Porphyrin-based iron-MOF nanoprobe for photoacoustic sensing in a Cu 2+ -Aβ-associated oxidative microenvironment model

The Cu[Formula: see text]-A[Formula: see text] interaction is closely linked to the metal-ion imbalance, peptide aggregation and oxidative stress of Alzheimer’s disease-related microenvironments. Here we report a porphyrin-based iron metal-organic framework (Fe-MOF) nanoprobe for photoacoustic (PA) sensing of a Cu[Formula: see text]-A[Formula: see text]-associated oxidative microenvironment model in vitro. The probe was assembled by solvothermal coordination of the porphyrinic ligand tetrakis(4-carboxyphenyl)porphyrin (TCPP) with Fe nodes, and multiple characterizations confirmed its formation, stable near-infrared absorption and a concentration-dependent PA output. Within the model, the PA response of the Cu[Formula: see text]-A[Formula: see text] group clearly exceeded that of Cu[Formula: see text] or A[Formula: see text] alone and was weakened by N-acetyl-L-cysteine (NAC) or glutathione (GSH). Post-treatment analysis showed that Cu[Formula: see text]-A[Formula: see text] increased the hydrodynamic size and polydispersity index (PDI), lowered the absolute Zeta potential, strengthened near-infrared absorption and raised the Fe[Formula: see text]/Fe[Formula: see text] ratio. 2[Formula: see text],7[Formula: see text]-dichlorodihydrofluorescein diacetate (DCFH-DA) assays revealed elevated reactive oxygen species (ROS); however, the H 2 O 2 group gave high ROS, but only weak PA activation, indicating that increased ROS alone cannot explain the response. In SH-SY5Y cells, the Fe-MOF retained basic cytocompatibility and produced a distinguishable PA response. Overall, this proof-of-concept porphyrin-based Fe-MOF platform shows a PA response that likely arises from the combined contributions of Cu[Formula: see text]-A[Formula: see text]-induced colloidal state, near-infrared absorption and Fe valence modulation.