Peryleneimide Near Infrared Photothermal Conversion And Antitumor Performance

Cancer is one of the biggest threats to human life and health.The current clinical treatment methods,such as surgery,radiotherapy and chemotherapy,all have obvious shortcomings,such as narrow application scope,high toxic and side effects,and difficult to be completely cured.Therefore,there is an urgent need to develop new therapeutic means to coordinate the treatment of malignant tumors.In recent years,photothermal therapy has attracted wide attention due to its advantages such as high anticancer efficiency,low toxicity and minimally invasive.The core of photothermal therapy lies in the development of photothermal conversion materials.The ideal photothermal materials have high molar extinction coefficient,good water solubility,light stability and low dark toxicity in the near infrared(NIR)region.The present photothermal conversion materials can be divided into inorganic nanomaterials and organic molecules.Inorganic materials are generally facing the problems of poor biocompatibility,high toxicity and difficult structure regulation.In contrast,organic molecules have the advantages of better biocompatibility,low toxicity,easy metabolism in organism and easy structure regulation.Peryleneimide(PDI)derivatives have a large delocalized electronic structure,strong absorption in the visible region,robust molecular structure,easy to modify and synthesize,and are potential excellent photothermal conversion materials.In this thesis,novel PDI derivatives with high photothermal conversion efficiency and good photostability were designed and synthesized,and their photophysical properties and anti-tumor properties were studied in depth.The main research contents of this thesis are as follows:1.Design of a composite nanomaterial based on thionated peryleneimide and the study on its photothermal antitumor performance.Development of organic molecules with high photothermal conversion efficiency(PCE)in the near-infrared(NIR)window is a vital yet challenging topic in the field of photothermal therapy.A series of thionated perylenediimides(PDI-4CHA-S)derivatives have been synthesized by replacing carboxylic oxygens in imides with sulfur atoms,providing chances to unravel the effect of thionation on the photophysical properties toward photothermal agents(PTAs)with high PCE.In the presence of the electron-donating substituents at the bay-position,sulfur atoms participate in the intramolecular charge transfer(ICT),which induces remarkable redshifl in the absorption maximum.Meanwhile,the ICT together with the heavy atoms effect of sulfur atoms promotes the intersystem crossing(ISC),resulting in the generation of the active oxygen species(ROS)upon photoexcitation.Interestingly,the quantum yield of ROS decreases with increasing the number of S-substitutes,which is the resultant of the attenuated ICT in the case of multiple S-substitution.Overall,the promotion in ISC due to thionation is negligible compared to the quenching of the radiation transition and enhancement of the absorption coefficient caused by ICT,hence the energy of the excited PDI-4CHA-S molecules is depleted mainly in the form of heat,leading to the ultrahigh PCE of 88.0%under 808 nm laser irradiation.The trithionated PDI-4CHA-3S performs surprisingly high PCE in the second near-infrared(NIR-Ⅱ)window(1064 nm)in particular.The superior photothermal effect and excellent photostability of the thionated PDI derivative provide them promising photothermal agents for NIR photothermal therapy.2.Preparation of J-aggregation of peryleneimide derivatives and study on its near-infrared photothermal conversion performance.PDI molecules have a large π-conjugated planar structure and are prone to aggregate in aqueous solution due to the strong intermolecular interactions including π-π interactions and hydrogen bonding.The formation of aggregates has a great influence on the photophysical properties of PDI molecules such as absorption and fluorescence,which greatly affects the photothermal conversion performance.Accordingly,we have bay-positions of PDI with 4-amino-trianiline electron-donating group(PDI-TAP)to induce strong ICT interaction with the PDI skeleton,resulting in large redshift of absorption and strong fluorescence quenching.Furthermore,PDI-TPA was coated inside silica nanocapsules(SNCs)to form J-aggregation.The external hydrophilic groups make the SNC disperse stably in aqueous solution,which helps solving the problem of poor water solubility of organic molecules.The formation of J-aggregation is conducive to further redshift of absorption spectrum and quenching of fluorescence,which will greatly improve the photothermal conversion efficiency.Subsequently,it showed good photothermal conversion effect and photothermal stability under 808 nm laser irradiation,which provided a new possibility for the preparation of photothermal diagnosis and treatment agent.