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载有阿霉素的磁脂质体在大鼠C6胶质瘤综合化疗与热疗中的应用

Applications of magnetoliposomes with encapsulated doxorubicin for integrated chemotherapy and hyperthermia of rat C6 glioma.

作者信息

Babincová Natália, Sourivong Paul, Babinec Peter, Bergemann Christian, Babincová Melánia, Durdík Štefan

机构信息

Department of Dermatovenerology, Faculty of Medicine, Comenius University, Mickiewiczova 13, 813 69 Bratislava, Slovakia.

Oklahoma Cancer Specialists and Research Institute, 12697 East 51st Street South, Tulsa, OK 74146, USA.

出版信息

Z Naturforsch C J Biosci. 2018 Jul 26;73(7-8):265-271. doi: 10.1515/znc-2017-0110.

DOI:10.1515/znc-2017-0110
PMID:29894307
Abstract

There is substantial evidence regarding enhanced antitumor cytotoxicity of selected chemotherapeutic agents by appropriate heat exposure (40-44°C). Based upon these results, the integration of hyperthermia as an additional treatment modality given simultaneously with systemic chemotherapy is currently of considerable interest. Hyperthermia can be induced by alternating magnetic field and magnetic nanoparticles. Thus, we have used thermosensitive magnetoliposomes that contained superparamagnetic iron oxide nanoparticles and doxorubicin for in vitro and in vivo therapy of rat glioma C6. The results showed that magnetoliposomes can be specifically heated to 43°C (phase transition temperature of a used lipid composition) in a few minutes, and during this, the encapsulated doxorubicin is released in a controllable manner. The in vitro experiments showed that the cell viability decreased to 79.2% after heat treatment alone and to 47.4% for doxorubicin-loaded magnetoliposomes without application of alternating magnetic field, while the combined treatment resulted in 17.3% cell viability. Also, in vivo results demonstrated that magnetic drug targeting has a strong antiglioma effect with a tumor volume growth inhibition and complete regression. Such targeted delivery and controlled release of anticancer agents would provide clinical advantages compared with currently available methods.

摘要

有大量证据表明,适当的热暴露(40-44°C)可增强某些化疗药物的抗肿瘤细胞毒性。基于这些结果,将热疗作为一种与全身化疗同时进行的额外治疗方式目前备受关注。交变磁场和磁性纳米颗粒可诱导产生热疗。因此,我们使用了含有超顺磁性氧化铁纳米颗粒和阿霉素的热敏磁脂质体,用于大鼠胶质瘤C6的体外和体内治疗。结果表明,磁脂质体可在几分钟内特异性加热至43°C(所用脂质组合物的相变温度),在此过程中,包封的阿霉素以可控方式释放。体外实验表明,单独热处理后细胞活力降至79.2%,未施加交变磁场的载阿霉素磁脂质体处理后细胞活力降至47.4%,而联合处理后细胞活力为17.3%。此外,体内结果表明,磁性药物靶向具有很强的抗胶质瘤作用,可抑制肿瘤体积生长并使其完全消退。与现有方法相比,这种抗癌药物的靶向递送和控释将具有临床优势。

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