Lysine demethylase KDM3A regulates nanophotonic hyperthermia resistance generated by 2D silicene in breast cancer.

Abstract Breast cancer (BC) is the most common malignant disease affecting women's health worldwide. The benefits from conventional therapeutic modalities are severely limited. An increasing number of promising photothermal materials have been recently developed and introduced into the therapeutic regimens of BC, but the underlying biological mechanism remains unclear. Silicon-based materials have enjoyed many popularities in the biomedical field owing to their desirable biocompatibility, biodegradability and versatility. Herein, we introduced two dimensional (2D) silicene nanosheets (SNSs) into the BC treatment and achieved profound photothermal-ablation efficacy. Importantly, this work reveals the underlying biological mechanism and regulation factors of photonic hyperthermia in BC. The RNA sequencing and immunoblot demonstrated that photothermia enhanced apoptosis in BC by activating caspase 3 and caspase 7. Importantly, knockdown of lysine demethylase KDM3A sensitized BC to photothermia epigenetically. It has been revealed that KDM3A could erase p53K372me1 and suppress the anti-cancer functions of p53, leading to the downregulation of pro-apoptotic proteins-PUMA and NOXA verified by Co-IP and ChIP-qPCR assays. Therefore, our results not only import near infrared light (NIR) induced photothermal ablation generated by SNSs-BSA into the BC treatment, but also clarify the underlying mechanism and regulation factors for further photothermal performance optimization and clinical translation.