Singlet Oxygen Generation in Ferriporphyrin-Polymer Dots Catalyzed Chemiluminescence System for Cancer Therapy

Chemiluminescence (CL) systems have been used as excitation sources through chemiluminescence resonance energy transfer (CRET) between CL substrates and photosensitizers for photodynamic therapy (PDT). However, it is still a tremendous challenge to construct a highly effective CL system that has a strong emission intensity and long duration time for PDT. Here, we constructed a Fe(III) deuteroporphyrin IX chloride-polymer dots (FeDP-Pdots) catalyzed CL system for cancer therapy, where the CL system was used as the generation of singlet oxygen for inhibiting and killing tumor cells with the use of FeDP-Pdots as both the catalysts and the photosensitizers. We prepared metalloporphyrin-polymer dots (M-Pdots) by nanoprecipitation and systematically investigated the relationship between the catalytic CL activities of M-Pdots and the structures of metalloporphyrins. It is found that FeDP-Pdots have the highest catalytic activity among 11 M-Pdots. Their CL intensity is almost 200-fold higher than the hemin-Pdots catalyzed system. The strong catalytic activity of FeDP is derived from its center ion Fe(III), carboxyl groups, conjugated system, and smaller steric hindrance. Importantly, our results demonstrated that the higher the chemiluminescence intensity is, the more reactive oxygen species are produced during the Pdots catalyzed CL reaction. The FeDP-Pdots catalyzed luminol analogue L012-H₂O₂ CL system was used successfully for in vitro and in vivo cancer therapy. Our proposed method is characterized by the mass production of singlet oxygen through CRET and no requirement of light source. It is simple, selective, and effective, which develops a strong emission intensity and long-duration CL system for PDT and can be applied for the therapy of deep cancer tissues.