Synthesis Of Near-Infrared BODIPY Nanoparticles And Application In Tumor Phototherapy

Supramolecular organic dye aggregates are useful building blocks for the design of the next-generation phototherapeutic agents(PTAs)by virtue of their intrinsic advantages such as well-defined assembled nanostructure,attractive photophysical properties,good reproducibility and potential clinic translation.However,how to develop high-performance photosensitizers that can be excited by low power lights and use them in high-efficiency photodynamic therapy has always been a difficult problem in the field of tumors.Herein,we develop a simple and efficient supramolecular self-assembly strategy via the supramolecular interaction of carboxyl-containing photosensitizer and tris(hydroxymethyl)aminomethane(Tris)to promote the formation of nano aggregates and obtain zwitterionic near-infrared nano photosensitizers.It exhibits good water-solubility,ultrahigh photostability,and pH-responsive behavior.More importantly,this nano-photosensitizer can effectively generate singlet oxygen under the irradiation of LED lights(660 nm,50 mW cm-2),thereby exhibiting superior anti-tumor photodynamic activity.This strategy thus provides an insight into the development of advanced PTAs for efficient photo-induced tumor therapy.The specific research contents of this thesis are summarized as follows:Chapter 1 briefly summarizes the current status of tumors and treatment methods,the development and mechanism of photodynamic therapy,the application of zwitterionic polymers in tumor treatment,and the application of Tris in nano-assembly.On this basis,the design ideas and research content of this paper are clarified.Chapter 2 reports the application of Tris in the self-assembly study of carboxyl-containing photosensitizers.Firstly,photosensitizer Ce6 was selected as the model compound,and the nano photosensitizer Ce6@Tris was formed by self-assembly using weak interactions(such as π-π interaction,electrostatic interaction,etc.).Based on this research,we designed and synthesized boron dipyrromethenes(BODIPY)derivatives containing carboxyl groups,and constructed nano-photosensitizers BDP-C16@Tris and BDP-F,7@Tris.Then the physical and chemical properties of the nano-photosensitizers were characterized including morphological characterization,ultraviolet-visible absorption spectrum,fluorescence emission spectrum,singlet oxygen quantum yield,solubility in water and stability,etc.The results show that BDP-F17@Tris has strong near-infrared absorption,suitable particle size,even dispersion,excellent stability,and good solubility in water.In addition,we investigated its assembly behavior and release under different pH conditions.Chapter 3 describes the activity of nano photosensitizers at the cytological level.The cellular uptake,subcellular co-localization,light induced intracellular ROS production,cytotoxicity and cell apoptosis were investigated.The experimental data show that BDP-C16@Tris and BDP-F17@Tris can be activated by low-power LED lights(660 nm,mW cm-2)to exert its photodynamic activity,thereby effectively killing tumor cells.Chapter 4 demonstrates the anti-cancer efficacy with photodynamic therapy in vivo.The results show BDP-F17@Tris has a good anti-tumor effect with photodynamic therapy via the direct injection of the drug into tumors.Chapter 5 reports the design and synthesis of BODIPY carboxylic acid derivatives cap-BDP and cap-BDP-F17.Then they were linked with the zwitterionic polymer polycarboxybetaine(PCB)to synthesize a new type of zwitterionic photosensitizer PCB-BDP.In addition,we designed non-zwitterionic photosensitizer PEG-BDP-F17 as a contrast compound.Chapter 6 summaried the thesis.