<br>超顺磁性氧化铁-Erastin-聚乙二醇纳米治疗平台：基于铁死亡的鼻咽癌综合诊断和治疗方法,Molecular Pharmaceutics

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超顺磁性氧化铁-Erastin-聚乙二醇纳米治疗平台：基于铁死亡的鼻咽癌综合诊断和治疗方法
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2024-05-12 , DOI: 10.1021/acs.molpharmaceut.3c01172
Haonan Tang ₁ , Xiao Zhou ₂ , Lijuan Liu ₁ , Ziyu Wang ₁ , Chen Wang ₁ , Ningbin Luo ₁ , Guanqiao Jin ₁

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Erastin 作为一种有效的小分子抑制剂，可以诱导肿瘤细胞铁死亡。然而，由于缺乏水溶性，其应用受到阻碍。本研究研究了通过将SPIO-PEG纳米粒子负载erastin制备的超顺磁性氧化铁（SPIO）-erastin-聚乙二醇（PEG）纳米粒子对铁死亡的影响。 SPIO-erastin-PEG纳米粒子呈方形和球形，具有良好的分散性。 SPIO-erastin-PEG 的 zeta 电位和流体动力学尺寸分别测量为 (−37.68 ± 2.706) mV 和 (45.75 ± 18.88) nm。在T ₂加权成像中，与非增强磁共振成像(MRI)相比，纳米系统显示出显着的对比度增强。 SPIO-erastin-PEG 通过增加活性氧和铁含量并促进脂质过氧化物的积累和谷胱甘肽过氧化物酶 4 的降解来诱导铁死亡。药代动力学实验显示 SPIO-erastin-PEG 溶液的半衰期为 1.25 ± 0.05 h在流通中。此外，SPIO-erastin-PEG 的显着抗肿瘤作用已在 5-8F 细胞和小鼠荷瘤肿瘤中得到证实。这些结果表明，合成的 SPIO-erastin-PEG 纳米平台可以在体外和体内诱导铁死亡效应，同时表现出良好的物理特性。该方法可能为鼻咽癌治疗诊断纳米平台提供新策略。

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Superparamagnetic Iron Oxide–Erastin–Polyethylene Glycol Nanotherapeutic Platform: A Ferroptosis-Based Approach for the Integrated Diagnosis and Treatment of Nasopharyngeal Cancer

Erastin can induce ferroptosis in tumor cells as an effective small molecule inhibitor. However, its application is hampered by a lack of water solubility. This study investigated the effects of superparamagnetic iron oxide (SPIO)–erastin–polyethylene glycol (PEG) nanoparticles prepared by loading SPIO–PEG nanoparticles with erastin on ferroptosis. SPIO–erastin–PEG nanoparticles exhibited square and spherical shapes with good dispersibility. The zeta potential and hydrodynamic size of SPIO–erastin–PEG were measured as (−37.68 ± 2.706) mV and (45.75 ± 18.88) nm, respectively. On T₂-weighted imaging, the nanosystem showed significant contrast enhancement compared to no-enhancement magnetic resonance imaging (MRI). SPIO–erastin–PEG induced ferroptosis by increasing reactive oxygen species and iron content and promoting the accumulation of lipid peroxides and the degradation of glutathione peroxidase 4. Pharmacokinetic experiments revealed a half-life of 1.25 ± 0.05 h for the SPIO–erastin–PEG solution in circulation. Moreover, significant antitumorigenic effects of SPIO–erastin–PEG have been demonstrated in 5–8F cells and mouse-bearing tumors. These results indicated that the synthesized SPIO–erastin–PEG nanoplatform could induce ferroptosis effects in vitro and in vivo while exhibiting favorable physical characteristics. This approach may provide a new strategy for theranostic nanoplatform for nasopharyngeal cancer.

更新日期：2024-05-12

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