文献：

Novel Multifunctional Magnetic Nanoparticles： AnEffi cient Theranostic Platform for Magnetic Resonance Imaging and Targeted Therapy of Cervical Cancer

文献链接：

https://www.semanticscholar.org/paper/Novel-Multifunctional-Magnetic-Nanoparticles%EF%BC%9AAn-for-Yao-Li/f9903de229946c90fee32e056e1ac124dea8bca1

作者：

Shu Yao，Li Li，Chang Liu，Ziying Wang，Hong Liu，Xuantao Su，Zaijun Lu，Zhiping Liu，Xu Qiao ，Li Song ，Ran Chu ，Jinyu Meng，Xiyu Pan ，Kun song，Beihua Kong

相关产品：

KHMDS/环氧乙烷/丙交酯

原文摘要：Background: The high incidence and mortality rates of cervical cancer pose a serious threat to women's health. Traditional chemotherapy has inevitable drawbacks of nonspecifi c tumor targeting, high toxicity, and poor therapeutic effi ciency. In order to overcome these shortcomings, a novel multifunctional magnetic nanoparticles drug delivery system with tumor targeting and magnetic resonance imaging was developed to achieve precise diagnosis and targeted tumor killing effects.

Methods: Transmission electron microscopy, dynamic light scatting and ultraviolet methods were used to characterize the nanoparticles in vitro. Cell function tests were performed by scratch, transwell and fl ow cytometry assays. MTT was used to detect the toxicity of the nanoparticles. The motion trajectory, drug release and uptake studies were carried out in vitro. The in vivo pharmacokinetic and drug distribution studies were verifi ed by high performance liquid chromatography methods. Attenuation of the MRI signal by the nanoparticles and their enhanced antitumor effi ciency were examined in vivo in mouse cervical cancer models. Sequencing and proteomics were used to detect the key antitumor molecules of the

nanoparticles.

Results: Multifunctional magnetic nanoparticles coated with ferric oxide nanoparticles and doxorubicin hydrochloride (DOX-Fe3O4 -PEG-PLA-NPs) was prepared successfully. No toxicity was detected of PEGPLA-NP, however, the tumor killing effect was enhanced under the alternating magnetic fi eld signifi cantly. The drug-release study showed that the cumulative release rates of NP groups were much less than free DOX group, while the drug release rate increased under acidic condition. In addition, DOX-Fe3O4 -PEG-PLANPs showed improved internalized into carcinoma cells under magnetic fi eld signifi cantly. In vivo studies demonstrated that the combined therapy under an alternating magnetic fi eld displayed improved therapeutic effect when compared with individual therapies as documented by the delayed tumor growth, inhibition of metastasis, and prolonged survival. The in vitro and in vivo MRI results showed that the multifunctional magnetic nanomaterial had a better MRI signal reduction effect and a higher T2 relaxation rate.

Conclusions: We developed an cervical cancer targeting nano-carrier drug delivery system successfully, which showed perfect excellent T2 contrast magnetic resonance imaging, chemotherapy-sensitizing, tumor targeting , and anti-tumor effect, thus have the potential to be a new theranostic strategy for ovarian cancer patients.

阿霉素（DOX）是一种蒽环类糖苷类抗生素，作为一种DNA插入剂，抑制DNA和RNA的生物合成，被用作单一药物或与其他方案联合实体tumor，但由于其水溶性差应用受到了限制。为了减少该药物的有害作用，可使用各种纳米载体的封装药物传递，新的给药系统和给药途径，以提高其组织选择性。为此制备了涂有氧化铁纳米颗粒和盐酸阿霉素（DOX-Fe3O4 -PEG-PLA-NPs）的多功能磁性纳米颗粒。制备过程如下：

DOX-Fe3O4 -PEG-PLA-NPs的合成油性四氧化三铁

以氯化铁-6H2O为单一铁离子源，采用水热法采用溶剂热法合成MNPS-EDTA。将氯化铁-6H2O溶解在乙二醇中，形成一个清晰的溶液。然后，在混合溶液中加入尿素和EDTA，大力搅拌将混合物放入Tefl内衬不锈钢高压釜中；然后，将高压釜在炉中加热，然后冷却至室温。反应产物用磁铁收集，并在无水乙醇和去离子水中进行清洗和重复使用。最后，将纳米颗粒在干燥24小时。制备了不含EDTA的四氧化三铁磁性纳米颗粒（MNPs）。

正聚乳酸纳米粒子胶束的合成

以二钾（三甲基硅基）酰胺（KHMDS）为引发剂，依次加入环氧乙烷和丙交酯进行阴离子开环聚合，通过酸水解去除保护基团，生成H2N-PEG-b-PLA嵌段共聚物。然后，加入一定比例的二甲基马来酸酐，得到HOOC-PEG-PLA。

DOX-Fe3O4 -PEG-PLA胶束的制备

首先，将PEG5k -PLA5k、DOX和氯仿均匀混合，加入PVA和TPGS的混合物中。在冰浴中使用探针超声波检测形成油水乳化液。最后，将混合物加入到PVA（分散相）中，搅拌过夜，使氯仿挥发，固化PLA球表面。采用100 kD超快离子管进行超快离子浓度清洗。最后，收集样品。

图：DOX-Fe3O4-PEG-PLA流程图

结论：成功制备了涂有氧化铁纳米颗粒和盐酸阿霉素（DOX-Fe3O4 -PEG-PLA-NPs）的多功能磁性纳米颗粒。PEGPLA-NP未检测到有害性作用，在交变磁场作用下，其对tumor的杀伤作用明显增强。药物释放研究表明，在酸性条件下药物释放率增加。此外，DOX-Fe3O4 -PEG-PLA-NPs在磁场作用下对cancer细胞的内化作用有明显改善。多功能磁性纳米材料具有较好的MRI信号降低效果和较高的t2弛豫率。