Folate receptor-mediated Therapeutics and Imaging

Abstract

Cancer is the second leading cause of death globally. Before a probable treatment approach is adopted based on early-stage diagnosis, there is a requirement for specific constructive and efficacious strategies. Identifying solid tumors through targeted detection of cancerous cells is one of the most reliable approaches to treatment. Over the past decade, the investigation of folate receptors (FR) has led to the development of several novel cancer treatments. Many tumor types exhibit high overexpression of FR, which was found to be associated with tumor progression and prognosis. Monitoring FR expression levels can prove a useful criterion as it is correlated with the advancement and prognosis of tumors. Due to the strong affinity of the FR towards folate and folate-conjugates, it can be designated as a tumor-associated antigen that is involved in the active transportation of the bound cargo within cells through an endocytic process. A wide range of payloads, from tiny radioactive imaging agents up to massive DNA-containing formulations, may be delivered to FR-positive cells using folate or an analog of it as the ligand. The FR targeting anticancer therapies are being developed currently and the response-predictive aspect of FR expression could serve as a biomarker for these treatments. By boosting delivery to the target tissue as well as an improved target-non-target tissue ratio, targeted drug delivery systems aim to increase the therapeutic windows of molecules. In turn, this results in a decreased minimum effective dose of the drug, lower drug toxicity, and improved treatment efficacy at comparable plasma concentrations. Targeted delivery is especially appealing for drugs with small therapeutic windows and/or those activated at very low concentrations due to the few targeted receptor sites on the specified target tissue. This review discusses recent developments in FR-mediated targeting for therapeutics and its applications in imaging, as well as highlights their potential and anticipated challenges.