Covalently Surface-Functionalized Porphyrins on Silica Nanoparticles for Efficient Photodynamic Therapy

Silica nanoparticles (SiNPs) are widely explored as biocompatible platforms for the delivery of photosensitizers in photodynamic therapy (PDT). In this work, porphyrins bearing amine (PNH₂) or carboxyl (PCOOH) groups were covalently conjugated onto functionalized SiNP surfaces via carbodiimide-mediated amide coupling, yielding the silica-porphyrin nanohybrids H-PNH₂ and H-PCOOH. Successful surface functionalization was confirmed by Fourier-transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. Photophysical studies demonstrated that both nanohybrids retained efficient singlet oxygen (¹O₂) generation. In vitro biological assays revealed a strong dependence of photodynamic activity on the nature of the conjugated porphyrin, with H-PCOOH exhibiting markedly enhanced photocytotoxicity with respect to the free porphyrins, while H-PNH₂ showed an attenuated light-dose response. Notably, H-PCOOH induced pronounced cell death at low light doses (1 J/cm²), with a half-maximal inhibitory concentration (IC₅₀) below 0.3 µM. These findings highlight the potential of silica-porphyrin nanohybrids as efficient photosensitizers for PDT applications.