Rational design of iridium-porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents.

Near-infrared (NIR) emitters are important probes for biomedical applications. Nanoparticles (NPs) incorporating mono- and tetranuclear iridium(iii) complexes attached to a porphyrin core have been synthesized. They possess deep-red absorbance, long-wavelength excitation (635 nm) and NIR emission (720 nm). TD-DFT calculations demonstrate that the iridium-porphyrin conjugates herein combine the respective advantages of small organic molecules and transition metal complexes as photosensitizers (PSs): (i) the conjugates retain the long-wavelength excitation and NIR emission of porphyrin itself; (ii) the conjugates possess highly effective intersystem crossing (ISC) to obtain a considerably more long-lived triplet photoexcited state. These photoexcited states do not have the usual radiative behavior of phosphorescent Ir(iii) complexes, and they play a very important role in promoting the singlet oxygen (1O2) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high 1O2 generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC50) (0.057 µM), excellent photothermal imaging and synergistic PDT and PTT under 635 nm laser irradiation. To our knowledge this is the first example of iridium-porphyrin conjugates as PSs for photothermal imaging-guided synergistic PDT and PTT treatment in vivo.

Near-infrared-emitting AIE multinuclear cationic Ir(III) complex-assembled nanoparticles for photodynamic therapy.

Near-infrared (NIR) emission and impressive singlet oxygen (1O2) generation ability are highly desirable but remain difficult to realize as aggregation-induced emission (AIE) photosensitizers (PSs). Herein, mono- and tri-nuclear NIR AIE cationic Ir(iii) complexes and their corresponding self-assembled nanoparticles (NPs) without any surfactants or adjuvants were designed and synthesized by integrating rigid 1,3,5-triphenyl benzene as an extended π-conjugation bridge. The pure NPs exhibit multiple merits of stronger NIR emission, higher 1O2 production capacity, better water solubility and negligible dark toxicity compared with the Ir(iii) complexes. Notably, the AIE PS3 NPs possess bright NIR emission at 730 nm, suitable spherical sizes below 100 nm, favorable cellular uptake and superior phototoxicity (IC50 = 1.4 × 10-6 M). These are the first pure NIR-emitting multinuclear Ir(iii) complex NPs obtained by self-assembly that exhibit excellent cell imaging and photodynamic therapy (PDT) performance.

Water-soluble cyclometalated Ir(III) complexes as carrier-free and pure nanoparticle photosensitizers for photodynamic therapy and cell imaging.

Herein, we provide a new and facile strategy to successfully overcome the inherent aggregation-caused quenching effect and hydrophobicity that exist in traditional PSs by the introduction of sodium salts. The obtained water-soluble Ir(iii) complexes as carrier-free and pure nanoparticle photosensitizers exhibit excellent performance in photodynamic therapy and cell imaging.