Xie Ping, Qu Ting, Tang Kexin, Huang Yuanfang, Zeng Guangfu, Yuan Huahui, Xin Qian, Zhao Yufeng, Yang Jinmei, Zeng Cheng, Wu Xian, Yang Sheng-Tao, Tang Xiaohai
Sichuan Enray Pharmaceutical Sciences Company, Chengdu 610095, China.
School of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, China.
Colloids Surf B Biointerfaces. 2025 Jun;250:114562. doi: 10.1016/j.colsurfb.2025.114562. Epub 2025 Feb 12.
Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer that lacks the expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, whose systemic treatment options are currently limited to chemotherapy. Carbon nanoparticles-Fe(II) complex (CNSI-Fe) is a promising antitumor drug that induces ferroptosis to kill tumor cells efficiently. In this study, we combined CNSI-Fe and a ferroptosis inducer sorafenib (SRF) to achieve the efficient chemotherapy of TNBC. CNSI-Fe could adsorb SRF by hydrophobic interaction and π-π stacking with a maximum adsorption capacity of 31 mg/g. During the in vitro assays, CNSI-Fe+SRF combination inhibited the cell viability of 4T1 cells much more efficiently than CNSI-Fe or SRF alone. The high Fe uptake, hydroxyl radical generation and oxidative damages verified the ferroptosis of 4T1 cells upon the CNSI-Fe+SRF treatment. During the in vivo evaluations, SRF enhanced the therapeutic effect of CNSI-Fe as indicated by the higher tumor growth inhibition rate of 67.8 % and the higher survival rate. CNSI captured SRF in tumor to give a 6 mg/kg uptake, which lowered the glutathione peroxidase 4 (GPX4) level and enhanced the hydroxyl radical production of 4T1 tumor. In addition, CNSI-Fe treatment up-regulated the genes associated with antioxidative responses, but the up-regulation was offset by SRF. CNSI-Fe+SRF group showed similar toxicity to mice as SRF alone in the biosafety evaluations. Our results collectively indicated that the combination of CNSI-Fe and SRF could efficiently treat TNBC through ferroptosis.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，缺乏雌激素受体、孕激素受体和人表皮生长因子受体2的表达，其全身治疗选择目前仅限于化疗。碳纳米颗粒 - 铁（II）复合物（CNSI-Fe）是一种有前景的抗肿瘤药物，可诱导铁死亡以有效杀死肿瘤细胞。在本研究中，我们将CNSI-Fe与铁死亡诱导剂索拉非尼（SRF）联合使用，以实现TNBC的高效化疗。CNSI-Fe可通过疏水相互作用和π-π堆积吸附SRF，最大吸附容量为31 mg/g。在体外试验中，CNSI-Fe+SRF组合比单独的CNSI-Fe或SRF更有效地抑制4T1细胞的活力。高铁摄取、羟基自由基生成和氧化损伤证实了CNSI-Fe+SRF处理后4T1细胞发生了铁死亡。在体内评估中，SRF增强了CNSI-Fe的治疗效果，肿瘤生长抑制率更高，为67.8%，生存率也更高。CNSI在肿瘤中捕获SRF，摄取量为6 mg/kg，降低了谷胱甘肽过氧化物酶4（GPX4）水平，增强了4T1肿瘤的羟基自由基产生。此外，CNSI-Fe处理上调了与抗氧化反应相关的基因，但这种上调被SRF抵消。在生物安全性评估中，CNSI-Fe+SRF组对小鼠的毒性与单独使用SRF相似。我们的结果共同表明，CNSI-Fe和SRF的组合可通过铁死亡有效治疗TNBC。
