■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)中的潜力。
■通过将叶酸(FA)与聚乙二醇(PEG)包覆的铂铁纳米颗粒偶联来制备FA-FePt-NP,并进行表征。然后将顺铂(DDP)封装在FA-FePt-NP中,通过薄膜超声法和高速搅拌合成FA-PEG-FePt/DDP纳米脂质体,其中MMRI的潜力,磁热效应,并对其他涉及的绩效进行了分析。评估了FA-FePt/DDP纳米脂质体联合磁流体热疗(MFH)对卵巢癌的体外和体内治疗作用。检测Bax和上皮间质转化相关蛋白的表达水平。还初步观察到了生物安全性。
■FA-FePt-NP的平均直径约为30nm,FA-FePt/DDP纳米脂质体的水合粒径约为70nm,具有药物缓慢释放和良好的细胞特异性靶向摄取。在交变磁场(AMF)中,FA-FePt/DDP纳米脂质体可迅速达到理想的肿瘤热疗温度(42~44℃)。MRI扫描显示FA-FePt-NPs和FA-FePt/DDP纳米脂质体均能抑制T2信号,表明MMRI具有良好的潜力。体内外实验表明,AMF中的FA-FePt/DDP-NPs可以通过抑制癌细胞增殖来有效抑制卵巢癌的生长,入侵,和移民,诱导癌细胞凋亡,比其他单独疗法好得多;在分子上,E-cadherin和Bax蛋白在卵巢癌细胞和组织中显著升高,而N-钙粘蛋白,Vimentin,Bcl-2蛋白被抑制,有效抑制卵巢癌的恶性进展。此外,在主要脏器中未观察到明显的病理损伤和功能障碍。
■我们成功合成了FA-FePt/DDP纳米脂质体,并证实了它们在AMF和MMRI对卵巢癌的潜力中具有良好的热化疗效果,没有明显的副作用,为卵巢癌的综合靶向治疗和诊断提供了有利的策略。
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.