Design,Synthesis,and NIR-Ⅱ Phototheranostic Applications Of Organic Semiconducting Small Molecules

Fluorescence imaging conducted in the second near-infrared(NIR-II)window is a new diagnostic technology,which has become a research hotspot in recent years.Because biological tissue has low absorption,photon scattering is suppressed and tissue self fluorescence is weak in second near-infrared window,compared with NIR-I fluorescence imaging,NIR-II fluorescence imaging can display more abundant biological information with deeper penetration depth and higher signal to noise ratio.Phototherapy,such as photothermal therapy or photodynamic therapy,has received extensive attention as a new means of tumor treatment.Photothermal therapy(PTT)has the advantages of non-invasiveness,high spatial and temporal resolution,good therapeutic effect and easy operation.Photodynamic therapy(PDT)has the advantages of less invasion,small side effects,and controllable time and space.Organic semiconducting small molecules have the advantages of low molecular weight,easy metabolism,high photostability and biological stability,and have great application prospects in biological imaging.The combination of NIR-II fluorescence imaging and optical therapy provides a new idea for precise diagnosis and treatment of cancer.However,although a single mode of phototherapy can kill tumors to a certain extent,it often cannot completely eliminate tumors,leading to recurrence and metastasis.Based on this,this thesis focuses on the design and development of organic semiconducting small molecule materials,and explores their applications in NIR-II fluorescence imaging mediated photothermal and photodynamic therapy.The main research contents are as follows:(1)Organic semiconducting small molecule nanoprobe for NIR-II fluorescence imaging-guided photothermal therapyThree kinds of organic semiconducting small molecules were synthesized by controlling the donor unit and π bridge unchanged.After the optical performance characterization,the small molecule with the best NIR-II fluorescence performance was optimized,and the water dispersible nanoprobe was prepared by nanoprecipitation method.The experimental results show that the nanoprobe has good photostability,photothermal performance and NIR-II fluorescence imaging effect.Cell experiments showed that the nanoprobe can be efficiently absorbed by cancer cells and emit strong NIR-II fluorescence,and can effectively kill cancer cells under near-infrared light irradiation.In vivo experiments showed that the nanoprobe had high accumulation in the tumor site,which could clearly depict the tumor profile through NIR-II fluorescence imaging.(2)Organic semiconducting amphiphilic molecule/Ce6 composite nanoprobe for NIR-II fluorescence imaging and photothermal/photodynamic combination therapyWe designed and synthesized amphiphilic semiconducting oligomers with NIR-II fluorescence properties,which were used to encapsulate the photosensitizer Ce6.Under laser irradiation,the nanoprobe not only shows obvious temperature rise effect,but also can produce singlet oxygen,which has good photodynamic performance.At the same time,the nanoparticles have good biocompatibility,photostability and NIR-II fluorescence imaging performance.The cell imaging experiment shows that the nanoprobe can be efficiently internalized by tumor cells,and has excellent photothermal/photodynamic combination therapeutic effect under laser irradiation.Compared with single mode phototherapy,this combination phototherapy has significantly enhanced the killing efficiency of cancer cells.In addition,in vivo experiments show that the nanoprobe can be highly enriched in the tumor site after tail vein administration,showing a good imaging effect in vivo.