Active targeted photodynamic therapeutic effect of silver-based nanohybrids on melanoma cancer cells

Malignant melanoma is aggressive cancer that metastasizes along with the heterogeneity at the molecular and cellular levels, thereby reducing overall therapeutic efficacy. In the present research, the concept of photodynamic therapy (PDT) was investigated on silver-based nanohybrids for the treatment of A375 melanoma cancer cells. Hence, two different nanoparticles (NPs) namely Ag-PEG NPs and core/shell Ag@mSiO₂ NPs were fabricated and conjugated to zinc phthalocyanine tetrasulfonate (ZnPcS₄) photosensitizer (PS). Folic acid (FA) as a targeting moiety was also decorated onto the surface of nanohybrids to selectively target the folate receptors that are overexpressed on the A375 cells. Ultimately, the PDT efficacy of both ZnPcS₄/Ag-PEG-FA and ZnPcS₄/Ag@mSiO₂-FA nanohybrids were compared via ATP viability, flow cytometry, and reactive oxygen species (ROS) assays. The obtained near-spherical shaped nanohybrids had zeta potential of -4.03 ± 0.3 mV for ZnPcS₄/Ag-PEG-FA, and -14.4 ± 0.6 mV for the ZnPcS₄/Ag@mSiO₂-FA. A significant PDT effect was observed for the cells exposed to 674 nm laser irradiation after incubation with ZnPcS₄/Ag@mSiO₂-FA with ∼92%* ± 1.1 cell death compared to ∼70%* ± 2.9 cell death for ZnPcS₄/Ag-PEG-FA nanohybrids owing to the higher generation of ROS for the former nanohybrids. The majority of the cell death was induced via apoptosis rather than necrosis as the nanohybrids successfully localized in mitochondria. The overall finding of this study concluded that an active targeting strategy significantly enhanced the cellular uptake of the nanohybrids compared to passive targeting. Moreover, strong surface plasmon-PS resonance coupling in ZnPcS₄/Ag@mSiO₂-FA nanohybrids enhanced singlet oxygen generation in comparison to the PS alone or ZnPcS₄/Ag-PEG-FA nanohybrids.