Synthesis And Application In Tumor Photo-Therapy Of Novel Fluorobron Dipyrrole (BODIPY) Compounds

Boron-dipyrromethene(BODIPY)compounds are an important kind of fluorescent dyes.Because of their excellent optical properties,they can be used for photothermal and photodynamic therapy of tumors.However,there are still many problems in the application.For example,a single substance does not have multiple functions such as PTT and PDT at the same time,it is difficult to realize the simultaneous excitation of photosensitizers by a single wavelength laser,and the structure-activity relationship between BODPY and PTT/PDT is not clear.It hinders the further development of BODIPY in the field of phototherapy.In our research,we designed and successfully synthesized 9 new BODIPY near-infrared dyes,and studied the structure-activity relationship between BODIPY and PTT/PDT in detail.The results showed that the introduction of electron-donating groups into the active sites 3 and 5 of BODIPY core had higher PTT efficiency and PDT efficiency than the introduction of halogen atoms into active sites 2 and 6.This is mainly due to the extension of the conjugated chain and the PET effect.On this basis,three BODIPY molecules with excellent PTT and PDT performance--BDPC-biⅠ,BDPC-biⅡ and BDPI-biⅡ were screened out,and BDPX-M/RGD NPs liposomes were obtained by using amphiphilic DSPE-PEG2000-RGD and lecithin to encapsulate BDPX-M molecules.Using Hela cells as a model,cytotoxicity test,phototherapy effect test,cell uptake ability test and intracellular ROS generation ability test were carried out.Finally,using tumor-bearing mice inoculated with Hela cells as a model,the fluorescence imaging ability in vivo,tumor targeting ability and combined treatment ability of BDPC-biⅡ NPs/RGD were tested.The results showed that nanoparticles had good water solubility and biocompatibility,tumor targeting,diagnosis,and PTT/PDT synergistic treatment effects,in which the photothermal conversion efficiency:42.76 %,A/A0: ≈ 0.05.In short,we obtained BDPC-biⅡ/RGD NPs with excellent photothermal and photodynamic effects under single excitation of 808 nm laser.The NPs showed good water solubility and biocompatibility,which can be used as photothermal and photodynamic synergistic therapy excellent drugs for tumors.This provides a research direction for the design and construction of BODIPY nanoparticles for tumor phototherapy.