营养输送和代谢激活疗法治疗黑色素瘤。
Nutrient-delivery and metabolism reactivation therapy for melanoma.
机构信息
Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University Cancer Center, School of Life Sciences and Technology, Tongji University, Shanghai, P. R. China.
Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Academy for Engineering and Technology, Fudan University, Shanghai, P. R. China.
出版信息
Nat Nanotechnol. 2024 Sep;19(9):1399-1408. doi: 10.1038/s41565-024-01690-6. Epub 2024 Jun 11.
To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways.
为了满足快速增殖的需求,肿瘤细胞经历了显著的代谢改变。抑制过度激活的代谢已被证明可以对抗肿瘤生长。然而,下调的代谢途径的重新激活是否具有治疗效果仍有待探索。在这里,我们报告了一种基于营养的代谢再激活策略,可有效治疗黑色素瘤。L-酪氨酸油胺纳米胶束(MTyr-OANPs)被构建用于靶向补充酪氨酸,以重新激活黑色素瘤细胞中的黑色素生成。我们发现,使用 MTyr-OANPs 重新激活黑色素生成可显著抑制黑色素瘤细胞的增殖,主要是通过抑制糖酵解。此外,利用黑色素作为天然光热试剂进行光热治疗,我们通过用 MTyr-OANPs 和光热治疗治疗 B16F10 黑色素瘤荷瘤小鼠,证明了完全消除肿瘤。我们基于代谢激活的肿瘤治疗策略表明,特定的营养物质可以作为代谢途径的有效激活剂。