Immobilization of a Carboxylated Iridium(III) Complex on NH2-UiO-66: A Robust MOF-Based Photosensitizer for Photodynamic Therapy

Abstract Photodynamic therapy (PDT) represents a promising noninvasive approach for cancer treatment; however, its therapeutic efficacy is often constrained by hypoxia within the tumor microenvironment, particularly in the highly oxygen-dependent Type II PDT system. In this study, a nanocomposite photosensitizer IrbpyCONH@UiO-66 was developed by conjugating an iridium(III) complex (IrbpyCOOH) with an amino-functionalized zirconium-based metal–organic framework NH2-UiO-66 via an amidation reaction. The material was thoroughly characterized using TEM, SEM, IR, XPS, and elemental mapping, as well as absorption and emission spectroscopy. The nanocomposite IrbpyCONH@UiO-66 retained the photosensitizing properties of IrbpyCOOH as a photosensitizer. Using DPBF and DHR 123 as probes for 1O2 and O2•–, respectively, both IrbpyCOOH and IrbpyCONH@UiO-66 were confirmed as dual Type I/II photosensitizers, generating both 1O2 and O2•– under 420/520 nm light, while the MOF NH2-UiO-66 did not produce ROS under 520 nm. In vitro assays conducted on HeLa, A549, and MKN45 cells demonstrated that the nanocomposite not only showed improved biocompatibility but also enhanced intracellular ROS generation, leading to superior phototoxicity. In vivo experiments further revealed that IrbpyCONH@UiO-66 effectively suppressed MKN45 tumor growth without causing notable tissue damage. These findings highlight that nanocomposite formation significantly enhances PDT efficiency against cancer cells.