摘要
乳腺癌骨转移干扰骨的正常代谢,成骨分化是骨代谢的重要过程,通过促进成骨分化,可有效改善骨转移局部环境,提高治疗效果。因此,开发抑制乳腺癌并调节成骨分化的双功能药物,可能为乳腺癌骨转移的治疗提供新策略。雷公藤是具有抗肿瘤活性的天然药物,但其毒性限制了其应用及相关药物开发。本研究制备雷公藤来源的碳点(Tripterygium wilfordii carbon dots, T-CDs),通过光谱分析、动态光散射及透射电子显微镜对其表征,并在体外评估其抗乳腺癌及成骨调控效应。结果显示, T-CDs呈近球形,晶格间距0.20 nm,平均粒径5.38 nm, ζ电位-8.46 mV,表面富含-OH、C=O、C=C等官能团,并在280 nm处显示紫外吸收;一方面, T-CDs可通过破坏乳腺癌细胞氧化还原稳态诱导乳腺癌细胞铁死亡,同时触发免疫原性细胞死亡;另一方面, T-CDs可通过调节乳腺癌细胞因子分泌水平,促进成骨细胞的分化,有望用于治疗乳腺癌及其骨转移。
Breast cancer bone metastasis disrupts bone metabolism,enhancing osteogenic differentiation can improve the metastatic microenvironment and treatment outcomes.Thus,developing agents that inhibit breast cancer and promote osteogenesis may offer new strategies.Tripterygium wilfordii possesses antitumor and bone-regulating properties,but its toxicity limits clinical application.Here,a carbon dot was synthesized from Tripterygium wilfordii(Tripterygium wilfordii carbon dots,T-CDs)and characterized by spectral analysis,dynamic light scattering,and transmission electron microscopy.T-CDs exhibited a near-spherical morphology with a lattice spacing of 0.20 nm,an average size of 5.38 nm,and aζpotential of−8.46 mV.The surface was rich in-OH,C=O,and C=C groups,with ultraviolet absorption at 280 nm.T-CDs disrupted redox homeostasis in breast cancer cells,inducing ferroptosis and immunogenic cell death.Moreover,T-CDs modulated cytokine secretion and promoted osteogenic differentiation,offering potential for the treatment of breast cancer and its bone metastasis.
作者
韩东立
崔君祎
李肖
陈子超
王晓婷
刘辉
郑昊
张振
HAN Dong-li;CUI Jun-yi;LI Xiao;CHEN Zi-chao;WANG Xiao-ting;LIU Hui;ZHENG Hao;ZHANG Zhen(Innovation Institute of Chinese Medicine and Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Linyi People's Hospital,Linyi 276000,China;School of Pharmacy and Food Engineering,Liaocheng University,Liaocheng 252000,China)
出处
《药学学报》
北大核心
2025年第11期3426-3434,共9页
Acta Pharmaceutica Sinica
基金
国家自然科学基金项目(21775061)
泰山学者青年专家计划项目(tsqn202211136)
山东省中医药科技项目(M-2023182)
山东大学“新高校20条”资助项目(202228085)
山东中医药大学青年创新团队支持计划项目(22202401)。
关键词
碳点
雷公藤
乳腺癌
铁死亡
成骨分化
骨转移
carbon dot
Tripterygium wilfordii
breast cancer
ferroptosis
osteogenic differentiation
bone metastasis
