Photothermal Effect Of CuS-BSA On Tumor Growth And Apoptosis Protein Expression In H22 Tumor-bearing Mice

Objective: To synthesis Cu S-BSA as a new photosensitizer and study its properties and photothermal effect.To study the photothermal effect of Cu S-BSA on H22 tumor bearing mice and the expression of proapoptotic protein.Method:Cu S-BSA were synthesized using bovine serum albumin(BSA)as a biological template.Characterization and the photothermal effects of Cu S-BSA were determined.Establishment of H22 tumor-bearing mouse model using male Kunming mice and 96 tumor-bearing mice were randomly divided into PBST,PBST+NIR,Cu ST,Cu ST+NIR,and Cu SV and Cu SV+NIR total six groups,16 in each group.Photothermal therapy was carried out once a week for a total of three weeks.The mice body weight and tumor volume were recorded during the experiment.Three weeks later,the mice were sacrificed.After the tissues were weighed,the tumor inhibition rate,tumor ratio,and organ index were calculated.HE staining was used to observe the tumor and liver,spleen and kidney injury.Immunohistochemistry was used to detect the expression of Cleaved Caspase-3 and Cleaved Caspase-9 proteins.The expression of Cleaved Caspase-3,Bax and Bcl-2 protein in tumor tissue was detected by Western-blot.Result:The Cu S-BSA nanomaterial is a sheet structure with a particle size of 30 nm and a Zeta potential of-29.7±2.31 m V at p H=7.It can stably exist in solvents such as water,PBS and DMEM,and has strong absorption at 980 nm peak.The heating curve shows that the photothermal effect of the Cu S-BSA solution is concentration dependent and power density dependent.The higher the concentration,the greater the power density,the more pronounced the temperature rise.In animal experiments,the tumor volume and tumor ratio were significantly lower in the Cu ST+NIR group and the Cu SV+NIR group than in the other groups and the differences compared to PBST+NIR group were statistically significant(P(27)0.05).There was no significant difference between the above two groups(P(29)0.05),and the rate of tumor inhibition were 48.8% and 41.5%,respectively.Hematoxylin-eosin staining was used to observe the tumor sections.There were large necrosis in the Cu ST+NIR group and the Cu SV+NIR group,but no necrosis was observed in other groups.There were no significant lesions in liver,spleen and kidney sections in all groups.There was no significant difference in thymus index and spleen index.Immunohistochemistry and Western-blot results showed that the expression levels of the pro-apoptotic proteins Cleaved Caspase-3 and Cleaved Caspase-9 in the Cu ST+NIR group and the Cu SV+NIR group were significantly increased,and the Bcl-2/Bax ratio was decreased,compared with the PBST+NIR group.The difference was statistically significant(P(27)0.05).Conclusion: The Cu S-BSA synthesized with bovine serum albumin as a biological template has a photothermal effect and good stability.The photothermal effect of Cu S-BSA can induce apoptosis,thereby inhibiting tumor growth and can be used for the photothermal treatment of cancer.