A Luminescent Poly(amidoamine)-Iridium Complex as a New Singlet-Oxygen Sensitizer for Photodynamic Therapy

A polymer complex (1(P)) was synthesized by binding bis(cyclometalated) Ir(ppy)(2)(+) fragments (ppy = 2-phenylpyridyl) to phenanthroline (phen) pendants of a poly(amidoamine) copolymer (PhenISA, in which the phen pendants involved similar to 6% of the repeating units). The corresponding molecular complex [Ir(ppy)(2)(bap)](+) (1(M), bap = 4-(butyl-4-amino)-1,10-phenanthroline) was also prepared for comparison. In water solution 1(P) gives nanoaggregates with a hydrodynamic diameter of 30 nm in which the lipophilic metal centers are presumed to be segregated within polymer tasks to reduce their interaction with water. Such confinement, combined with the dilution of triplet emitters along the polymer chains, led to 1(P) having a photoluminescence quantum yield greater than that of 1(M) (0.061 vs 0.034, respectively, in an aerated water solution) with a longer lifetime of the (MLCT)-M-3 excited states and a blue-shifted emission (595 nm vs 604 nm, respectively). NMR data supported segregation of the metal centers. Photoreaction of O-2 with 1,5-dihydroxynaphthalene showed that 1(P) is able to sensitize O-1(2) generation but with half the quantum yield of 1(M). Cellular uptake experiments showed that both 1(M) and 1(P) are efficient cell staining agents endowed with two-photon excitation (TPE) imaging capability. TPE microscopy at 840 nm indicated that both complexes penetrate the cellular membrane of HeLa cells, localizing in the perinuclear region. Cellular photodynamic therapy tests showed that both 1(M) and 1(P) are able to induce cell apoptosis upon exposure to Xe lamp irradiation. The fraction of apoptotic cells for 1(M) was higher than that for 1(P) (74 and 38%, respectively) 6 h after being irradiated for 5 min, but cells incubated with 1(P) showed much lower levels of necrosis as well as lower toxicity in the absence of irradiation. More generally, the results indicate that cell damage induced by 1(M) was avoided by binding the iridium sensitizers to the poly(amidoamine).