Synthesis Of BBTD-based D-A Type NIR-Ⅱ Photothermal Agent And Its Cancer Theranostics Study

As the second leading cause of death in the world,cancer has been threatening people’s life and health.With the increasing demand for accurate early diagnosis and safe treatment of tumors,non-invasive optical theranostics has attracted research interest.Theranostics creatively integrates diagnostic imaging and therapy into one platform,witnessing the transformation of medicine from traditional to modern,personalized,and precise.At present,the research of photo-theranostics reagents is still mainly focused on the first near-infrared region(NIR-I,700-1000 nm),in contrast,light in the second near-infrared region(NIR-Ⅱ,1000-1700 nm)shows great application potential in optical theranostics due to its minimal tissue self-fluorescence level,reduced tissue absorption and scattering,and deep tissue penetration.Among them,NIR-Ⅱ organic small molecule photothermal agents with donor-acceptor(D-A)structure show advantages in photothermal therapy because of their good photobleaching resistance,large Stokes shift and easy functionalization modification.However,in the existing NIR-Ⅱ theranostics agents,polymers still predominate,and small organic molecules are limited.Therefore,starting from the D-A-D basic molecular skeleton,this thesis designed and synthesized the NIR-Ⅱ organic small molecule photothermal agent with long wavelength absorption and emission by selecting strong acceptor benzodithiadiazole(BBTD)as the nucleus,introducingπ-bridge and another donor to enhance D-A interaction,and explored its photothermal therapeutic effect under the guidance of photoacoustic imaging/photothermal imaging.The main research content of this thesis is as follows:(1)A D-π-A-π-D compound BTTP was synthesized by Suzuki/Stille coupling reaction using benzodithiadiazole as a strong electron acceptor and trianiline-pyridine as an electron donor.After that,the molecular structure of BTTP was analyzed by NMR and MS data to prove its successful preparation,and its optical properties were investigated by ultraviolet absorption spectrum and fluorescence emission spectrum.(2)In order to improve the water solubility and biocompatibility of BTTP,nano-photothermal agent BTTP NPs were synthesized by packaging BTTP into the amphiphilic block polymer Pluronic F127.The morphology of BTTP NPs was characterized by dynamic light scattering and transmission electron microscopy.It was proved that BTTP NPS were uniformly dispersed and stable in aqueous solution.Then the photophysical properties of the nanoparticles were studied.It was found that the ultraviolet absorption spectrum of the nanoparticles was redshifted by about 90nm,and the fluorescence emission wavelength reached the NIR-Ⅱ region.In addition,the photothermal conversion ability and photothermal stability of BTTP NPs as a kind of photothermal agents were investigated.The results showed that under the irradiation of 980 nm laser(1.0 W/cm~2),the photothermal conversion efficiency of BTTP NPs was 46.7%,and it could still increase the similar temperature after 5hot-cold cycles,showing good photothermal conversion potential.The dark and phototoxicity of BTTP NPs were investigated using He La cells.To evaluate the theranostics potential of BTTP NPs,we examined its photoacoustic/photothermal imaging effects in tumor-bearing mice.