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

Abstract 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.