Stimuli-responsive protoporphyrin IX silica-based nanoparticles for photodynamic therapy in vitro

Nanoparticle-based delivery systems have been explored recently as efficient vehicles to transport photosensitizers for photodynamic therapy (PDT). In this study; we report the synthesis, characterization and in vitro application of a stimuli-responsive silica nanoparticle platform chemically functionalized with protoporphyrin IX (RR-PpIX-SiNPs). PpIX photosensitizers have been attached to the surface of SiNPs through a redox-responsive linker. PpIX molecules can be selectively released from the RR-PpIX-SiNP platform in their monomeric form in the presence of the highly reducing environment found in cancer cells. The structural, photophysical and photochemical properties of RR-PpIX-SiNPs were characterized and compared with a control sample (PpIX-SiNPs), which does not contained a redox-responsive linker. Cell viability measurements demonstrated that RR-PpIX-SiNPs were more phototoxic than PpIX-SiNPs. Confocal microscopy shows that RR-PpIX-SiNPs are mainly localized in lysosomes. Finally, the redox-responsive release of PpIX molecules was demonstrated in solution and in vitro using UV-vis spectrometry and confocal microscopy, respectively. We envision that further modification of this platform can render colloidal stability and target-specific properties by grafting polymeric chains and small molecules or biomolecules.