Photodynamic therapy (PDT) is an emerging strategy for cancer treatment and represents a promising approach for melanoma, one of the most aggressive and therapy-resistant forms of skin cancer. In this study, meso-tetra(4-pyridyl)porphyrin complexes coordinated with palladium(II)/diphosphine ligands (Porf@dppe, Porf@dppp, Porf@dppb, and Porf@dppf; dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, and dppf = 1,1′-bis(diphenylphosphino)ferrocene), previously shown to display favorable lipophilicity and efficient singlet oxygen production, were evaluated against human (A375) and murine (B16-F10) melanoma cells, as well as non-cancerous keratinocytes (HaCaT). Cytotoxicity measured after a 90 min incubation period yielded dark IC 50 values between 0.6 and 8.6 μM, whereas light irradiation (λ = 415 nm, 1.8 J cm -2 , 36 mW cm -2 ) resulted in markedly lower IC 50 values in the nanomolar range (2–27 nM). Irradiation increased intracellular ROS levels, induced morphological alterations in A375 cells, inhibited long-term proliferation, and reduced cell migration, particularly for Porf@dppb and Porf@dppf. The highest cytotoxicity was observed for Porf@dppf, likely due to the redox-active ferrocene unit promoting Fenton-type reactions and enhanced hydroxyl radical formation. Electron paramagnetic resonance (EPR) spin-trapping experiments confirmed light-induced generation of singlet oxygen, hydroxyl radicals, and superoxide anion, with significantly higher hydroxyl radical production observed for Porf@dppf. The photodynamic activity of these complexes is attributed to efficient ROS production involving simultaneous contributions from both Type I and Type II mechanisms. Moderate binding to bovine serum albumin suggests possible albumin-mediated plasma transport. Overall, palladium(II)/diphosphine porphyrin complexes emerge as promising photosensitizers for melanoma photodynamic therapy. • Under 415 nm irradiation, IC 50 values decrease markedly compared to dark conditions • ROS overproduction induces mitochondrial and lysosomal damage, apoptosis, and DNA cleavage • Static BSA quenching (K b ≈ 10 5 L·mol -1 ) indicates reversible plasma transport potential
Moraes et al. (Sun,) studied this question.