Metal–organic framework MIL-101(Fe) functionalized with folic acid as a multifunctional nanocarrier for targeted chemotherapy–photodynamic therapy

A novel folic acid-conjugated, iron-based MOF (MIL-101(Fe)) loaded with 1,8-acridinediones (DO8) was developed for targeted photodynamic therapy (PDT) of HepG-2 cells. This composite aims to trigger an anticancer response through sequential PDT and chemotherapy. The nanocomposite exhibited high stability in a physiological environment with a pH of 7.4. It was also able to release DO8 continuously in an acidic environment with a pH of 5, which shows that it can adapt to the conditions in the tumor microenvironment. The MIL-101(Fe)MOF-FA@DO8 nanoparticles (NPs) with 30% and 50% DO8 have been studied <i>in vitro</i> under different conditions (light and dark) and have been shown to be compatible with living tissues and specifically target HepG-2 cells. The IC₅₀ values of 50% DO8 and 30% DO8 loaded MOF-FA were found to be 88.67 and 105.9 μg mL^-1 under dark conditions, respectively. Under light conditions, they demonstrated the highest efficacy in inhibiting tumor cell growth. The IC₅₀ values were found to be 8.94 and 11.78 μg mL^-1. Flow cytometry analysis of annexin V/PI-stained apoptotic and necrotic cells in HepG-2 cells treated with the modified MIL-101-FA@50% DO8 NPs at IC₅₀ doses under both dark and light conditions indicates that the primary mechanism of cell death is necrosis, likely due to the enhanced formation of reactive oxygen species (ROS) under light conditions compared to that under dark conditions. This increased reactive oxygen species (ROS) generation leads to extensive membrane rupture, resulting in significant cell damage after treatment with the modified MIL-101-FA@50% DO8 NPs. These findings underscore the potential of this nanocomposite as an effective PDT agent for targeted cancer therapy.