Cancer, also known as malignant tumor, is one of the major diseases that seriously affect the safety of human life. Tens of millions of patients die of cancer every year in the world. At present, the incidence and mortality of cancer are rising continuously, which has become a public health problem that the whole society must attach great importance to. Operation, chemotherapy and radiotherapy are the most widely used tumor treatment methods in clinic. However, these traditional treatment methods have some limitations, such as large trauma, high side effects, easy metastasis and recurrence, which lead to a low five-year survival rate. It is an effective way to achieve early treatment of tumor to find high-efficiency and low toxicity specific tumor drugs and explore new precise treatment methods. Photodynamic therapy (PDT) is a new method of tumor treatment. Compared with the traditional treatment, PDT has the advantages of low toxicity, high selectivity and low invasion. According to the reactive oxygen species (ROS), photodynamic therapy can be divided into type I therapy and type II therapy. Type I pathway mainly generates superoxide radicals, hydroxyl radicals, hydrogen peroxide and other cytotoxic species through electron transfer; type II mechanism mainly generates singlet oxygen through energy transfer, promoting cell necrosis and apoptosis. Among them, type II mechanism is a kind of photodynamic therapy widely studied at present, which mainly depends on the singlet oxygen produced to treat the diseased tissue. However, the type II photodynamic therapy is regulated by the oxygen concentration. When the oxygen concentration is low, it can not produce a lot of singlet oxygen, especially in the tumor. With the rapid consumption of oxygen in the process of type II PDT, tumor hypoxia will occur, which can not achieve the ideal therapeutic effect. Compared with type II PDT, type I PDT is a non oxygen dependent treatment process. Due to disproportionation reaction and Harber Weiss / Fenton reaction, even in the case of severe hypoxia (2% O2), it can effectively generate peroxyanion free radical, hydroxyl free radical and other active species in situ of tumor, effectively killing tumor cells. Therefore, it is very urgent to develop type I photosensitizers which can effectively remove primary tumors.
The research team of Professor Dong Xiaochen and associate professor Shao Jinjin of Nanjing University of technology and Associate Professor Xu Zhigang of Southwest University proposed a new type I photosensitizer design strategy, prepared a kind of AZA BODIPY based nano photosensitizer which can produce superoxide radicals efficiently, and studied its treatment performance of hypoxic tumor. The electronic rich diisopropylamine functional group was used to improve the electron delivery ability (mpeg-ppda) of amphiphilic polymer, and iodine substitution was used to improve the jumping ability of AZA BODIPY photosensitizer. The amphiphilic nano photosensitizer ppiab NPs was prepared by self-assembly. The nano photosensitizer has strong near-infrared absorption performance, and can effectively produce charge separated state under 660 nm laser irradiation, and react with oxygen to produce superoxide radicals with cytotoxicity. Cell and in vivo experiments showed that ppiab NPs could produce superoxide free radicals and kill tumor cells even under the condition of high oxygen deficiency (2% O2), which provided a new idea for the rational design of type I photosensitizers. Relevant work was published on small methods (boosting O2 ● - photogeneration via promoting inter system crossing and electron donating efficiency of AZA BODIPY based nanoplatforms for typoxic Tumor Photodynamic therapy, small methods (DOI: 10.1002 / SMTD. 202000013). Chen Dapeng, a doctoral student of Nanjing University of technology, is the first author of this paper.
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