Construction And Application Of Mitochondria-targeted AIE-type Photosensitizers

In recent years,photosensitizers with the effect of aggregation-induced emission(AIE)have attracted extensive attention in photodynamic therapy guided by fluorescence imaging due to their strong luminescence characteristics,excellent photostability,good biocompatibility,and enhanced ability to generate singlet oxygen in the state of aggregation.In this thesis,the properties of two AIE photosensitizers with red emission and their anticancer and antibacterial effects by photodynamic therapy were studied.An activable chemical prodrug based on AIE photosensitizer was designed and synthesized for in-situ monitoring of the release of chemotherapy drugs in cancer cells and combined diagnosis and treatment of cancer cells.1.The photosensitive properties of two AIE molecules with red emission,TPE-QN and TPE-DQN,were studied systematically.By extending the conjugated structure of the molecule,the luminescence of TPE-DQN can be effectively transferred to the near infrared region,and the singlet oxygen production efficiency can be further improved.The quantum yields of singlet oxygen for TPE-QN and TPE-DQN are 76.8%and 83.3%,respectively.Importantly,these AIE photosensitizers can selectively target cancer cell mitochondria without any additional targeting ligands.Under the irradiation of low power white light source(25 mW cm-2),the compounds showed extremely high photodynamic killing effect on cancer cells.Among them,TPE-DQN was used to inhabit tumor growth of mice,and achieved good results.In addition,the two AIE photosensitizers can also selectively label Gram-positive bacteria.With its light-sensitive characteristics,it can achieve up to 96%and 99%antibacterial effect.2.Based on AIE photosensitizer,a case of esterase activated chemical prodrug TPEQO-Cbl was designed and synthesized by coupling AIE photosensitizer with chlorambucil.In the presence of esterase,TPE-QO-Cbl can be effectively decomposed to produce chlorambucil and photosensitizer TPE-QO with AIE characteristics.TPE-QOCbl has excellent selectivity and sensitivity to esterase,and its detection limit is 2.381×10-5 U mL-1.Due to its good biocompatibility,TPE-QO-Cbl can effectively enter cancer cells,and then be decomposed by esterase in cells.Meanwhile,AIE photosensitizer and chlorambucil are released for combined treatment.At the same time,the fluorescence recovery of the photosensitizer TPE-QO can also be used to report the release degree of photosensitizer and chlorambucil.Further application of TPE-QO-Cbl to the tumor model of mice showed that compared with the photosensitizer and chemotherapy alone,TPEQO-Cbl has obvious inhibition of tumor in mice.