Liang Zicheng, Fang Xiayi, Zhang Zhen, Tao Mengjuan, Gong Wenling, Jian Huiyin, Tan Xiaoning, Zeng Puhua
Graduate school, Hunan University of Chinese Medicine, Changsha 410208, PR China.
Department of Oncology, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha 410006, PR China.
Cell Signal. 2025 Oct;134:111928. doi: 10.1016/j.cellsig.2025.111928. Epub 2025 Jun 6.
To isolate exosome-like nanovesicles from Salvia chinensis Benth (SCENs), and expire the mechanisms SCENs induce ferroptosis in hepatocellular carcinoma (HCC) in vivo and in vitro, thereby offering a novel therapeutic option for HCC. SCENs were isolated from fresh Salvia chinensis Benth by ultra-centrifugation and gradient sucrose solution purification methods. The physicochemical properties of SCENs were characterized through NTA, TEM and LC-MS/MS. RNA-Seq was used to evaluate SCENs in regulating mRNA expression in vitro. The be uptake of SCENs by HepG2, MHCC97H, HuH-7, and HL-7702 cells was assessed by DIO fluorescent probes. The anti-proliferative, anti-migratory, anti-invasive, and pro-apoptotic effects of SCENs on HCC were evaluated in vitro. Experiments were conducted in vitro and vivo to investigate the role of SCENs in inducing ferroptosis in HCC and determine which mechanism is associated. The biosafety of SCENs was assessed in vitro and vivo. SCENs were uptake by HepG2, MHCC97H, and HuH-7 cells. SCENs exhibited anti-proliferative, anti-migratory, anti-invasive, pro-apoptotic, and ferroptosis-inducing effects on HCC. Both in vitro experiments and HCC models demonstrated that SCENs-induced ferroptosis in HCC was associated with the AMPK/Nrf2/xCT axis. Additionally, SCENs displayed excellent biosafety profiles in vitro and vivo. SCENs demonstrate significant anti-HCC effects, excellent biosafety, and accessibility, showcasing their potential in the development and application of anti-HCC nanotherapy.
从丹参中分离出类外泌体纳米囊泡（SCENs），并探究SCENs在体内外诱导肝癌（HCC）细胞发生铁死亡的机制，从而为肝癌提供一种新的治疗选择。通过超速离心和梯度蔗糖溶液纯化法从新鲜丹参中分离出SCENs。通过纳米颗粒跟踪分析（NTA）、透射电子显微镜（TEM）和液相色谱-串联质谱（LC-MS/MS）对SCENs的理化性质进行表征。利用RNA测序（RNA-Seq）评估SCENs在体外对mRNA表达的调控作用。用二碘荧光探针评估HepG2、MHCC97H、HuH-7和HL-7702细胞对SCENs的摄取情况。在体外评估SCENs对肝癌细胞的抗增殖、抗迁移、抗侵袭和促凋亡作用。进行体内外实验以研究SCENs在诱导肝癌细胞铁死亡中的作用，并确定其相关机制。在体内外评估SCENs的生物安全性。HepG2、MHCC97H和HuH-7细胞摄取了SCENs。SCENs对肝癌细胞具有抗增殖、抗迁移、抗侵袭、促凋亡和诱导铁死亡的作用。体外实验和肝癌模型均表明，SCENs诱导肝癌细胞铁死亡与AMPK/Nrf2/xCT轴有关。此外，SCENs在体内外均表现出良好的生物安全性。SCENs具有显著的抗肝癌作用、良好的生物安全性和可及性，展现了其在抗肝癌纳米治疗开发与应用中的潜力。
