Protoporphyrin IX-loaded solid lipid nanoparticles for dual-wavelength photodynamic therapy of melanoma

Abstract Lipid nanoparticles have emerged as promising nanocarriers for improving the delivery of both hydrophobic and hydrophilic photosensitizers and enhancing therapeutic efficacy in photodynamic therapy (PDT). In this study, a biocompatible PDT agent was developed by encapsulating the hydrophobic photosensitizer protoporphyrin IX (PPIX) into solid lipid nanoparticles (SLN) composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and cholesterol using a thin-film hydration and ultrasonication method. The resulting PPIX-loaded SLN (PPIX@SLN) exhibited a uniform hydrodynamic size of approximately 100 nm, good colloidal stability, and efficient drug encapsulation. Optical characterization confirmed that the photophysical properties of PPIX were well preserved after encapsulation. Under 420 nm LED irradiation, the PPIX@SLN generated singlet oxygen ( 1 O 2 ) with a quantum yield of 6%. In vitro studies under dark condition revealed enhanced cellular uptake and minimal cytotoxicity in contrast to previously reported PPIX-loaded nanostructured lipid carriers (PPIX@NLC). Upon irradiation at 420 nm–630 nm, PPIX@SLN induced strong phototoxicity, as verified by both live/dead staining and cytotoxicity assay. The IC 50 values under 420 nm light were as low as 2.19 μg ml −1 for A2058 cells and 1.58 μg ml −1 for B16F10 cells, while the values under 630 nm light were calculated to be 10.12 μg ml −1 and 9.28 μg ml −1 , respectively, demonstrating potent photodynamic activity across multiple melanoma cell lines. These results highlight the excellent biocompatibility and enhanced PDT performance of PPIX@SLN, suggesting its promising potential as a translatable nanomedicine for broad-spectrum anticancer therapy.