Bioconjugate Supramolecular Pd Metallacages Penetrate the Blood Brain Barrier and .

The biomedical application of discrete supramolecular metal-based structures, specifically self-assembled metallacages, is still an emergent field of study. Capitalizing on the knowledge gained in recent years on the development of 3-dimensional (3D) metallacages as novel drug delivery systems and agents, we explore here the possibility to target [PdL] cages (L = 3,5-bis(3-ethynylpyridine)phenyl ligand) to the brain. In detail, a new water-soluble homoleptic cage () tethered to a blood brain barrier (BBB)-translocating peptide was synthesized by a combination of solid-phase peptide synthesis (SPPS) and self-assembly procedures. The cage translocation efficacy was assessed by inductively coupled mass spectrometry (ICP-MS) in a BBB cellular model . Biodistribution studies of the radiolabeled cage [[TcO] ⊂ ] in the CD1 mice model demonstrate its brain penetration properties . Further DFT studies were conducted to model the structure of the [[TcO] ⊂ cage] complex. Moreover, the encapsulation capabilities and stability of the cage were investigated using the [ReO] anion, the "cold" analogue of [TcO], by H NMR spectroscopy. Overall, our study constitutes another proof-of-concept of the unique potential of supramolecular coordination complexes for modifying the physiochemical and biodistribution properties of diagnostic species.