UC San Diego

The WNT signaling pathway plays an important role in embryonic development and adult tissue homeostasis. However, cancer cells often can use this pathway to acquire ‘stem-cell like’ properties aiding proliferation, self-renewal and chemoresistance[1]. Several therapies targeting the WNT pathway have been developed successfully, but owing to adverse side-effects, many of these have not advanced through clinical trials[1]. Further, the WNT pathway’s pleiotropic nature and complexity across different cancer types, necessitates the development of precise and targeted therapies. Previous studies have found that the WNT receptor, Frizzled class receptor 7 (FZD7), shows elevated expression in several cancer types, making it a potential target for cancer therapies[4]. Lipid nanoparticles (LNPs) have been used in targeted cancer therapies for the diversity of payloads they can accommodate and their enhanced permeability and retention in tumor vasculature[16]. Thus, I propose that LNP enclosed anti-cancer payloads can be specifically delivered to FZD7 expressing tumor cells with the help of a targeting molecule. To that end, I have engineered a FZD7 targeting Single Chain Variable Fragment (F7-scFv) and tested lipid nanoparticles conjugated with the F7-scFv for their ability to bind to cells in a receptor dependent manner, to potentially be used to deliver anticancer therapeutics to tumors.