We have recently developed a new class of bicyclic TfR1 binding peptidomimetics dubbed BrainBikes . Particularly, BrainBike-4 (BB4) has high affinity for cells with high levels of TfR1 expression (apparent KD∼40 nM) and high resistance to proteases, with a 5.5 h half-life in human serum, enabling enhanced targeting capacity . Therefore, we aim to derivatize the zwitterionic pBAE-CRHR-NB-Zw with BB4 to form polyplexes with high affinity towards cancer cells overexpressing TfR1.