Molecular Engineering To Red-Shift The Absorption Band Of AIE Photosensitizers And Improve Their ROS Generation Ability

Cancer has a high morbidity and mortality rate and is one of the most difficult diseases to cure.There are about 14 million new cases worldwide every year.Traditional cancer treatment methods mainly include surgery,chemotherapy,and radiotherapy.But these methods can not only kill cancer cells but also cause great damage to normal cells,while having strong side effects on the human body.Therefore,the development of new safe and effective cancer drugs is imminent.Unfortunately,the development of drugs,especially cancer drugs,is a long,high-risk,and expensive process because it involves many stages of drug screening and clinical trials.Therefore,the development of new safe and effective cancer therapies is imminent.In recent years,photodynamic therapy（PDT）has gradually attracted attention in the field of cancer treatment due to its advantages of low toxicity,minimal invasiveness,and repeatable treatment.PDT uses photosensitizers to generate cytotoxic reactive oxygen species under the irradiation of light of appropriate wavelengths to treat tumors.Singlet oxygen plays a major role in inducing cell death.Traditional photosensitizers have a rigid structure,which is easy to aggregate in the physiological environment,resulting in fluorescence and photodynamic quenching,which reduces the anti-tumor effect of PDT.In recent years,a new photosensitizer,aggregation-Induced Emission（AIE）,which is different from traditional photosensitizers,has received widespread attention in anti-tumor,referring to a unique physical phenomenon that fluorescent molecules fluoresce more strongly in the aggregated state than in the dispersed state.Compared with the traditional photosensitizer of aggregation-caused quenching（ACQ）,AIE photosensitizer better avoids quenching in the aggregation state,thereby having stronger fluorescence and better photodynamic effect,so it has broader application prospects in anti-tumor.However,the current application of AIE-PSs in tumor therapy is still limited,one of the reasons is that the light absorption wavelength of AIE-PSs is relatively short,which seriously hinders their application in PDT for deep tumor tissues.Therefore,the development of AIE-PSs with long-wavelength absorption can effectively improve their role in the field of antitumor PDT.In this project,four new AIE-PSs were developed.Through molecular structure modification,the light absorption peaks of these AIE-PSs were moved from 478 nm to 540 nm with a tail extending to 700 nm.Simultaneously,their emission peaks were also shifted from 697 nm to 779nm with a tail extending beyond 950 nm.Importantly,their singlet oxygen quantum yields were increased from 0.61 to 0.89.One of the best photosensitizers,TBQ,was also successfully applied to image-guided PDT of BALB/C mice bearing 4T1 breast cancer under red light（605±5nm）irradiation,with IC₅₀ less than 2.5μM.Simultaneously,animal experiments have verified that TBQ has been successfully applied to image guided photodynamic anticancer therapy under red light illumination This study indicates that increasing the number of electron acceptors in the molecule can redshift the light absorption bands of AIE-PSs more effectively than increasing the number of electron donors;extending theπ-conjugation of electron acceptors will redshift the light absorption and emission bands,increase the maximum molar extinction coefficient and enhance the ROS generation ability of AIE-PSs,thus providing a new strategy for the design of AIE-PSs for deep tissue PDT.