Imaging Department, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, People's Republic of China.
Institute of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, People's Republic of China.
Int J Nanomedicine. 2024 Jun 5;19:5227-5243. doi: 10.2147/IJN.S453601. eCollection 2024.
PURPOSE: This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI). METHODS: FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed. RESULTS: The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras. CONCLUSION: We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.
目的:本研究旨在构建靶向载药纳米复合材料(FA-FePt/DDP 纳米脂质体),以探索其在卵巢癌治疗和分子磁共振成像(MMRI)中的应用潜力。
方法:通过将叶酸(FA)与聚乙二醇(PEG)包覆的铁铂纳米粒子偶联,制备 FA-FePt-NPs,并对其进行表征。然后通过薄膜超声法和高速搅拌将顺铂(DDP)包裹在 FA-FePt-NPs 中,合成 FA-PEG-FePt/DDP 纳米脂质体,分析其 MMRI 潜力、磁热效应和其他相关性能。评估 FA-FePt/DDP 纳米脂质体联合磁流体热疗(MFH)对卵巢癌的体内外治疗效果。检测 Bax 和上皮间质转化相关蛋白的表达水平。同时初步观察生物安全性。
结果:FA-FePt-NPs 的平均粒径约为 30nm,FA-FePt/DDP 纳米脂质体水合粒径约为 70nm,具有药物缓慢释放和良好的细胞特异性靶向摄取能力。在交变磁场(AMF)中,FA-FePt/DDP 纳米脂质体能够迅速达到理想的肿瘤热疗温度(42~44°C)。MRI 扫描显示,FA-FePt-NPs 和 FA-FePt/DDP 纳米脂质体均可抑制 T2 信号,表明具有良好的 MMRI 应用潜力。体外和体内实验表明,FA-FePt/DDP-NPs 在 AMF 中可通过抑制癌细胞增殖、侵袭和迁移,诱导癌细胞凋亡,有效抑制卵巢癌的生长,效果明显优于其他单一治疗方法;分子水平上,卵巢癌细胞和组织中 E-cadherin 和 Bax 蛋白明显增加,而 N-cadherin、Vimentin 和 Bcl-2 蛋白受到抑制,有效抑制了卵巢癌的恶性进展。此外,主要内脏器官未见明显的病理损伤和功能障碍。
结论:我们成功合成了 FA-FePt/DDP 纳米脂质体,并证实了其在 AMF 中良好的热化疗效果和在卵巢癌中的 MMRI 应用潜力,且无明显副作用,为卵巢癌的综合靶向治疗和诊断提供了有利策略。
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