Surface-Functionalized Porphyrinic MOF Nanocarrier with Intrinsic Fluorescence for Enhanced DNA Delivery and Combined Phototherapy

Abstract Multifunctional nonviral gene carriers face the challenge of reconciling efficient DNA condensation, fluorescence traceability, controlled intracellular release, and phototherapeutic activity within a single platform. To address this, we constructed a surface-functionalized porphyrinic metal–organic framework nanocarrier, PCN–PFN, by covalently grafting polyethylenimine-derived fluorescent carbon dots (PFN) onto PCN-224. This design creates spatially distributed cationic domains on a rigid porphyrinic scaffold, combining accessible amine groups and intrinsic fluorescence with the structural integrity and light-responsive functions of the MOF framework. PCN–PFN achieved approximately 90% DNA binding efficiency at a carrier/DNA mass ratio of 2:1, protected DNA from DNase I degradation, reduced nonspecific protein adsorption, and exhibited favorable cytocompatibility. The complexes showed acid-accelerated DNA release and enabled label-free visualization of cellular uptake. In 293T cells, PCN–PFN/DNA mediated a transfection efficiency of 81.88%, surpassing that of PFN/DNA. Under 808 nm irradiation, PCN–PFN exhibited a quantifiable photothermal effect with a conversion efficiency of 35.37%; short-term irradiation selectively enhanced transfection in HeLa cells (from 50.03% to 63.56%) but not in 293T cells. Combined 660 and 808 nm irradiation generated both reactive oxygen species and photothermal heating, achieving superior cancer cell elimination over either single-wavelength treatment. Collectively, these findings establish covalent carbon-dot functionalization as a versatile strategy to integrate traceable gene delivery, light-assisted transfection, and combined photodynamic/photothermal therapy within a porphyrinic MOF nanocarrier.