Supramolecular self-assembly is a promising tool to develop multifunctional theranostic agents and has recently entered the field of radiochemistry.In this work,lantern-shaped[Pd_(2)L_(4)]^(4+)metallacages featuring a...Supramolecular self-assembly is a promising tool to develop multifunctional theranostic agents and has recently entered the field of radiochemistry.In this work,lantern-shaped[Pd_(2)L_(4)]^(4+)metallacages featuring a blood–brain barrier-penetrating peptide were designed for dual-modality imaging.Two silicon-based fluoride acceptors were incorporated in the cage ligand for radiolabeling with fluorine-18,an isotope used in positron emission tomography(PET).Ligands(L1,L2)and the respective homoleptic cages(C1hom[Pd_(2)(L1)_(4)]^(4+),C2hom[Pd_(2)(L2)_(4)]^(4+))were fully characterized by NMR spectroscopy,liquid chromatography and high-resolution electrospray mass spectrometry(HR-ESI-MS).Cage stability was assessed in different solvents and concentrations by HPLC.^(18)F-labelled cages were obtained by radiolabeling the ligands preassembly under mild conditions within four hours via[19F]-to-[^(18)F]isotopic exchange.The high lipophilicity of the ligands was also assessed in vitro(log DpH_(7.4))and in ovo,using the chick chorioallantoic membrane(CAM)model.Furthermore,formation of host–vip complexes between the metallacages and perrhenate(ReO_(4)^(-)),the‘cold’surrogate of radioactive^(99m)TcO_(4)-(used for single photon computed tomography,SPECT),could be detected by mass spectrometry,although the adduct did not sustain chromatographic separation.To improve stability of the supramolecular system,heteroleptic cages of general formula[Pd_(2)(L)m(L0)_(n)]^(4+)(m=1,2,n=4-m)were synthesized by statistical self-assembly and separated by liquid chromatography in good yield.Overall,this study demonstrates the feasible adaptation of supramolecular principles to achieve innovative theranostic agents.展开更多
基金funding from EU Horizon Europe Research and Innovation program,EIC Pathfinder Open network“SMARTdrugs”(grant agreement ID:101129886)Funding for T.H.W.was provided by UK Research and Innovation(UKRI)under the UK Government’s Horizon Europe funding guarantee(grant no.10091247)to T.H.W.+1 种基金arising from the above mentioned EIC Pathfinder grant.The TUM International Graduate School of Science and Engineering(IGSSE)is kindly acknowledged for financial support(International Project Team:Supramolecular Organometallic and Coordination Complexes for Medical Applications,SOCoMED)This research has also received funding from the European Union’s Horizon H2020 Research and Innovation under the Marie Skłodowska-Curie grant agreement no.945416 through the PhD fellowship of IK.
文摘Supramolecular self-assembly is a promising tool to develop multifunctional theranostic agents and has recently entered the field of radiochemistry.In this work,lantern-shaped[Pd_(2)L_(4)]^(4+)metallacages featuring a blood–brain barrier-penetrating peptide were designed for dual-modality imaging.Two silicon-based fluoride acceptors were incorporated in the cage ligand for radiolabeling with fluorine-18,an isotope used in positron emission tomography(PET).Ligands(L1,L2)and the respective homoleptic cages(C1hom[Pd_(2)(L1)_(4)]^(4+),C2hom[Pd_(2)(L2)_(4)]^(4+))were fully characterized by NMR spectroscopy,liquid chromatography and high-resolution electrospray mass spectrometry(HR-ESI-MS).Cage stability was assessed in different solvents and concentrations by HPLC.^(18)F-labelled cages were obtained by radiolabeling the ligands preassembly under mild conditions within four hours via[19F]-to-[^(18)F]isotopic exchange.The high lipophilicity of the ligands was also assessed in vitro(log DpH_(7.4))and in ovo,using the chick chorioallantoic membrane(CAM)model.Furthermore,formation of host–vip complexes between the metallacages and perrhenate(ReO_(4)^(-)),the‘cold’surrogate of radioactive^(99m)TcO_(4)-(used for single photon computed tomography,SPECT),could be detected by mass spectrometry,although the adduct did not sustain chromatographic separation.To improve stability of the supramolecular system,heteroleptic cages of general formula[Pd_(2)(L)m(L0)_(n)]^(4+)(m=1,2,n=4-m)were synthesized by statistical self-assembly and separated by liquid chromatography in good yield.Overall,this study demonstrates the feasible adaptation of supramolecular principles to achieve innovative theranostic agents.
