Luminescent Cyclometalated Iridium(III) Polypyridine Complexes Modified with a Dendritic Guanidinium Moiety as Molecular Glues for Combined Chemo-Photodynamic Therapy.

We report herein three cyclometalated iridium(III) polypyridine complexes appended with a dendritic guanidinium unit Ir(N^C)(bpy-Gu) (bpy-Gu = 4-(-(3,4,5-tris(2-(2-(2-(4-((3,4,5-tris(2-(2-(2-guanidinoethoxy)ethoxy)ethoxy)benz-amido)methyl)-1-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)phenylcarbonyl)aminomethyl)-4'-methyl-2,2'-bipyridine; HN^C = 2-phenylpyridine (Hppy) (), 2-phenylquinoline (Hpq) (), and 2-(1-naphthyl)benzothiazole (Hbsn) ()) as molecular glues. Their guanidinium-free counterparts Ir(N^C)(bpy-C4) (bpy-C4 = 4-(-(-propylcarbonyl)aminomethyl)-4'-methyl-2,2'-bipyridine; HN^C = Hppy (), Hpq (), and Hbsn ()) were also isolated. Irradiation of the complexes led to intense greenish-yellow to red emission. Additionally, the cellular uptake and (photo)cytotoxic effects of the complexes were investigated. Protein-binding studies showed that the decacationic complexes - exhibited high binding affinity toward bovine serum albumin (BSA). Complex was utilized to modify doxorubicin (DOX)-loaded, glutathione (GSH)-responsive BSA nanoparticles (DOX/BNPs), affording Ir-DOX/BNPs. Notably, functionalization of DOX/BNPs with the complex reversed the surface charge from negative to positive. The size of Ir-DOX/BNPs decreased significantly upon incubation with GSH as a result of efficient DOX release. The positively charged Ir-DOX/BNPs showed efficient cellular uptake in HeLa cells, which proved to be crucial for their effectiveness in combined chemo-photodynamic therapy. These results showed that iridium(III)-based molecular glues can be employed for drug delivery and combined chemo-photodynamic therapy.