Porphyrin-based zinc metal–organic framework loaded with gallic acid as a novel nanoplatform exhibiting H2O2-activated reactive oxygen species generation and cytotoxicity in breast cancer cells

Abstract

A zinc-based metal–organic framework (MOF) engineered from tetrakis(4-carboxyphenyl) porphyrin (TCPP) as an organic linker and functionalized with gallic acid (GA) as an active therapeutic agent demonstrates remarkable potential for cancer treatment. The resulting Zn-TCPP@GA hybrid framework exhibits a high specific surface area, extensive π–π conjugation, and superior catalytic performance, collectively facilitating efficient reactive oxygen species (ROS) generation-an essential mechanism underlying chemodynamic therapy (CDT). Incorporation of GA significantly enhances the redox activity and biocompatibility of the framework. GA actively participates in modulating the tumor environment by depleting intracellular glutathione (GSH), thereby impairing the antioxidant defense machinery of cancer cells and amplifying ROS-mediated oxidative stress. Comprehensive physicochemical characterization confirmed that Zn-TCPP@GA exhibits an intrinsic peroxidase-mimetic and ROS generation mechanism via catalyzing the decomposition of hydrogen peroxide (H₂O₂) into highly reactive hydroxyl radicals (˙OH). This catalytic conversion markedly augments intracellular ROS accumulation, resulting in pronounced oxidative damage and selective cytotoxicity toward malignant cells while sparing normal tissues. In vitro cytotoxicity evaluation revealed that Zn-TCPP@GA at a concentration of 75.04 µg mL⁻¹ induced approximately a 50% reduction in MCF-7 breast cancer cell viability, with negligible impact on normal cell lines. Collectively, these findings substantiate Zn-TCPP@GA as a potent CDT nanotherapeutic platform, capable of tumor-selective ROS amplification through peroxidase-like catalysis and chemodynamic biochemical modulation mediated by gallic acid.