Preparation And Properties Of Nir Triggered A-D-A Small Molecule Based Nanophotothermal Agents

Phototherapy(include photodynamic therapy(PDT)and photothermal therapy(PTT))is a newly developed tumor treatment method in recent years.It has attracted extensive attention due to their characteristics such as convenience,noninvasiveness,locally selective treatment,negligible drug resistance and minimized adverse side effect.The principle of phototherapy is based on the photochemical reaction of photosensitizers(photosensitizers and photothermal agents).After intravenous injection,the photosensitizer would be preferentially absorbed and accumulate in the tumor tissue.Upon photoactivation with laser at appropriate wavelengths,the photochemical reaction would occur,and the generation of cytotoxic species such as reactive singlet oxygen(¹O₂)and heat to induce apoptosis or necrosis of cancer cells.Among them,photosensitizer is one of the main factors that determine the efficiency of phototherapy.However,the conventional photosensitizers used for phototherapy are mostly activated by UV or visible light,which cannot pass through thick tissue due to the light absorption and scattering by biological tissues.The application of these UV or visible light PSs is limited to treating tumors on or just under the skin or on the lining of internal organs or cavities and is less effective when treating large and deep-seated tumors.Therefore,this thesis is focus on the design and preparation of near-infrared light(NIR)triggered high-efficiency photosensitizers and apply in phototherapy of tumor.The specific works are as follows:1.Hypoxia is a main feature of tumor,this property would affect the therapeutic efficiency of photodynamic therapy.In this study,a small organic molecule CPDT with acceptor-donor-acceptor(A-D-A)structure was used as a new photosensitizer.CPDT was co-precipitated with active targeting ligand(folic acid)introduced amphiphilic copolymer(FA-PEG-PBLA)to prepare a nanosensitizer(PTA-1)for tumor PDT/PTT combination therapy.It was found that PTA-1 exhibits high photothermal conversion efficiency(36.5%),after 5 cycles of laser irradiation,it showed good optical stability and obvious photothermal and photodynamic activity behavior.In mice vivo test shown that PTA-1 exhibit good enrichment ability for tumor tissues,after 808 nm laser radiation,PTA-1 showed obvious inhibition of tumor growth.2.In order to further improve the tissue penetration depth of phototherapy and therapeutic efficiency of tumors in large and deep tissues,in this study,a 880 nm triggered organic small molecule 3TT-IC-4Cl with an A-D-A structure was selected as the photothermal agent.3TT-IC-4Cl was co-precipitated with active targeting ligand(folic acid)introduced amphiphilic copolymer(FA-PEG-PBLA)to prepare a nanosensitizer(PTA-2)for tumor photothermal therapy.It was found that PTA-2exhibits high photothermal conversion efficiency(31.5%),after 5 cycles of laser irradiation,it showed good optical stability and obvious photothermal behavior.In vitro cell test showed that PTA-2 showed good biocompatibility,and after irradiation by 880 nm laser,PTA-2 showed obvious phototoxicity to tumor cells.