Zhang Lu, Zheng BenChao, Guo Rui, Miao Ying, Li Biao
Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai JiaoTong University, P. R. China.
J Mater Chem B. 2021 Mar 28;9(12):2866-2876. doi: 10.1039/d1tb00186h. Epub 2021 Mar 15.
The human sodium iodide symporter (hNIS) can be linked to the downstream of radiation-sensitive early growth response protein1 (Egr1) promoter, and activated by the Egr1 following I treatment. However, the rapid outflow of I restricted the radiotherapy effect. To overcome this barrier, ultrasmall gold nanoclusters (usAuNCs) were used to enhance the radiotherapy efficacy of Egr1-hNIS for its radiation sensitization. In this work, we prepared "cell bomb" BMSCs carrying both GSH@AuNCs and Egr1-hNIS. We found that the "cell bomb" can target TNBC tumor and reach a maximum I concentration 9 h following I injection. Colony formation assay revealed that I, I combined with GSH@AuNCs could independently inhibit 39.5% and 66.4% of cell growth, respectively. Moreover, in vivoI therapy further demonstrated that the growth of triple negative breast cancer (TNBC) was controlled by BMSC-Egr1-hNIS + AuNCs group, with relative volume inhibition percentages of 56.16% (compared with the control group) and 36.20% (compared with the BMSC-Egr1-hNIS group), respectively. To summarize, we successfully prepared BMSC-Egr1-hNIS carrying GSH@AuNCs to target TNBC which could synergistically improve the efficacy of hNIS gene therapy.
人钠碘同向转运体（hNIS）可与辐射敏感的早期生长反应蛋白1（Egr1）启动子下游相连，并在碘治疗后被Egr1激活。然而，碘的快速流出限制了放射治疗效果。为克服这一障碍，使用超小金纳米团簇（usAuNCs）来增强Egr1-hNIS的放射治疗疗效及其辐射增敏作用。在这项工作中，我们制备了携带谷胱甘肽@金纳米团簇（GSH@AuNCs）和Egr1-hNIS的“细胞炸弹”骨髓间充质干细胞（BMSCs）。我们发现“细胞炸弹”可靶向三阴性乳腺癌（TNBC）肿瘤，并在注射碘后9小时达到最大碘浓度。集落形成试验表明，碘、碘与GSH@AuNCs联合使用可分别独立抑制39.5%和66.4%的细胞生长。此外，体内碘治疗进一步证明，三阴性乳腺癌（TNBC）的生长受到BMSC-Egr1-hNIS + AuNCs组的控制，相对体积抑制率分别为56.16%（与对照组相比）和36.20%（与BMSC-Egr1-hNIS组相比）。总之，我们成功制备了携带GSH@AuNCs的BMSC-Egr1-hNIS以靶向TNBC，其可协同提高hNIS基因治疗的疗效。
