Application Of W₁₈O₄₉ Nanospheres Loaded With Copper Ion In Cooperative Treatment Of Cancer

Malignant tumors refer to the products of organisms that have been affected by various tumorigenic factors,and local cells and tissues have lost normal regulation of their growth at the genes and expression levels,resulting in abnormal proliferation and differentiation of tissues.Due to the complexity,diversity and heterogeneity of tumors,the therapeutic potential of monotherapy such as surgical treatment,chemotherapy,and radiotherapy is severely destroyed.In recent years,research on the synergistic enhancement between multiple monotherapy has led to the rise of synergistic therapy.With the continuous breakthrough of nanotechnology,it is rapidly applied to the fields of assisted radiotherapy sensitization,chemical therapy drug loading,and target design of targeted therapy.And because a nano-material often has multiple characteristics,including controllable shape and size,excellent biocompatibility,light absorption,and easy design,it has become an excellent platform for achieving synergistic therapy.X-ray radiation therapy is one of the most important treatment methods for malignant tumors,and more than half of patients need radiotherapy.However,the radiation tolerance of hypoxic cells in a large number of solid tumors is 2-3 times that of tumor cells in an aerobic environment.The hypoxic tumor microenvironment severely reduces the sensitivity of cancer cells to X-ray radiation,which makes radiation therapy ineffective for the treatment of hypoxic solid tumors.In order to enhance the radiosensitivity of hypoxic cells in tumors and reduce the damage to surrounding nontumor tissues,on the one hand,people have developed radiosensitizers based on different principles to enhance the killing effect on tumors.On the other hand,studies have found that the warming effect caused by photothermal therapy?PTT?can accelerate the blood flow in the tumor,improve the oxygenation of the tumor,can offset the hypoxia-induced radiation resistance,and can also enhance the efficacy of radiation therapy.In this paper,the W₁₈O₄₉ nanosphere material was synthesized by hydrothermal method,and the negative-charged W₁₈O₄₉ nanosphere can adsorb positively charged copper ions to form the copper ion-loaded W₁₈O₄₉ nanospheres.SEM images,DLS,XRD and XPS studies measurements confirmed that are these nanomaterials are of W₁₈O₄₉ nature.The diameter of the copper ion-loaded W₁₈O₄₉ nanosphere is 262.6 ± 32.4 nm.The hydrodynamic diameter and surface of W₁₈O₄₉ nanospheres and the copper ion-loaded W₁₈O₄₉ nanospheres are 287.9 nm and 315.7 nm,-44.27 m V and-39.33 m V,respectively.Both W₁₈O₄₉ nanosphere materials and copper ion-loaded W₁₈O₄₉ nanospheres show strong optical absorption in NIR range from 1000 to 1400 nm and have good photothermal effects.Cell Counting Kit-8?CCK8?studies demonstrated that both W₁₈O₄₉ nanosphere materials and copper ion-loaded W₁₈O₄₉ nanospheres has good biocompatibility.After incubation with 1 mg/m L W₁₈O₄₉ nanosphere,more than 80% cell survival rate can be obtained for Hela cell line.However,for copper ion-loaded W₁₈O₄₉ nanospheres,more than 80% cell survival rate can be obtained only in the concentration range of 0.25 mg/m L,implying higher toxicity of copper ion-loaded W₁₈O₄₉ nanospheres.In vitro cell experiments also proved that W₁₈O₄₉ nanosphere materials have excellent phototherapy and X-ray radiotherapy sensitization abilities,and can achieve RT/PT dualmode synergistic treatment of human breast cancer cell line MDA-MB-231.In summary,W₁₈O₄₉ nanospheres are a radioactive sensitizer and photothermal therapeutic agent with good performance,and have the ability to achieve three levels of collaborative treatment.Including potential antiviral and hyperthermia co-treatment of the cause of cervical cancer,PTT/PDT co-treatment of tumors with near-infrared light,and RT/PT co-treatment of tumors with X-rays and light and heat.