| In recent years,photodynamic therapy（PDT）has important application prospects in the treatment of new malignant tumors because of its advantages of good selectivity,less systemic damage and easy control.The selection and use of fluorescent dyes as photosensitizers in this therapy is critical.Boron-dipyrromethene（BODIPY）derivatives are a class of important organic dyes that have been widely used in bio-imaging and cancer treatment.And they have advantages of large molar extinction coefficient,high fluorescence quantum yield,good photo-stability and easy modification.In this article,three novel indole-BODIPY photosensitizers were developed and applied for photodynamic therapy in cells and zebrafish.The main research contents are divided into four chapters as follows.Three new structures of indole-BODIPY dyes were designed and synthesized.Firstly,indole-containing morpholine moiety was linked to BODIPY core to synthesize a novel BODIPY fluorescent dye（BDP-Lys）through“one-pot”reaction.Secondly,iodine atom was introduced into the 2,6-position of BDP-Lys dye through radical substitution reaction,and IBDP-Lys and I2BDP-Lys photosensitizers were prepared.Finally,the near infrared photosensitizer IMBDP-Lys was successfully synthesized through Knoevenagel condensation reaction.A series of compounds were confirmed by 1HNMR spectra and high resolution mass spectrometry.The ISC process of indole-BODIPY dyes BDP-Lys,IBDP-Lys and I2BDP-Lys were explores.It was reasonably explained through theoretical calculation that the inhibition ISC process of fluorescent dyes BDP-Lys was caused by largeΔEST.Therefore,the iodine-free fluorescent dye BDP-Lys cannot effectively generate singlet oxygen.Introducing one iodine atom can promote the ISC process,while two iodine atoms can further strengthen the ISC effect.The theoretical and experimental results are consistent.In addition,an iodine atom-substituted photosensitizer IBDP-Lys can balance the production of singlet oxygen and biocompatibility in cancer treatment,and has good application effects in cells and zebrafish.A lysosome-targeted near-infrared photosensitizer IMBDP-Lys was constructed based on photosensitizer I2BDP-Lys.The photosensitizer IMBDP-Lys has a high singlet oxygen efficiency of 48.3%in dichloromethane.Two lysosomal targeting groups,morpholine,significantly improve the biocompatibility of photosensitizer.In addition,two-photon fluorescence imaging technology could be effectively applied to zebrafish,reducing the damage to biological tissues.During photodynamic therapy,reactive oxygen species（ROS）can induce apoptosis of tumor cell and effectively inhibit the migration of A549 cells within48 hours.Photosensitizer IMBDP-Lys showed good photodynamic therapy potential in cells and zebrafish. |
