硒化亚铜纳米颗粒通过化学动力疗法诱导胃癌细胞铁死亡的研究

Cu_(2)Se nanoparticles induce ferroptosis on gastric cancer cells through chemo-dynamic therapy

目的探讨硒化亚铜(Cu_(2)Se)纳米的制备、物化表征及其对胃癌的抗肿瘤效应。方法采用透射电镜,水合粒径分析,Zeta电位分析及紫外吸收光谱分析方法分析Cu_(2)Se纳米的形貌、粒径大小及类芬顿性能,同时采用激光共聚焦、细胞毒性(CCK-8)、Transwell实验评估该纳米的体外抗肿瘤作用效应毒性,最后构建单侧皮下荷瘤模型探究Cu_(2)Se纳米的体内抗肿瘤作用。结果制备的Cu_(2)Se纳米为100 nm左右的类圆形中空结构,可催化过氧化氢生成单线氧。激光共聚焦实验表明Cu_(2)Se可以促进胃癌细胞活性氧生成,诱导铁死亡发生;CCK-8实验表明,Cu_(2)Se纳米对胃癌细胞具有浓度依赖性抑制增殖作用;Transwell实验表明,Cu_(2)Se纳米能抑制胃癌细胞的侵袭迁移能力;裸鼠单侧皮下荷瘤模型表明Cu_(2)Se纳米能安全高效抑制肿瘤增殖。结论Cu_(2)Se纳米具有良好的类芬顿效能,可诱导胃癌铁死亡发生,具备良好的体内外抑制抗肿瘤效应,是胃癌治疗的一种潜在新方法。

Objective To investigate the preparation,physicochemical characterization of cuprous selenide nanoparticles(Cu_(2)Se NPs),and their antitumor effect on gastric cancer(GC).Methods The morphology,size and Fenton-like properties of Cu_(2)Se NPs were analyzed by transmission electron microscopy(TEM),size distributions,Zeta potential and UV absorption spectroscopy.Meanwhile,confocal laser scanning microscopy(CLSM),Cell Counting Kit-8(CCK-8)and Transwell experiments were used to evaluate the in vitro antitumor effect of Cu_(2)Se NPs.Finally,subcutaneous tumor-bearing mice were constructed to explore the in vivo antitumor effect of Cu_(2)Se NPs.Results Our as-designed Cu_(2)Se NPs showed quasi-circular hollow structures with~100 nm,which could catalyze the generation of singlet oxygen from hydrogen peroxide.CLSM results showed that Cu_(2)Se could help generate reactive oxygen species(ROS)and induce ferroptosis in GC cells.CCK-8 results showed that Cu_(2)Se had a concentration-dependent inhibitory effect on the proliferation of GC ells.Transwell experiments showed that Cu_(2)Se could suppress the migration and invasion capacities of GC cells.Tumor-bearing nude mice demonstrated that Cu_(2)Se could efficiently reduce proliferation of GC with high safety.Conclusion Cu_(2)Se NPs have good Fenton-like efficacy,which could induce ferroptosis,and showed good inhibitory effects on GC in vitro and in vivo.Therefore,our research serves a potential novel method for GC treatment.