Studies On The Application Of Mixed Valence Tungsten-based Nanoparticles In Tumor Diagnosis And Treatment

Cancer is still not effectively controlled now adays,due to its high mortality,poor prognosis,easy to relapse and so on.At present,the commonly used methods for the treatment of cancer include surgery,radiotherapy,chemotherapy and immunotherapy.Surgery has some shortcomings,such as poor patient compliance,high surgical risk,easy recurrence and so on.The systemic side effect of chemotherapy is serious,which has a huge impact on patients.As tumor treatment methods developed in recent years,phototherapy utilizes the interaction of near-infrared light and light absorbents to produce high temperature an d reactive oxygen species,thus inducing the apoptosis of tumor cells.However,monotherapy is not effective,and is accompanied by serious side effect,recurrence and metastasis.In order to overcome the problems,the mixed valence tungsten oxide-based nanospheres(W₁₈O₄₉)were designed and synthesized.Using its good photodynamic effect,photothermal conversion ability,high atomic number and other characteristics to achieve tumor diagnosis and treatment,at the same time its combined anti-tumor mechanism was studied.The mixed valence tungsten based nanoparticles were prepared by solvothermal method.Ethanol was used as the reaction solvent.The reaction time was 20 h,the reaction temperature was 200℃,the reaction concentration was 15mmol/L,and the nanoparticles were homogeneous nanospheres with burrs.The particle size is about 200 nm,and the wavelength of 800～1800 nm has good absorption performance.The valence state of W exists in the form of W^（IV）,W^（V）and W^（VI）.The defective tungsten oxide W₁₈O₄₉has good phototherapy and radiosensitization performance,which provides an important material basis for follow-up phototherapy and combined therapy.The results of MTT assay showed that W₁₈O₄₉ had no obvious toxicity within the therapeutic concentration.There were no obvious changes in blood routine and biochemical indexes of mice after injection of W ₁₈O₄₉,and no pathological changes in H&E staining.It had good blood and tissue compatibility.W₁₈O₄₉ had excellent capability in CT and photoacoustic imaging,which could realize the integrated diagnosis and treatment scheme of multimodal imaging of tumor at the same time.W₁₈O₄₉showed phototherapeutic properties and enzyme-like activity,which has better photothermal and photodynamic therapeutic effect in NIR-II region.The phototherapy induced by W₁₈O₄₉ can improve the uptake of TRAIL to cells and induce apoptosis of tumor cells.TRAIL combined with W₁₈O₄₉-mediated phototherapy induces apoptosis of tumor cells through different mechanisms and can play a synergistic therapeutic effect.The tumor volume revealed a 4.83-fold in the phototherapy group and 10.73-fold in the TRAIL group compared with pre-treatment tumors.The tumor inhibition effect of TRAIL combined with phototherapy was more obvious in nude mice,the tumor volume was 0.56-fold compared with pre-treatment tumors.The combination therapy showed a more positive antitumor effect.To improve the sensitivity of breast cancer and other cancer cells to radiotherapy,W₁₈O₄₉containing the high atomic number of tungsten（Z=74）was used as a radiosensitizer.The number of cell clones in phototherapy combined with the radiotherapy group decreased to 17.47%.SER value increased from 1.62to 2.03,and the intensity of·OH was significantly enhanced under X-ray irradiation,which was 6.25 times higher than that in the group without X-ray irradiation,which could inhibit the metastasis of breast cancer in situ significantly.In conclusion,W₁₈O₄₉ has a good antitumor effect due to its unique physicochemical properties,and its phototherapy combined with TRAIL and radiotherapy has shown excellent antitumor properties,providing a theoretical basis for the inhibition of tumor metastasis and recurrence.