摘要
Photodynamic therapy (PDT) is an attractive clinical technique for cancer treatment. However, the poor solubility and weak cellular internalization of the molecule-photosensitizers, as well as the exceedingly short lifetime and limited diffusion distance of the generated reactive oxygen species (ROS) in cytoplasm directly restricted the therapeutic efficiency of conventional PDT. In this study, we proposed a facile strategy for improving PDT of cancer based on a mitochondria-targeted nanophotosensitizer. The molecule-photosensitizer chlorin e6 was covalently attached on the internal and external surfaces of the mesoporous silica nanoparticles. Then, the triphenylphosphonium was anchored on the nanoparticles for selectively targeting mitochondria. When irradiated with laser, the nanophotosensitizer can generate a large amount of ROS in mitochondria, thus causing the mitochondrial dysfunction and irreversible cell apoptosis. In vitro and in vivo studies demonstrated that the nanophotosensitizer could boost the treatment efficiency against cancer cells and xenograft tumor models.
Photodynamic therapy(PDT)is an attractive clinical technique for cancer treatment.However,the poor solubility and weak cellular internalization of the molecule-photosensitizers,as well as the exceedingly sho rt lifetime and limited diffusion distance of the generated reactive oxygen species(ROS)in cytoplasm directly restricted the therapeutic efficiency of conventional PDT.In this study,we proposed a facile strategy for improving PDT of cancer based on a mitochondria-targeted nanophoto sensitizer.The molecule-photo sensitizer chlorin e6 was covalently attached on the internal and exte rnal surfaces of the mesoporous silica nanoparticles.Then,the triphenylphosphonium was ancho red on the nanopa rticles fo r selectively targeting mitochondria.When irradiated with laser,the nanophotosensitizer can generate a large amount of ROS in mitochondria,thus causing the mitochondrial dysfunction and irreversible cell apoptosis.In vitro and in vivo studies demonstrated that the nanophotosensitizer could boost the treatment efficiency against cancer cells and xenograft tumor models.
基金
supported by the National Natural Science Foundation of China(Nos. 21535004, 91753111, 21874086, 21775094, 21505087, 21390411)
the Key Research and Development Program of Shandong Province(No. 2018YFJH0502)
