TPEDCC-PEG-based photodynamic therapy exhibits potent therapeutic efficacy against echinococcosis by inducing oxidative stress and mitochondria-mediated apoptosis

Alveolar echinococcosis (AE) is a fatal zoonosis caused by the larval stage of Echinococcus multilocularis, but there are no fully effective treatments for this disease to date. The aim of this study was to investigate the potential therapeutic implication of photodynamic therapy (PDT) for E. multilocularis. We synthesized a novel nanophotosensitizer, TPEDCC-PEG, with aggregation-induced emission (AIE) properties and investigated its in vitro and in vivo PDT effects against the larval stage of E. multilocularis, as well as the anti-Echinococcus mechanism. TPEDCC-PEG exhibited excellent physicochemical properties and biocompatibility as a nanophotosensitizer. TPEDCC-PEG PDT, the treatment of TPEDCC-PEG with 410 nm laser irradiation, showed significant dose- and time- dependent protoscolicidal effect on in vitro cultured protoscoleces. Meanwhile, the infection experiments in vivo showed that the growth of protoscoleces survived after TPEDCC-PEG PDT was significantly suppressed in vitro, and the weight of metacestodes resulting from such protoscoleces in TPEDCC-PEG PDT mice was significant less than that in controls. Once every 3 days PDT administration (410 nm, 10 min) of TPEDCC-PEG (10 mg/kg) for 9 days in E. multilocularis-infected mice was highly effective in reducing the volume of metacestode cysts, resulting in a significant inhibition in metacestodes growth and severe structural destructions of metacestodes. Furthermore, TPEDCC-PEG PDT significantly increased the production of reactive oxygen species (ROS), inhibited the expression of glutathione in protoscoleces, and was accompanied by the depolarization of mitochondrial membrane potential. Western blot analysis revealed significantly reduced expression of the Bcl-2 protein alongside increased expression of caspase-3, Bax, and cytochrome c (Cyt C) proteins in protoscoleces following TPEDCC-PEG PDT, which hints the induction of apoptosis would associate with oxidative stress and involve the mitochondrial pathway. Taken together, the results suggest that PDT with TPEDCC-PEG, which exerted potent parasiticidal effects against E. multilocularis both in vitro and in vivo, could thus serve as a promising therapeutic option for echinococcosis.