Development And Application Of Novel Organic Small Molecule Photosensitizers

Cancer is a major disease threatening human health.Traditional cancer treatment methods,including chemotherapy,radiotherapy and surgery,are invasive considering that they often bring various adverse side effects to cancer patients during the treatment process due to the systemic drug administration or excessive radiotherapy.Photodynamic therapy（PDT）is an emerging cancer treatment method,which can generate a large number of reactive oxygen species（ROS）through photosensitizer（PS）under light irradiation and then kill cancer cells at the site of the tumor.The method possesses the advantages of low invasiveness,negligible drug resistance and so on.A large number of PSs have been constructed in recent years.However,most of them have following typical shortcomings,such as low quantum yield of fluorescence and ROS in water,small Stokes displacement,etc.In particular,some PSs display aggregation-caused quenching（ACQ）effect,leading to the low ROS quantum yield,or are in an"always on"mode,resulting in unnecessary damage to normal tissues.Therefore,a new and efficient PSs is desperately needed to promote the development of PDT.Based on the skeleton of tetraphenylethylene（TPE）,which holds aggregation-induced emission（AIE）effect,two kinds of novel organic small molecule PSs were synthesized and their photosensitive properties were studied.The specific work is as follows:（1）By covalentating TPE with diaryl ethylene（DAE）via Suzuki coupling reaction,the DAE-TPE featuring rubost AIE effect was prepared.Then,DAE-TPE was wrappd with F-127 to afford DAE-TPE nanoparticles（NPs）.After that,the photosensitive properties of DAE-TPE NPs were tested using 9,10-anthracyl-bis-（methylene）dimalonic acid（ABDA）as a singlet oxygen（¹O₂）trapping agent in buffer solution,and further verified by MTT assay,live/dead cell staining assay and apoptosis detection assay.The experiment results demonstrated that under the irradiation of520 nm light,the photosensitivity of“Opened”form（OF）of DAE-TPE NPs is extremely weak.In sharp contrast,the photosensitive capacity is significantly enhanced when DAE-TPE NPs was converted to“Closed”form（CF）with UV irradiation,resulting significant phototoxicity to He La cells.（2）Using TPE as AIE skeleton,two kinds of AIE PSs,TPE-SF and TPE-2SF,were constructed by covalently linking TPE withβ-hydroxyimide boron complex.The corresponding NPs were prepared separately by encapsulating it with DSPE-PEG-Mal.In order to further enhance their cellular uptake ability,the surface of the NPs was modified with cell-penetrating peptide TAT-SH to obtain the corresponding TPE-SF NPs and TPE-2SF NPs,respectively.By comparing the degradation rate of ABDA at 465 nm,it was found that the photosensitivity of TPE-2SF NPs is remarkably higher than that of TPE-SF NPs.As such,the PDT performance of TPE-2SF NPs was further evaluated by a series of cell experiments,such as MTT assay,live/dead cell double staining assay,and cell detection apoptosis assay.The results showed that TPE-2SF NPs have good biocompatibility and show significant phototoxicity to He La cells under the irradiation.