Amphiphilic Iodinated BODIPY Nanomaterials For Cancer Therapeutics Research

Cancer is a threat to human health,and how to carry out effective cancer diagnosis and treatment is a major challenge in the current biomedical field.Compared to traditional diagnostic and therapeutic methods,new medical treatment techniques such as fluorescence imaging,photodynamic therapy,and photothermal therapy have become hot spots for research due to their high selectivity,low toxicity,and noninvasiveness.Cancer theranostics allows for simultaneous diagnosis and treatment,as well as real-time monitoring of drug distribution,accumulation,and treatment efficacy,and re-optimization of the treatment plan based on its effectiveness.Therefore,the development of nanomaterials for efficient cancer theranostics is of great significance.Boron dipyrromethene(BODIPY)dyes have been widely studied in recent years because of their remarkable optical properties,ease of modification,and high biosafety,which make them stand out among many biomaterials.In this thesis,we have synthesized a series of NIR BODIPY nanomaterials with different optical properties and examined their capabilities in tumour diagnosis and therapy.The specific work is as follows:Part Ⅰ: In this dissertation,we designed and synthesized a series of amphiphilic iodinated BODIPYs with different electron donors(BDPC,BDPI,BDPN,and BDPJ).The structures of the four synthesized compounds were characterized by NMR and mass spectrometry.By density functional theory(DFT),UV-vis absorption spectroscopy,and fluorescence emission spectroscopy,it is found that the degree of molecular conjugation increases with the electron-donating ability of the substituent group,resulting in the red-shift of their absorption and emission spectra.Through the determination of the critical aggregation concentration,dynamic light scattering,and transmission electron microscopy,it was demonstrated that all amphiphilic BODIPYs can self-assemble in water to form spherical nanoparticles,and all of them except BDPI have good particle size stability.Subsequently,absorption and emission spectra of the self-assembled nanoparticles were probed and revealed the presence of anti-parallel Jaggregation due to hydrophilic chain and halo-bond interactions,with large red-shifts in both absorption and emission and a significant decrease in fluorescence quantum yields.Part Ⅱ: The imaging and phototherapeutic capabilities of nanoparticles formed by self-assembled NPs(BDPC NPs,BDPI NPs,BDPN NPs,and BDPJ NPs)were investigated.Firstly,the efficiency of singlet oxygen generation,photothermal conversion efficiency,photoacoustic imaging capability,and photobleaching resistance were investigated for four nanoparticles in aqueous solutions.Subsequently,due to the poor photobleaching resistance of the BDPI NPs,only BDPC NPs,BDPN NPs,and BDPJ NPs were subjected to cytological studies,including cellular internalization,cytotoxicity,synergistic therapeutic capacity,and singlet oxygen generation capacity.Finally,the imaging ability,anti-tumour effect,and biosafety of the three nanoparticles were investigated in vivo by constructing a 4T1 tumour-bearing mouse model.In vivo and in vitro experiments have proved that,under 808 nm laser irradiation,BDPN NPs exhibited excellent fluorescence/photothermal/photoacoustic multimodal imagingguided photodynamic/photothermal synergistic therapeutic capabilities,with high biological safety,whereas BDPC NPs and BDPJ NPs could not possess all the capabilities synchronously.