Enhancing Photodynamic Therapy Efficacy of Upconversion-Based Nanoparticles Conjugated with a Long-Lived Triplet Excited State Iridium(III)-Naphthalimide Complex: Toward Highly Enhanced Hypoxia-Inducible Factor-1

Metal-based photosensitizers are of great interest in photodynamic therapy (PDT) due to their tunable photo-physicochemical characteristics and structure flexibility. Herein, an iridium-based photosensitizer (1) with a long-lived intraligand (3IL) excited state has been designed and synthesized, which shows significantly enhanced singlet oxygen (1O2) generation efficiency (~45 folds) relative to that of the model iridium(III) complex (2) under 460 nm irradiation. In order to achieve deep tissue penetration, complex 1 was further covalently bonded to the upconversion nanoparticles (UCNPs). Besides, 1-benzyl-3-(5’-hydroxymethyl-2’-furyl)indazole (YC-1), an effective HIF-1α inhibitor, was physically adsorbed on the surface of UCNPs via hydrophobic interactions. Once upon near-infrared (NIR) irradiation, iridium complex 1-mediated toxic 1O2 was generated for PDT, whose efficient conversion of oxygen to 1O2 during the PDT would exacerbate the hypoxic condition of tumor tissue and result in the upregulation of ...