Cui Junming, Cai Xinxi, Qian Rui, Wu Lin, Qi Xueyong, Cao Jin, Shen Song
Department of Pharmacy, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
College of Pharmaceutical Sciences, Jiangsu University, Zhenjiang 212013, China.
Pharmaceutics. 2024 May 9;16(5):639. doi: 10.3390/pharmaceutics16050639.
Artemisinin has an endoperoxide bridge structure, which can be cleaved by ferrous ions to generate various carbonyl radicals in an oxygen-independent manner, highlighting its potential for treating hypoxic tumors. In our study, we fabricated Tween 80 micelles loaded with FeO nanoparticles and artemisinin for cancer therapy. The synthesized FeO nanoparticles and drug-loaded micelles have particle sizes of about 5 nm and 80 nm, respectively, both exhibiting excellent dispersibility and stability. After uptake by MCF-7 cells, drug-loaded micelles release Fe and ART into the cytoplasm, effectively inducing the generation of reactive oxygen species (ROS) in hypoxic conditions, thereby enhancing toxicity against cancer cells. In vitro and in vivo studies have demonstrated that ART and FeO nanoparticles are encapsulated in Tween 80 to form micelles, which effectively prevent premature release during circulation in the body. Although free ART and FeO nanoparticles can inhibit tumor growth, TW80-FeO-ART micelles demonstrate a more pronounced inhibitory effect, with a tumor suppression rate of up to 85%. A novel strategy based on artemisinin and ferroptosis is thus offered, holding a favorable prospect for hypoxic cancer therapy.
青蒿素具有内过氧化物桥结构，其可被亚铁离子裂解，以不依赖氧气的方式产生各种羰基自由基，这突出了其治疗缺氧肿瘤的潜力。在我们的研究中，我们制备了负载FeO纳米颗粒和青蒿素的吐温80胶束用于癌症治疗。合成的FeO纳米颗粒和载药胶束的粒径分别约为5nm和80nm，均表现出优异的分散性和稳定性。被MCF-7细胞摄取后，载药胶束将铁和青蒿素释放到细胞质中，在缺氧条件下有效诱导活性氧（ROS）的产生，从而增强对癌细胞的毒性。体外和体内研究表明，青蒿素和FeO纳米颗粒被包裹在吐温80中形成胶束，这有效地防止了其在体内循环期间的过早释放。尽管游离青蒿素和FeO纳米颗粒可以抑制肿瘤生长，但TW80-FeO-ART胶束表现出更显著的抑制作用，肿瘤抑制率高达85%。因此，提供了一种基于青蒿素和铁死亡的新策略，为缺氧癌症治疗带来了良好的前景。
