Regulation of ID4 In Vivo for Efficient Magnetothermal Therapy of Breast Cancer

Magnetic nanoparticles (MNPs) mediated magnetothermal therapy (MTT) has been proven as a promising modality for tumor treatment. However, the low therapeutic efficacy presents a major obstacle to its mass adoption. The Authors proposed to increase the therapeutic efficacy of MTT through the manipulation of magnetothermal-related gene expression. ID4, a member of inhibitors of differentiation (ID) protein family, is identified to be downregulated in intracellular MTT (in-MTT)-treated MCF-7 breast cancer cells according to the whole transcriptome sequencing. Interestingly, this occurrence is not observed in the exogenous MTT-treated cells. More importantly, ID4-silenced tumor cells show significantly decreased cell viability after in-MTT, whereas ID4-overexpressed cells exhibit more resistance to the MTT. This effect is also observed in other malignant breast cells derived from the human mammary gland. Furthermore, ID4 siRNA-loaded superparamagnetic iron oxide nanoparticles are developed and delivered them to breast cancer xenografted nude mice. It is found that the synergistic combination of ID4 gene silencing and in-MTT greatly inhibited the tumor growth and the efficacy of tumor volume inhibition is > 98%. This study, for the first time, provides the possibility of the sensitization of breast cancer cells for efficient MTT via molecular manipulation of cell signaling.