Folate-mediated delivery of protein and peptide drugs into tumors

The membrane-bound folate receptor (FR) is overexpressed on a wide range of human cancers, such as those originating in ovary, lung, breast, endometrium, kidney and brain. The vitamin folic acid (FA) is a high affinity ligand of the FR, which retains its receptor binding properties when conjugated to other molecules. Consequently, folate mediated targeting has been successfully applied for the delivery of a wide variety of payloads, including protein toxins, immunotherapeutic agents, adenoviral vectors and radio-imaging agents to FR-positive cancers. These folatebearing delivery systems have exhibited major enhancements in cancer cell specificity and selectivity over their non-targeted counterparts. Hence, it is hopeful that this targeting strategy should lead to improvements in the safety and efficacy of anti cancer agents, resulting in an increased therapeutic advantage in the clinic. This chapter reviews the growing literature on folate-targeted drugs, with specific emphasis on the delivery of proteins and peptides to cancers.