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 (O-1(2)) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high O-1(2) generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC50) (0.057 mu M), 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.