Guo Ting, Zhu Yinxing, Yue Miao, Wang Fujin, Li Zhifeng, Lin Mei
Institute of Clinical Medicine, Taizhou People's Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, China.
Clinical Laboratory, Taizhou People's Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, China.
Front Oncol. 2022 Mar 25;12:811783. doi: 10.3389/fonc.2022.811783. eCollection 2022.
Globally, ovarian cancer is one of the most common gynecological malignant tumors, and the overall curative effect has been unsatisfactory for years. Exploring and investigating novel therapeutic strategy for ovarian cancer are an imperative need.
Using manganese zinc ferrite nanoparticles (PEG-MZF-NPs) as gene transferring vector and drug delivery carrier, a new combinatorial regimen for the target treatment of ovarian cancer by integrating CD44-shRNA, DDP (cisplatin) and magnetic fluid hyperthermia (MFH) together was designed and investigated and in this study.
PEG-MZF-NPs/DDP/CD44-shRNA nanoliposomes were successfully prepared, and TEM detection indicated that they were 15-20 nm in diameter, with good magnetothermal effect in AMF, similar to the previously prepared PEG-MZF-NPs. Under the action of AMF, PEG-MZF-NPs/shRNA/DDP nanoliposomes effectively inhibited ovarian tumors' growth, restrained the cancer cells' proliferation and invasion, and promoted cell apoptosis. VEGF, survivin, BCL-2, and BCL-xl proteins significantly decreased, while caspase-3 and caspase-9 proteins markedly increased both and , far better than any of the individual therapies did. Moreover, no significant effects were found on bone marrow hematopoiesis and liver and kidney function of nude mice intervened by the combinatorial therapeutic regimen.
In the present study, we developed PEG-MZF-NPs/DDP/CD44-shRNA magnetic nanoliposomes and inaugurated an integrated therapy through the synergistic effect of MFH, gene therapy, and chemotherapy, and it shows a satisfactory therapeutic effect on ovarian cancer and , much better than any single treatment regimen did, with no significant side effects. This study provides a new promising method for ovarian cancer treatment.
在全球范围内，卵巢癌是最常见的妇科恶性肿瘤之一，多年来总体疗效一直不尽人意。探索和研究卵巢癌的新型治疗策略迫在眉睫。
以锰锌铁氧体纳米颗粒（PEG-MZF-NPs）作为基因传递载体和药物递送载体，设计并研究了一种将CD44-shRNA、顺铂（DDP）和磁流体热疗（MFH）整合在一起用于卵巢癌靶向治疗的新联合方案。
成功制备了PEG-MZF-NPs/DDP/CD44-shRNA纳米脂质体，透射电镜检测表明其直径为15-20nm，在交变磁场中具有良好的磁热效应，与先前制备的PEG-MZF-NPs相似。在交变磁场作用下，PEG-MZF-NPs/shRNA/DDP纳米脂质体有效抑制卵巢肿瘤生长，抑制癌细胞增殖和侵袭，并促进细胞凋亡。VEGF、survivin、BCL-2和BCL-xl蛋白显著降低，而caspase-3和caspase-9蛋白显著增加，两者均远优于任何单一疗法。此外，联合治疗方案对裸鼠的骨髓造血及肝肾功能无明显影响。
在本研究中，我们开发了PEG-MZF-NPs/DDP/CD44-shRNA磁性纳米脂质体，并通过磁流体热疗、基因治疗和化疗的协同作用开创了一种综合治疗方法，其对卵巢癌显示出令人满意的治疗效果，远优于任何单一治疗方案，且无明显副作用。本研究为卵巢癌治疗提供了一种新的有前景的方法。
