# 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

**Authors:** May R. Ibrahim, Shaikha Alneyadi, Hesham El-Maghraby, Stefan Wuttke, Yaser Greish

PMC · DOI: 10.1039/d5ra09585a · RSC Advances · 2026-03-02

## TL;DR

A new zinc-based MOF loaded with gallic acid generates reactive oxygen species to selectively kill breast cancer cells.

## Contribution

A novel nanoplatform combining a porphyrin-based MOF and gallic acid for chemodynamic therapy in breast cancer.

## Key findings

- Zn-TCPP@GA efficiently generates ROS via peroxidase-like activity, enhancing oxidative stress in cancer cells.
- GA depletes glutathione, impairing cancer cell antioxidant defenses and amplifying ROS effects.
- Zn-TCPP@GA showed 50% reduction in MCF-7 cell viability at 75.04 µg mL−1 with minimal impact on normal 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.

A novel zinc-based 2-dimensional porphyrin metal–organic framework (MOF), and further functionalized with gallic acid (GA) as an active therapeutic agent demonstrates remarkable potential for anticancer applications.

## Linked entities

- **Chemicals:** gallic acid (PubChem CID 370), hydrogen peroxide (PubChem CID 784), glutathione (PubChem CID 124886)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Diseases:** Necrosis (MESH:D009336), MCF-7 (MESH:C537955), breast cancer (MESH:D001943), weight loss (MESH:D015431), Cytotoxicity (MESH:D064420), CDT (MESH:D016609), colon cancer (MESH:D015179), hypoxia (MESH:D000860), Cancer (MESH:D009369), MOF (MESH:D013651)
- **Chemicals:** ROS (MESH:D017382), Mn (MESH:D008345), EE (MESH:D004997), hydrogen (MESH:D006859), Zinc nitrate hexahydrate (MESH:C042103), Talaporfin (MESH:C053434), PBS (MESH:D007854), DMF (MESH:D004126), OH (MESH:C031356), pyrrole (MESH:D011758), H O (MESH:D006695), lipids (MESH:D008055), CO2 (MESH:D002245), GSH (MESH:D005978), Terephthalic acid (MESH:C011363), bicarbonate (MESH:D001639), MTT (MESH:C070243), mercury (MESH:D008628), proton (MESH:D011522), Foscan (MESH:C072269), H2S (MESH:D006862), 2-hydroxyterephthalic acid (MESH:C406866), Porphyrin (MESH:D011166), cisplatin (MESH:D002945), NaHCO3 (MESH:D017693), H2O2 (MESH:D006861), propidium iodide (MESH:D011419), Cu2+ (-), hydroxyl (MESH:D017665), ethanol (MESH:D000431), Cu (MESH:D003300), PVP (MESH:D011205), propionic acid (MESH:C029658), Fe (MESH:D007501), MB (MESH:D008751), CuS (MESH:C017846), water (MESH:D014867), benzene (MESH:D001554), C (MESH:D002244), N (MESH:D009584), carboxylic acid (MESH:D002264), MOF (MESH:D000073396), Zinc (MESH:D015032), O (MESH:D010100), perylene (MESH:D010569), GA (MESH:D005707), methanol (MESH:D000432), platinum (MESH:D010984), metal (MESH:D008670)
- **Cell lines:** OEC — Homo sapiens (Human), Gingival squamous cell carcinoma, Cancer cell line (CVCL_6782), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

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## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12951844/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12951844/full.md

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Source: https://tomesphere.com/paper/PMC12951844