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叶酸靶向温敏磁脂体的制备及其体内外抗肿瘤作用。

Preparation of Folic Acid-Targeted Temperature-Sensitive Magnetoliposomes and their Antitumor Effects In Vitro and In Vivo.

机构信息

School of Medicine, Southeast University, Nanjing, 210009, People's Republic of China.

Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi, 214002, People's Republic of China.

出版信息

Target Oncol. 2018 Aug;13(4):481-494. doi: 10.1007/s11523-018-0577-y.

DOI:10.1007/s11523-018-0577-y
PMID:29992403
Abstract

BACKGROUND

Ovarian cancer is a common gynecologic malignancy with poor prognosis, requiring innovative new therapeutic strategies. Temperature-controlled drug delivery to cancer cells represents a novel, promising, targeted treatment approach.

OBJECTIVE

We prepared folate receptor-targeted thermosensitive liposomes wrapped with the HSP90 inhibitor 17-AAG and superparamagnetic material (17-AAG/MTSLs-FA), and tested the efficacy of these targeted magnetoliposomes in vitro and in vivo.

METHODS

Magnetic thermosensitive liposomes wrapped with 17-AAG were coprecipitated with FeO magnetic nanoparticles and prepared by a rotary evaporation method. Experiments were conducted with SKOV3 human ovarian cancer cells and MCF7 human breast carcinoma cells to evaluate the anti-tumor effects.

RESULTS

17-AAG/MTSLs-FA prepared in this study met the basic requirements for therapeutic application. The preparation method is relatively simple and the raw materials are readily available. The product exhibited strong magnetism, high encapsulation efficiencies, and satisfactory performance. The liposomes combined with hyperthermia significantly inhibited the proliferation of SKOV3 cells and induced apoptosis. Experiments using a mouse subcutaneous model as well as an ascites tumor xenograft model indicated that 17-AAG/MTSLs-FA was stable in vivo and effectively targeted tumor tissues expressing the folate receptor.

CONCLUSIONS

Folic acid-conjugated 17-AAG magnetic thermosensitive liposomes in combination with an alternating magnetic field for heating can achieve a synergistic anti-tumor effect of chemotherapy and heat treatment, potentially offering a new method for ovarian cancer treatment.

摘要

背景

卵巢癌是一种常见的妇科恶性肿瘤,预后不良,需要创新的治疗策略。将药物递送到癌细胞中并控温是一种新颖、有前景的靶向治疗方法。

目的

我们制备了叶酸受体靶向的热敏感脂质体,包裹热休克蛋白 90(HSP90)抑制剂 17-AAG 和超顺磁材料(17-AAG/MTSLs-FA),并测试了这些靶向磁脂质体在体外和体内的疗效。

方法

采用共沉淀法将 17-AAG 包裹在磁性热敏脂质体中,并通过旋转蒸发法制备。实验采用 SKOV3 人卵巢癌细胞和 MCF7 人乳腺癌细胞进行,评估抗肿瘤效果。

结果

本研究制备的 17-AAG/MTSLs-FA 基本符合治疗应用的要求。该制备方法相对简单,原料易得。所制备的产品具有较强的磁性、较高的包封率和满意的性能。脂质体与热疗联合使用可显著抑制 SKOV3 细胞的增殖并诱导细胞凋亡。小鼠皮下模型和腹水肿瘤异种移植模型实验表明,17-AAG/MTSLs-FA 在体内稳定,能有效靶向表达叶酸受体的肿瘤组织。

结论

叶酸偶联的 17-AAG 磁性热敏脂质体与交变磁场加热相结合,可实现化疗和热疗的协同抗肿瘤作用,为卵巢癌的治疗提供了一种新方法。

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