He Chao, Yu Luodan, Ding Li, Yao Heliang, Chen Yu, Hao Yongqiang
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
State Key Lab of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.
Biomaterials. 2020 Oct;255:120181. doi: 10.1016/j.biomaterials.2020.120181. Epub 2020 Jun 10.
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.
乳腺癌（BC）是全球影响女性健康的最常见恶性疾病。传统治疗方式的疗效严重受限。最近，越来越多有前景的光热材料被开发并引入到BC的治疗方案中，但其潜在的生物学机制仍不清楚。硅基材料因其良好的生物相容性、生物可降解性和多功能性，在生物医学领域备受青睐。在此，我们将二维（2D）硅烯纳米片（SNSs）引入BC治疗，并取得了显著的光热消融效果。重要的是，这项工作揭示了BC中光子热疗的潜在生物学机制和调控因子。RNA测序和免疫印迹表明，热疗通过激活半胱天冬酶3和半胱天冬酶7增强了BC中的细胞凋亡。重要的是，赖氨酸去甲基化酶KDM3A的敲低在表观遗传上使BC对热疗敏感。研究表明，KDM3A可以消除p53K372me1并抑制p53的抗癌功能，导致通过免疫共沉淀（Co-IP）和染色质免疫沉淀定量PCR（ChIP-qPCR）分析验证的促凋亡蛋白-PUMA和NOXA的下调。因此，我们的研究结果不仅将SNSs-BSA产生的近红外光（NIR）诱导的光热消融引入到BC治疗中，还阐明了潜在机制和调控因子，以进一步优化光热性能并实现临床转化。
