Encapsulation of IR783 in UiO-66 MOFs for Improved Photodynamic Efficacy Against Breast Cancer Cells

Abstract

Breast cancer remains the most prevalent malignancy among women worldwide, underscoring the need for innovative therapeutic strategies beyond conventional modalities. Photodynamic therapy (PDT) offers a non-invasive approach that leverages light-activated photosensitizers to induce reactive oxygen species (ROS)-mediated tumor cell death. IR783, a near-infrared fluorescent (NIRF) heptamethine cyanine dye, has shown promise as a theranostic agent in cancer therapy due to its tumor-selective uptake and pro-apoptotic effects. However, its clinical potential is hindered by poor stability, rapid dissociation in polar environments, low quantum yield, and suboptimal tumor accumulation. In this study, we developed a multifunctional nanoplatform by encapsulating IR783 into UiO-66, a zirconium-based metal-organic framework (MOF), to enhance the delivery and photodynamic performance of the dye (IR783@UiO-66). The system was structurally characterized, and its biocompatibility and drug release profiles were evaluated. In vitro experiments were conducted to assess the cytotoxic and phototoxic effects of IR783, UiO-66, and IR783@UiO-66 on breast cancer cell lines (MCF-7, MDA-MB-231) and normal breast epithelial cells (MCF-10A), under LED irradiation at varying light intensities (18-144 J/cm2) and exposure durations (7.5-60 min). The results demonstrated that IR783@UiO-66 significantly reduced cancer cell viability in a dose-and light-dependent manner while sparing normal cells. Free IR783 showed slightly higher phototoxicity, attributed to differences in release kinetics and loading efficiency. UiO-66 alone exhibited negligible cytotoxicity under irradiation, confirming its safety profile. This study highlights the potential of UiO-66 as a promising nanocarrier for enhancing IR783-mediated PDT, offering a synergistic strategy for targeted and efficient breast cancer therapy.