Folate receptor-targeted nanoprobes for molecular imaging of cancer: Friend or foe?

Abstract Molecular imaging (MI) of cancer is an emerging field in diagnostic imaging that provides means for visualization, characterization, and quantification of cancer biology in vivo. Various targeted nanoprobes (NPs) have been introduced to enhance signal and/or contrast, binding avidity, and targeting specificity for early detection of cancer. The overexpressed pattern of folate receptors (FRs) on the surface of cancer cells is overall distinct from normal cells. Therefore, folic acid (FA) or folate-conjugated NPs have gained much interest as diagnostic agents, therapeutics, and their combined use as theranostics for targeting FR-overexpressing tumor cells. A major advantage of FR-specific MI approaches is the high affinity of the ligand and its receptor. NPs can be designed for various clinical imaging modalities, including magnetic resonance imaging, computed tomography, optical and nuclear imaging, and ultrasonography. However, aside from the presence of high FR numbers in the normal kidney, a major challenge is the high non-specific uptake of both FA-targeted and non-targeted NPs in the liver and spleen, as evidenced by the lack of clinical trials using FA-NPs. This article summarizes the recent advancements that have been made with FR-specific MI methods and discusses the challenges for future clinical translation of FA-conjugated NPs.