Application Of BODIPY Photosensitizer In Photodynamic Therapy For Tumor

Photodynamic therapy(PDT)is an emerging technology to treat cancer that relies on light-mediated photosensitizer(PS)activation to produce reactive oxygen species(ROS).When the tumor sites are irradiated,PS can be transited from the ground state to the excited state,subsequently generating singlet oxygen through the intersystem crossing and internal chemical reactions.The singlet oxygen enables to selectively kill the surrounding tumor cells and thus achieves disease treatment.Compared to those traditional techniques of tumor therapy,PDT has the advantages of low toxicity,non-invasiveness,and fewer side effects.Therefore,the development of PS that contains a high singlet oxygen quantum yield has become a hot research topic in recent years.Among the different kinds of PSs,boron dipyrromethene(BODIPY)fluorescent dye has the characteristics of high fluorescence quantum yield and easy functionalization,which has drawn considerable attention from chemists and medical workers.Here,we designed and synthesized a series of phenol,thiophenol,selenophenol,and tellurol functionalized BODIPY derivativesmodified by heavy atom iodine,further using them for PDT against tumors.The detailed experimental work was as follows:(1)In this paper,four monomers of BODIPY-X(X = O,S,Se and Te)modified with iodine had been prepared to realize the wavelength adjustment of BODIPY derivatives.The structures of BODIPY-X derivativeswere determined by NMR and MS.The monomerswere characterized by UV,fluorescence,electrochemistry and theoretical calculations.From oxygen,sulfur,selenium to tellurium,the UV absorption and fluorescence emission of BODIPY-X showed a significant red shift.Among them,BODIPY-Te could reach the near-infrared region.The F127/BODIPY-X were obtained by monomers wrapped with amphiphilic polymer Pluronic F-127,which improvesd the hydrophilicity of the photosensitizers.The morphology was characterized by dynamic light scattering and transmission electron microscopy,and the particle size was between 150-200 nm.(2)The cytotoxicity of F127/BODIPY-X was determined by MTT;the distribution of F127/BODIPY-X in cells was studied by cell phagocytosis;the singlet oxygen probe was used to detect the singlet oxygen production of F127/BODIPY-X.All thoes results showed that F127/BODIPY-X could enter the cytoplasm;display mo dark toxicityin the absence of lightand the dose-depended cytotoxicity under light conditions;F127/BODIPY-Te has the highest efficiency in producing singlet oxygen with light irradition.A series of in vitrobiological experiments had shown that F127/BODIPY-Te had a better cancer photodynamic therapy effect.Finally,by analyzing the biochemical indicators of the important organs of the treated mice,the indicators were generally within the normal range,which proved that F127/BODIPY-X had good biological safety.