In this study, a magnetic core–shell modified tumor-targeting nanocarrier (MNPs-PEG–TRA) was engineered and demonstrated for the efficient in vitro and in vivo hyperthermia treatment of breast cancer. Magnetic nanoparticles were used as the initial nanocarriers and modified via PEGylation followed by immobilization of Trastuzumab (TRA) with tumor-targeting function towards cancer cells. The hyperthermia performance of the developed targeting drug delivery system was explored using an in vitro study with SK-BR-3 cancer cells and an in vivo study using animal models (mouse) with DMBA-induced breast cancer. The average size of the engineered system was about 100 nm and its zeta potential was about +13 mV, whereby the stability of the system in biological media is enormously enhanced while the possibility of it being removed via the immune system is diminished. The investigation was pursued based on comparing the changes in growth inhibition rates of HSF 1184, MDA-MB-231, MDA-MB-468 and SK-BR-3 cell lines at different temperatures (37 °C, 40 °C, 42 °C, and 45 °C). Compared with bare MNPs and MNPs-PEG, a remarkably enhanced hyperthermia effect using MNPs-PEG–TRA was observed not only in cultured SK-BR-3 cells in vitro but also in an in vivo DMBA tumor bearing mice model. These results are attributed to an about 4 fold higher concentration of MNPs-PEG–TRA carriers in the tumor site compared to the other organs confirming the considerable potential of the magnetic tumor-targeting hyperthermia concept for breast cancer treatment.

中文翻译：

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曲妥珠单抗装饰纳米颗粒在体外和体内HER2 +乳腺癌的肿瘤靶向热疗

在这项研究中，磁性核-壳修饰的靶向肿瘤的纳米载体（MNPs-PEG-TRA）被设计并证明了对乳腺癌有效的体外和体内高热治疗。磁性纳米颗粒用作初始纳米载体，并通过PEG化修饰，然后将曲妥珠单抗（TRA）固定化，并具有针对癌细胞的肿瘤靶向功能。发达靶向药物递送系统的性能热疗使用的探讨在体外与SK-BR-3肿瘤细胞的研究和体内使用DMBA诱发的乳腺癌的动物模型（小鼠）进行的研究。工程系统的平均大小约为100 nm，ζ电势约为+13 mV，从而大大提高了系统在生物介质中的稳定性，同时降低了通过免疫系统去除系统的可能性。通过比较不同温度（37°C，40°C，42°C）下HSF 1184，MDA-MB-231，MDA-MB-468和SK-BR-3细胞系的生长抑制率变化来进行研究C和45°C）。与裸露的MNP和MNPs-PEG相比，不仅在体外培养的SK-BR-3细胞中而且在体内观察到了使用MNPs-PEG-TRA显着增强的热疗效果。DMBA荷瘤小鼠模型。这些结果归因于与其他器官相比，肿瘤部位中MNPs-PEG-TRA携带者的浓度高约4倍，这证实了靶向磁性磁疗高热概念在乳腺癌治疗中具有巨大潜力。