Hafnium-Based Metal–Organic Framework Nanosystems Entrapping Squaraines for Efficient NIR-Responsive Photodynamic Therapy

Abstract

In this study, we present for the first time the incorporation of two distinct nonsymmetrical squaraines (SQ) into hierarchically porous Hafnium-based UiO-66 Metal–Organic Frameworks (MOFs), each functionalized with various moieties, for application as photosensitizers in photodynamic therapy. SQs are meticulously designed to feature COOH moieties for interaction with the MOF’s metallic cluster and bromine atoms to enhance intersystem crossing and reactive oxygen species (ROS) production. The distinct central functionalizations, one with squaric acid and the other with a dicyanovinyl-substituted squaric acid derivative, result in unique geometric conformations. The latter, as well as the molecular size and density, have been analyzed by computational methods, facilitating the optimal design of MOF cavities for SQ accommodation. Our synthetic methodology involves the production of hierarchically porous Hf-MOFs that integrate both micro- and mesopores. The resultant SQ@MOF systems preserve photosensitizing properties, enhancing solubility and stability without compromising ROS generation or MOF structural integrity. As proof of concept, in vitro evaluations against PANC-1 cells were evaluated, demonstrating the cytocompatibility of SQ@MOFs in the dark up to concentrations of 200 μg mL^–1. Photoactivity is assessed using a statistical multivariate design, enabling identification of the SQ@MOF system with the highest phototoxicity and determination of the variables that significantly influence phototoxicity.