Our group has designed a small molecule, non-peptidic, ligand that binds the cell surface receptor TrkC. This receptor is overexpressed on various types of tumors. A molecule 1   (IY-IY-PDT)was designed to contain a fragment (IY-IY) that targets the TrkC receptor, and a photosensitizer that acts as an agent for photodynamic therapy (PDT). Molecule 1  has sub-micromolar photocytotoxicities to cells that were either engineered to stably express TrkC (NIH3T3-TrkC) or that naturally express high levels of TrkC (SY5Y neuroblastoma, 4T1 murine breast cancer, and Hs578t human breast cancer lines). Control experiments showed 1  is not cytotoxic in the dark, and has significantly less photocytotoxicity towards cells that do not express TrkC. Another control featuring a scrambled agent 2  (YI-YI-PDT), isomeric with 1  , showed it is considerably less photocytotoxic than 1  on TrkC expressing cells. Our data illustrates the beneficial effects of targeting in cellular assays, including internalization of cargo agents and selective cell killing in vitro and in vivo.                                                    

Targeting TrkC expressing tumors in vitro and in vivo using a TrkC ligand conjugated to a BODIPY-based photodynamic therapy (PDT) agent

247th National Meeting (2014)

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