PEGylated Semiconducting Oligomers For Development And Applications Of Cancer Theranostics

Second near-infrared window（NIR-II）phototheranostics has the advantages of high tissue penetration depth,biosafety,imaging sensitivity,and treatment accuracy.Organic nanomaterials have shown great potential in cancer theranostics because of their advantages including good biocompatibility,high absorption coefficient,multifunctionality.Therefore,organic nanomaterials have been widely used in NIR-II phototheranostics.However,they still have some limitations in the field of NIR-II phototheranostics.For example,most nanomaterials can only be cleared out of body through hepatobiliary metabolism due to their large size,which may retain in the body for a long time,causing potential long-term toxicity.In addition,due to the shortcomings of phototherapy such as low tissue penetration depth,high dependence on oxygen or the impact of heat shock protein,any single modality of phototherapy has their own limitations in the cancer treatment.It is of great significance to develop combination therapeutic systems.In order to solve the above problems,this paper constructs two different NIR-II phototheranostics based on semiconducting oligomers（SOs）for tumor imaging and treatment:（1）A Renal-Clearable PEGylated Semiconducting Oligomer for NIR-II Fluorescence Imaging of Tumor.We design a water-soluble PEGylated SO（PSO）for NIR-II fluorescence imaging of tumor.PSO is composed of a hydrophobic SO backbone which can emit NIR-II fluorescence signal,and four poly（ethylene glycol）（PEG）chains which provide water solubility for SO.PSO has good water solubility due to the modification of PEG.PSO has near-infrared absorption,and its emission wavelength could be tailed to more than 1300 nm,and the maximum emission was found at 1000nm.PSO can effectively be internalized into 4T1 cells,and exhibits good biocompatibility towards4T1 cells.PSO can accumulate into tumor via passive targeting and its NIR-II fluorescence signal may delineate the tumor region.The obvious NIR-II fluorescence signals in the kidney and bladder of mice after treatment of PSO clearly indicate that PSO can partially be metabolized via renal clearance.This study provides a method for synthesizing renal-clearable NIR-II fluorescent SO for tumor imaging.（2）DHA-loaded semiconducting oligomer nanomaterials for photothermal/enhanced chemodynamic combination therapy.We have developed a semiconducting oligomer nanomaterial（DHA@Fe PSOD）for NIR-II fluorescence imaging-guided photothermal/enhanced chemodynamic therapy.Based on the SO synthesized in the previous chapter,we modify the side chains of the SO with both PEG chains and dopamine,which endows SO with the capability of chelating Fe³⁺.After chelating Fe³⁺,the formed nanoparticles further load dihydroartemisinin（DHA）through hydrophobic interaction to obtain the final nanoparticles DHA@Fe PSOD.Under near-infrared laser irradiation,DHA@Fe PSOD shows good NIR-II fluorescence signal and photothermal property.At the same time,DHA@Fe PSOD can catalyze H₂O₂into hydroxyl radical in the presence of GSH,achieving chemodynamic therapy.Cell studies show that DHA@Fe PSOD can be effectively internalized by tumor cells and kill them by photothermal/chemodynamic therapy under laser irradiation.In vivo studies indicate that DHA@Fe PSOD can accumulate into tumor and light the tumor up via its NIR-II fluorescence signa.