Bone marrow mesenchymal stem cell-mediated ultrasmall gold nanoclusters and hNIS gene synergize radiotherapy for breast cancer.

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 131I treatment. However, the rapid outflow of 131I 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 131I concentration 9 h following 131I injection. Colony formation assay revealed that 131I, 131I combined with GSH@AuNCs could independently inhibit 39.5% and 66.4% of cell growth, respectively. Moreover, in vivo131I 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.