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PT@MOF With Autophagy Inhibitory Effect Is Used To Improve The Photodynamic Efficacy Of Tumor

Posted on:2023-01-07Degree:MasterType:Thesis
Country:ChinaCandidate:X Y HanFull Text:PDF
GTID:2544306794498764Subject:Bio-engineering
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According to statistics,nearly 10 million people die of cancer every year,which is the most serious human health problem.As a new type of therapy,photodynamic therapy is attracting more and more attention and research.Compared with traditional treatment methods,it is controllable,minimally invasive,and has fewer side effects.PDT is mainly composed of three parts: specific light,oxygen and photosensitizer.The photosensitizer will catalyze oxygen to generate toxic singlet oxygen after being irradiated by specific light,thereby killing tumors.However,porphyrin photosensitizers have poor water solubility,and the hypoxic environment and autophagy behavior of tumors severely limit the efficiency of PDT and reduce the therapeutic effect on tumors.In this paper,in order to enhance the water solubility of porphyrin photosensitizers,porphyrins were linked to inorganic metal zirconium ions by chemical synthesis to synthesize metal-organic framework(MOF)PCN-224,and platinum nanoparticles were modified by in situ reduction method.On the surface of MOF,this particle has catalase activity,in cancer cells,thereby increasing the efficacy of PDT.Finally,HCQ,an autophagy inhibitor,was loaded by the pore-channel effect of MOF,which could be released in the ATP-rich tumor environment and cut off the self-protection mechanism generated by severe injury caused by photodynamic therapy,thereby enhancing the damage to tumor cells.Scanning electron microscopy,UV spectroscopy and other methods prove that we have successfully synthesized Pt@PCN-224+HCQ nanomaterials,which can reach 80% HCQ release rate within 4 h in the presence of ATP.At the same time,the cell-level experiments show that Pt@PCN-224+HCQ has high photodynamic efficacy,catalase activity and autophagy inhibition,which can make 4T1 mouse breast cancer cells achieve 52.02% apoptosis Rate.Experiments show that the modification of platinum nanoparticles can improve the efficacy of PDT and synergize with autophagy inhibition.
Keywords/Search Tags:Metal organic frameworks, photodynamic therapy, nanocatalysis, autophagy inhibition
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