Redox-sensitive Alginate Prodrug Nanoparticles for Tumor Photodynamic Therapy

Nanoparticles have been extensively explored as an effective means to deliver photosensitizers for photodynamic therapy (PDT) against cancer. In this work, Pheophorbide A (PheoA), a hydrophobic photosensitizer, was conjugated to natural polysaccharide alginate (PheoA-ALG) via a redox-sensitive disulfide linkage. The critical aggregation concentration (CAC) of PheoA-ALG in aqueous solution was 73.51 mu g/mL, detected by pyrene monomer fluorescence probe technology. The resulting amphiphilic PheoA-ALG could form self-assembled nanoparticles (PheoA-ALG NPs) in an aqueous medium as prodrug nanoparticles for tumor photodynamic therapy. The physical and chemical properties of PheoA-ALG NPs were studied. TEM and DLS revealed that PheoA-ALG NPs were monodisperse spherical structures with a hydrodynamic diameter about 198 nm. PheoA release profiles in vitro indicated that PheoA release from PheoA-ALG NPs was redox-sensitive. Whereafter, the cellular uptake and cytotoxicity of PheoA-ALG NPs were investigated in vitro. Cellular uptake results showed that PheoA-ALG NPs were readily taken up by B16 tumor cells and enhanced PheoA uptake was detectable in PheoA-ALG NPs-treated B16 cells in comparison to carrier free drugs. Under light irradiation, PheoA-ALG NPs also elicited intracellular ROS generation, which led to an enhanced toxicity in B16 cells both in vitro and in vivo. The CCK-8 assay showed that PheoA-ALG NPs had good cellular compatibility without cytotoxic in vitro without light irradiation, and PheoA-ALG NPs exhibited light dependent cytotoxic response to B16 cells. After light irradiation, IC50 of PheoA-ALG NPs decreased to 0.16 mu g mL(-1), which was about 0.67-fold lower than those of the free PheoA groups with light irradiation. In vivo anti-tumor efficacy of PheoA-ALG NPs was assessed using B16 tumor-bearing mice. Notably, mice treated with PheoA-ALG NPs under light irradiation displayed the highest inhibition ratio of 72.8%, among those treated with free PheoA (45.8%). These results suggest that PheoA-ALG NPs have good potential for tumor photodynamic therapy.