Study On Photodynamic Activity Of A Platinum Phenylenediimine Complex Modified With Triphenylphosphonium

Cancer is a major disease in the world.Although chemotherapy,radiotherapy and other methods are used to treat cancer,the therapeutic effect of cancer is not good,and ground-breaking treatment methods are still needed.Photodynamic therapy（PDT）is a method of diagnosing and treating various types of tumors through a photochemical reaction between photosensitizers（PS）,light,and oxygen.PDT has attracted wide attention in recent decades due to its unique advantages such as low invasibility,good selectivity and no cumulative toxicity.The selection of photosensitizer is very important in the process of photodynamic therapy.Platinum diimine complexes is a kind of biradical metal complex with unique electronic structure and rich oxidation-reduction properties.It has a high singlet oxygen yield under red light irradiation,and has a good inhibitory effect on the proliferation of cancer cells.It is a promising photodynamic drug.Photodynamic therapy mainly relies on the generation of singlet oxygen to induce apoptosis of cancer cells.Since singlet oxygen has the characteristics of short life span and short action distance,and mitochondria are the main organelles regulating apoptosis,it may be an effective approach to design mitochondria-targeted photodynamic therapy drugs to improve the activity of photodynamic therapy so as to improve its anti-tumor efficacy.Triphenylphosphonium（TPP）is a lipophilic cation targeted by mitochondria.In this paper,a triphenylphosphonium modified platinum phenylenediimine complex Pt-TPP was designed and synthesized,and the ability of Pt-TPP complex to produce singlet oxygen was investigated,The effects of the complex Pt-TPP and its drug-carrying nanoparticles on the proliferation of cancer cells and normal cells under light were also studied.（1）Using 4-nitro-o-phenylenediamine as raw material,triphenylphosphonium（TPP）modified o-phenylenediamine ligand was obtained through Boc protection,nitro-reduction,amideation reaction and de-BOC protection,and a new complex Pt-TPP was obtained from this ligand.The composition and structure of the ligands and complexes were characterized by infrared spectroscopy,electrospray mass spectrometry,elemental analysis,hydrogen nuclear magnetic resonance spectroscopy and UV-visible absorption spectroscopy.（2）Using 1,3-diphenyl isobenzofuran as a fluorescence indicator,the singlet oxygen production capacity of the complex Pt-TPP was explored by means of fluorescence spectrophotometer.The results show that Pt-TPP can effectively produce singlet oxygen.（3）The complex Pt-TPP was loaded on the magnetic nanoparticle（Fe₃O₄/R6G）@Si O₂-APTES to obtain drug-carrying nanoparticleⅠ,and the complex Pt-COONa was loaded on the magnetic nanoparticle（Fe₃O₄/R6G）@Si O₂-APTES-TPP to obtain drug-carrying nanoparticleⅡ.The loading rates of two kinds of drug-carrying nanoparticles were determined by ultraviolet visible absorption spectra.It was found that the drug loading rate of drug-carrying nanoparticleⅠwas 8.3%and that of drug-carrying nanoparticleⅡwas 8.8%.（4）The effects of the complex Pt-TPP and its drug-carrying nanoparticles on the proliferation of cervical cancer cells Hela cells and human normal liver cells HL-7702cells under light and no light conditions were studied by MTT method.It was found that the studied a platinum diimine complex had almost no damage to human normal cells HL-7702,but showed obvious photodynamic activity to Hela cells.In addition,it was found that the TPP modified platinum complex significantly improved the photodynamic activity of the complex,and the magnetic composite nanoparticles carried the complex will further improve the photodynamic activity.In addition,it was found that the TPP modified platinum complex or nanoparticles can significantly improve the photodynamic activity of drug-loaded composite nanoparticles.