Persistent luminescent nanoparticles as energy mediators for enhanced photodynamic therapy with fractionated irradiation

Abstract

The excitation wavelengths of most porphyrin-based photosensitizers are in the ultraviolet (UV) spectrum. Prolonged irradiation of living cells and tissues with UV light during the clinical application of photodynamic therapy (PDT) may cause DNA damage and cell death. Here, we report a novel persistent-luminescent nanoparticle (PLNP)-based PDT approach that uses the afterglow property of PLNPs to greatly reduce the dose of UV light while maintaining the desired cancer suppression effect. Multifunctional PLNPs coated with mesoporous silica layers and subsequently conjugated to a photosensitizer were evaluated. These nanoconjugates showed high colloidal stability and biocompatibility. Furthermore, they generated a moderate amount of ¹O₂ through efficient energy transfer from the nanoparticle to the photosensitizer, which can efficiently damage cancer cells. In addition to their UV-excited luminescence, PLNPs also exhibited a long-lasting luminescence afterglow. Thus, PLNPs can serve as a persistent light source for PDT activation after excitation by an external light source is stopped. When fractionated light was used for excitation instead of continuous light at equivalent irradiation doses, confocal microscopy revealed that the photosensitizer-conjugated PLNPs showed a significantly enhanced cancer cell killing ability. Moreover, quantitative flow cytometry showed that fractionated light irradiation (60 s/100 s on/off cycle) produced up to ten times more cancer cell apoptosis/necrosis than the same dose of continuous light irradiation did. These results indicate that photosensitizer-conjugated PLNPs combined with fractionated irradiation show good potential for low-dose UV-mediated PDT activation.