We first propose a simplified OM-pBAE formulation (pBAE-CRHR) with -CRHR sequence acting both as encapsulation enhancer and endosome escape promoter. To this core polymer, a zwitterionic (Zw) moiety was added as part of the end-capping process of the pBAE synthesis to form pBAE-CRHR-Zw. In addition to providing the stealth effect, zwitterionic-graft is expected to mask the excellent transfection potential of pBAEs, thereby preventing its non-specific cellular targeting. Subsequently, addition of a photo-cleavable zwitterionic-graft, enabled recovery of its on-site transfection capacity. Lastly, the pBAEs-CRHR-Zw were functionalized with BrainBike-4 (BB4), aiming to mediate cancer cell selectivity and blood-brain barrier (BBB) transport. BB4 is a bicyclic peptidomimetic recently developed in our lab, that binds transferrin receptor 1 (TfR1) . Aligning with our hypothesis, polyplexes derivatized with BB4 display high transfection capacity in cells overexpressing TfR1. Moreover, we demonstrated that the pBAE-CRHR-Zw polyplexes functionalized with BB4 could significantly enhance transport across a human cellbased model of the BBB.