Self-Assembled Spherical Cerium Oxide Inhibit Migration and Proliferation of Gastric Cancer
Gastric cancer(GC)has the fifth highest incidence rate and fourth highest mortality rate worldwide,with a highly signifi-cant risk of metastasis.Due to the difficulty in detecting early symptoms of gastric cancer and the low rate of gastric endoscopy screen-ing,most patients are already in the advanced stage at the time of diagnosis.Comprehensive treatment is the overall strategy for gastric cancer treatment,with surgery being the main focus,while chemotherapy can improve the survival rate and quality of life for patients with locally advanced unresectable or metastatic gastric cancer.The key to gastric cancer treatment is early detection,diagnosis,and appropriate treatment methods.The treatment efficacy of gastric cancer,however,is still far from satisfactory.With the 5-year survival rate for advanced gastric cancer lingering below 30％,the primary causes of cancer-related fatalities persist as tumor invasion and me-tastasis.Thus,a pressing necessity emerges for intensive exploration and advancement to enhance the survival rate and therapeutic consequences for patients grappling with gastric cancer,by discovering and employing increasingly efficacious drugs that can effective-ly stymie the proliferation and migration of gastric cancer cells.Nanotechnology,being a"disruptive technology",has demonstrated immense potential for enhancing numerous disease treatments and diagnoses.With the escalating demand for individualized and accu-rate drug therapies,there is an escalating interest in the advancement of nano particles.These nano particles have already played di-verse therapeutic roles in various diseases including chemotherapy,photodynamic therapy,radiation therapy,and immunotherapy.The continuing advancements in nanotechnology will cater to medical requirements more effectively,offering patients more personal-ized treatments and more efficient drug delivery systems.Research has found that in the field of nanomedicine,cerium oxide nanoparti-cles(CNPs)have the potential to be a highly effective treatment method for a wide range of diseases.CNPs have important prospects in the field of biomedical research due to their ability to simulate the activity of important antioxidant enzymes called superoxide anion dismutase(SOD).This unique enzyme activity is attributed to the presence of both Ce3+and Ce4+oxidation states on the surface of CNPs,which creates oxygen vacancies.These oxygen vacancies serve as binding sites for redox reactions and regulate the level of reac-tive oxygen species(ROS)within cells.ROS are normal byproducts of cellular activities such as mitochondrial metabolism and protein folding.However,when ROS levels are excessively elevated,they have the potential to induce oxidative stress in cells,ultimately leading to the aging or demise of the cell.In contrast to regular cells,cancer cells typically exhibit augmented levels of ROS and height-ened antioxidant activity in an unregulated state.Consequently,cancer cells struggle to manage additional oxidative stress and conse-quently become more vulnerable to attacks from reactive oxygen species.Therefore,augmenting intracellular ROS represents a signifi-cant avenue in the development of drugs for cancer treatment.Based on the aforementioned theory,researchers have focused on study-ing the regulation of cell proliferation by CNPs,and the reports have indicated that the size of CNPs can determine the ratio of Ce3+and Ce4+on their surface.However,ultrasmall CNPs tend to aggregate,resulting in a significant reduction in their bioactivity.Moreover,when it comes to treating gastric cancer,CNPs have not yet displayed sufficiently significant therapeutic effects,which hinder their ability to distinguish themselves among the numerous available treatment options.Therefore,it is crucial to improve the simulated en-zyme activity of CNPs.Our research team has previously enhanced the stability and aggregation of CNPs through controlled synthesis techniques,but the anti-tumor characteristics and bio-safety of CNPs still require further exploration.Therefore,this study aimed to in-vestigate the impact of spherical cerium oxide nanoparticles(Ceria-SNPs)on human gastric cancer cells(MKN-45)through the syn-thesis and characterization of controlled Ceria-SNPs.Different concentrations of Ceria-SNPs were co-cultivated with gastric cancer cells,and the cell proliferation,migration ability,and intracellular ROS levels were evaluated in both in vitro and in vivo conditions.It was discovered that a high concentration of 10.0 μg·ml-1 of Ceria-SNPs had the ability to hinder the growth and movement of gastric cancer cells,which was achieved by elevating the levels of intracellular ROS.Furthermore,the findings had been validated through ex-periments using subcutaneous tumor and abdominal metastasis models in nude mice,which confirmed the efficacy and safety of Ceria-SNPs.The results strongly suggested that by elevating intracellular ROS levels,Ceria-SNPs could effectively impede the malignant bio-logical behavior of gastric cancer.Moreover,the utilization of controllable synthesis technology provided a theoretical basis for the ap-plication of CNPs.In conclusion,it was indicated that Ceria-SNPs could effectively suppress the malignant biological behavior of gas-tric cancer by increasing intracellular ROS levels,and the application of controllable synthesis technology for cerium oxide nanoparti-cles had theoretical support.
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