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

Abstract

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.