使用mP6/Rg3胶束的CD44靶向治疗可抑制口腔癌干细胞的增殖和迁移。
CD44-targeted therapy using mP6/Rg3 micelles inhibits oral cancer stem cell proliferation and migration.
作者信息
Cai Sijia, Chen Yuwen, Chen Changyu, Liu Ming
机构信息
Department of Orthodontics, School of Stomatology, China Medical University, Shenyang, Liaoning, 110002, P.R. China.
Department of Ultrasound, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, P.R. China.
出版信息
Cell Biol Toxicol. 2025 Aug 1;41(1):122. doi: 10.1007/s10565-025-10070-2.
BACKGROUND
This study investigates how mP6/Rg3 micelles modulate ABCB1 expression to induce ferroptosis in oral cancer stem cells (CSC) and enhance oral cancer outcomes.
METHODS
Micelles targeting CD44 peptide P6 were prepared and characterized using TEM and immunofluorescence. Biocompatibility was evaluated through LIVE/DEAD staining and CCK-8 assays. Impact on oral cancer CSC was assessed through in vitro and OSCC mouse model studies using transcriptomic profiling, proteomic analysis, and metabolomic screening.
RESULTS
mP6/Rg3 micelles exhibited good biodegradability, inhibiting CSC proliferation and migration. Integrated multi-omics analysis highlighted ABCB1 as a pivotal modulator in OSCC. Functional assays in cell and animal models validated micelles promote ferroptosis in CSC by inhibiting ABCB1, improving OSCC pathology.
CONCLUSIONS
Targeting ABCB1 with mP6/Rg3 micelles and regulating CD44 presents a promising approach to suppress oral cancer progression by impacting CSC and tumor metabolic pathways. This study offers crucial molecular insights for new therapeutic strategies in oral cancer treatment.
背景
本研究探讨mP6/Rg3胶束如何调节ABCB1表达以诱导口腔癌干细胞（CSC）铁死亡并改善口腔癌预后。
方法
制备靶向CD44肽P6的胶束，并通过透射电子显微镜（TEM）和免疫荧光进行表征。通过活/死染色和CCK-8试验评估生物相容性。通过使用转录组分析、蛋白质组分析和代谢组筛选的体外和口腔鳞状细胞癌（OSCC）小鼠模型研究评估对口腔癌CSC的影响。
结果
mP6/Rg3胶束具有良好的生物降解性，可抑制CSC增殖和迁移。综合多组学分析突出了ABCB1作为OSCC中的关键调节因子。细胞和动物模型中的功能试验证实，胶束通过抑制ABCB1促进CSC中的铁死亡，改善OSCC病理状况。
结论
用mP6/Rg3胶束靶向ABCB1并调节CD44是一种通过影响CSC和肿瘤代谢途径抑制口腔癌进展的有前景的方法。本研究为口腔癌治疗的新治疗策略提供了关键的分子见解。
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