Porphyrin MOF nanosheets loaded with scorpion venom peptide for synergistic chemo-photodynamic cancer therapy.

Authors

Eman Serag, Esmail M El-Fakharany, Mohamed A Abdel-Rahman, Abeer Ansary, Yousra A El-Maradny, Noran M Tawfik, Youyong Yuan, Mohamed E El-Khouly

Published in

International journal of biological macromolecules. Pages 154419. Sep 15, 2026. Epub Sep 15, 2026.

Abstract

Conventional cancer treatments often fall short, making multimodal therapies essential. This study introduces a novel hybrid nanoplatform, TCPP-MOF-NS@Smp24, created by immobilizing the scorpion venom peptide Smp24 within porphyrin metal-organic framework nanosheets to combine chemotherapy and photodynamic therapy (PDT). The resulting conjugate showed excellent physicochemical stability, strong photosensitizing properties, and high biocompatibility, with hemolysis indices below 2.5% ensuring safety for systemic use. We evaluated the cytotoxicity of TCPP-MOF-NS@Smp24 against HepG2 (liver), MDA-MB-231 (breast), and HCT-116 (colon) cancer cells, as well as normal human skin fibroblasts (HSF), under dark and light-irradiated conditions. Upon photo-irradiation, the nanoplatform demonstrated highly selective cytotoxicity against all cancer lines, outperforming the standard drug 5-fluorouracil (5-FU) while sparing normal cells. It was most effective against HCT-116 colon cancer cells, achieving an IC₅₀ value of 4.43±0.93μg/mL. Flow cytometry revealed that combining Smp24 with light-activated reactive oxygen species caused mitochondrial dysfunction and membrane portion, triggering apoptosis. Furthermore, the nanoplatform favorably modulated the inflammatory microenvironment; in LPS-stimulated cells, it markedly reduced pro-inflammatory cytokines (TNF-α, IL-6) and IL-13, while upregulating caspase-3 activity to drive programmed cell death in cancer cells. Overall, these findings demonstrate that TCPP-MOF-NS@Smp24 is a potent, multifunctional therapeutic system that effectively combines peptide-driven membrane disruption with PDT to deliver highly selective and efficient cancer therapy.

PMID:
42744266
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

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