NK cells-based cancer therapy combined with chemotherapeutic drugs for the treatment of tumors can enhance the immunosensitivity of NK cells, increase the expression of NK cell receptors, and eventually boost the killing effect of NK cells on cancer cells. Selenium (Se) with different chemical structures can be metabolized into selenoproteins to regulate tumor and immune cells’ fate and functions. Herein, we found that, functionalized Se nanoparticles (SeNPs) combining with metformin (met) could amply the immunotherapeutic effects of NK92 cells against osteosarcoma cancer. The results revealed that TW80-SeNPs combined with met had the optimum performance on NK92 cells for HepG2 cells, owing to the increased ROS in HepG2 cells and the augmented expression of cell surface receptor proteins ULBP-3/4, PD-L1, MICA, and NK92 cell surface receptor proteins PD-1 and FasL. Additionally, TW80-SeNPs were gradually metabolized into selenoproteins (Gpx4 and TR1) into human osteosarcoma MG63 cells to reinforce the anticancer effect of NK92 cells by regulating the redox balance in the tumor microenvironment. This study provides a therapeutic approach in treating cancer itself or diabetes coupled with cancer. Moreover, it provides a multidrug strategy to improve immune cell function in practical applications, especially for synergistic immunotherapy of osteosarcoma.

中文翻译：

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高活性硒纳米药物联合二甲双胍对骨肉瘤治疗的NK细胞达到协同增敏作用

以NK细胞为基础的癌症治疗联合化疗药物治疗肿瘤可以增强NK细胞的免疫敏感性，增加NK细胞受体的表达，最终增强NK细胞对癌细胞的杀伤作用。具有不同化学结构的硒（Se）可以代谢成硒蛋白，从而调节肿瘤和免疫细胞的命运和功能。在此，我们发现功能化硒纳米颗粒（SeNPs）与二甲双胍（met）结合可以增强NK92细胞对骨肉瘤的免疫治疗作用。结果表明，TW80-SeNPs联合met对HepG2细胞的NK92细胞具有最佳性能，这是由于HepG2细胞中活性氧的增加和细胞表面受体蛋白ULBP-3/4、PD-L1、MICA、和 NK92 细胞表面受体蛋白 PD-1 和 FasL。此外，TW80-SeNPs逐渐代谢成硒蛋白（Gpx4和TR1）进入人骨肉瘤MG63细胞，通过调节肿瘤微环境中的氧化还原平衡来增强NK92细胞的抗癌作用。这项研究提供了一种治疗癌症本身或糖尿病合并癌症的治疗方法。此外，它在实际应用中提供了一种多药策略来改善免疫细胞功能，特别是对于骨肉瘤的协同免疫治疗。这项研究提供了一种治疗癌症本身或糖尿病合并癌症的治疗方法。此外，它在实际应用中提供了一种多药策略来改善免疫细胞功能，特别是对于骨肉瘤的协同免疫治疗。这项研究提供了一种治疗癌症本身或糖尿病合并癌症的治疗方法。此外，它在实际应用中提供了一种多药策略来改善免疫细胞功能，特别是对于骨肉瘤的协同免疫治疗。