Page - (000380) - in Biomedical Chemistry: Current Trends and Developments

(ACS, 2014; Kamaly, 2012; Moghimi, 2005). Folic acid has been one of the most employed and studied molecules among the numerous targeting ligands used in cancer targeted therapy, fundamentally due to its high affinity to the folate receptor (FR), which was found of being frequently overexpressed on many tumors, including ovarian, breast, brain, renal, colon and lung cancers (ACS, 2014; Annabi, 2014; Bachmann, 2010; Lee, 2011). Unfortunately, the FR expression seems to rely on inter-tumor variability and, therefore, the tumor predisposition for accumulating folate-targeted nanomedicines needs to be individually evaluated (Bachmann, 2010; Kamaly, 2012). Recently, folate-targeted imaging strategies have emerged for identifying FR-positive patients, permitting the selection of those that would in fact benefit from the administration of the folate-targeted nanoparticles (Bimbo, 2013). Interestingly, these images would possibly enable the quantification of the receptor displayed in the cellular surface and readily available to interact with the targeting ligand. Additionally to the tumor inter-variability of the FR overexpression, this receptor is also expressed in healthy tissues, a fact that might constitute a major downside on the administration of folate-targeted nanosystems for specific drug delivery to cancer. Definitively, a successful case on the field of tumor targeted therapy, particularly when a small molecule is used as a targeting moiety, is the one of BIND-014 (Table 3.5.3). This nanomedicine relies on the targeting affinity of a urea-based small molecule denominated S,S-2-[3-[5-amino-1- carboxypentyl]-ureido]-pentanedioic acid (ACUPA) to PSMA (Binjawadagi, 2014; Nembrini, 2011). Docetaxel-loaded nanoparticles with a ligand density of approximately 200 ACUPA molecules per particle exhibited an optimized targeting of PSMA-positive prostate tumors, with no visible change in the systemic circulation kinetics (Binjawadagi, 2014; Chen, 2012). Table 3.5.3: Tumor-targeted nanomedicines in clinical development. Adapted and reprinted with permission from (Bertrand, 2014).