Synthetic zipper mediated pre-targeting system for near-infrared photoimmunotherapy

Several strategies have gained attraction in cancer diagnosis and therapy, particularly to overcome the limitations associated with direct targeting approaches in radioimmunotherapy and photoimmunotherapy. Here, we have introduced a synthetic zipper-mediated pre-targeting system for near-infrared photoimmunotherapy (NIR-PIT) utilizing the IR700-conjugated Zip1-SNAP protein in combination with three scFv-ZIP2 fusion proteins targeting FOLR1, TROP2, and TF. In this two-step targeting approach, scFv-Zip2 proteins first bind to cancer-specific antigens, followed by hybridization with Zip1-SNAP-IR700 at cell surface via high-affinity zipper interaction. Upon NIR light irradiation, targeted cancer cells underwent selective phototoxicity in a concentration-dependent manner with IC(50) range (

• Mohiuddin, T. M.
• Zhang, C.
• Sheng, W.
• Al-Rawe, M.
• El-Merhie, N.
• Zeppernick, F.
• Meinhold-Heerlein, I.
• Hussain, A. F.