Construction Of Near-infrared Second Window Photo-responsive Ceria-based Nanotherapeutic Agent And Its Multifunctional Tumor Therapy

Phototherapy（photodynamic and photothermal therapy）is a method that utilizes Near-Infrared light to excite photosensitizers to generate reactive oxygen species or photothermal agents to generate hyperthermia to kill tumor cells,thereby achieving tumor treatment.Due to its non-invasive and highly selective characteristics,this method shows great advantages and application prospects in the treatment of tumors.Compared with the first Near-Infrared window（NIR-I）light,the second Near-Infrared window（NIR-II）light has a stronger penetrating ability,however,the clinical application of phototherapy is still limited by its tissue penetration.To achieve a better treatment effect,a combination of multiple treatment modes can usually be adopted.Sonodynamic therapy is the use of ultrasonic radiation sonosensitizers to generate reactive oxygen species and kill tumor cells.Compared with photodynamic therapy,it has the obvious advantages of strong tissue penetration and good safety.As a new treatment modality,sonodynamic therapy has both non-invasive and deep tissue penetration ability and is considered to be a promising tumor treatment method.However,the therapeutic effect of sonodynamic will be limited by the hypoxic microenvironment of the tumor and its quantum yield,which will weaken the therapeutic effect,so the combined treatment strategy is particularly important.Based on this,this paper designed and synthesized an oxygen vacancy-rich cerium oxide nanomaterial,which was further modified with the lipopolysaccharide sodium hyaluronate（HA）to endow it with the ability to actively target the CD44 receptor and a good biological phase.Construction of a nanoplatform for second Near-Infrared window photoacoustic imaging-mediated sonodynamic enhanced photodynamic/photothermal combined therapy for tumor therapy.The details are as follows:Chapter 1:Current status of tumor therapy,radiotherapy,chemotherapy,chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,fluorescence imaging,photoacoustic imaging,commonly used tumor-targeting organic groups,defect materials types,applications,and introduction of cerium oxide properties and applications.Chapter 2:Oxygen-deficient Ce O_2-x was prepared by high-temperature reduction,and the Ce O_2-x@HA nanomaterials were modified by hyaluronic acid.It has excellent dispersibility and stability.Due to the introduction of oxygen vacancies in Ce O_2-x@HA,its forbidden bandwidth is reduced,which slows down the recombination of holes and electrons and efficiently converts the amount of light into heat energy.In addition,photogenerated electrons can catalyze oxygen molecules to generate O₂^·-,while holes in the valence band oxidize H₂O to generate·OH.Under the irradiation of NIR-II laser and US ultrasound,Ce O_2-x@HA not only exhibits excellent photothermal conversion effect and reactive oxygen species generation properties but also possesses the capability of high-resolution photoacoustic imaging.It is a multifunctional photoacoustic sensitizer with potential photothermal,photodynamic,and sonodynamic applications.Chapter 3:The Ce O_2-x@HA nanomaterials obtained by the modification of Ce O_2-x with biological polysaccharide hyaluronic acid were used to further explore their anticancer effects and biocompatibility in vitro and in vivo.In vitro and in vivo experiments verified that Ce O_2-x@HA nanomaterials can actively target and recognize CD44 receptors overexpressed by tumor cells and accumulate in tumor tissue sites.Under the radiation of external NIR-II light and ultrasound,it exhibits strong photothermal heating,reactive oxygen species generation,and photoacoustic imaging capabilities.In vitro and in vivo experiments showed that 1064 nm laser and US ultrasound irradiation to 4T1 tumor-bearing mice according to the optimal treatment time point mediated by photoacoustic imaging achieved the optimal tumor treatment effect,effectively eliminating tumors in the mice.H＆E staining proved that Ce O_2-x@HA did little damage to major organs,and the blood biochemical indexes were all within a reasonable range.Therefore,Ce O_2-x@HA nanomaterials realize SDT-enhanced PTT/PDT synergistic therapy,which has a promising biological application.