms of cells. Non-selectivity of the agents usually results in significant toxicity to normal cells, thus resulting in poor prognosis for patients. Hence, to improve the therapeutic efficacy of chemotherapy, improving the selectivity of anticancer drug is highly desired. Prodrug conjugation is one of the most beneficial strategies to enhance selectivity and efficacy of a chemotherapy drug. The classical prodrug approach is to overcome physicochemical (e.g., solubility, chemical instability) or biopharmaceutical problems (e.g., bioavailability, toxicity) associated with common anticancer drugs via a simple chemical modification. On the other hand, here we discuss targeted prodrug systems for delivering anticancer agents specifically to tumor cells, thereby sparing normal cells. This chapter focuses on various synthetic strategies in designing targeted prodrug conjugates and its rationale for cancer treatment. Various tumor-targeting ligands that are currently being explored are critically discussed.