Uroguanylin-decorated Nanosystems Containing Etoposide, a Potential Targeted Combination Therapy for Colorectal Cancer

Abstract

Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Guanylyl Cyclase C (GCC), a membrane receptor that is expressed in 95% of primary and metastatic colorectal cancer tumors is a promising target for the design of new drug delivery strategies. In this work we propose the use of Uroguanylin (UroG), a natural ligand for GCC, for the preparation of targeted sphingomyelin-based nanosystems (UroG-SNs). The results from in vitro cell culture studies showed that UroG-SNs have a specific interaction with the GCC receptor, resulting in an antiproliferative response. Subsequently, the anti-cancer drug etoposide (Etp) was encapsulated into the UroG-SNs. The evaluation of the resulting system showed a synergistic effect of the two drugs, thus highlighting the therapeutic potential of this strategy for the treatment of colorectal cancer.