Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran 1234567, Iran.
Department of Animal Science, Faculty of Agriculture, University of Tabriz, Tabriz 5166616471, Iran.
ACS Biomater Sci Eng. 2020 Jun 8;6(6):3574-3584. doi: 10.1021/acsbiomaterials.0c00086. Epub 2020 May 13.
Despite successes in breast cancer treatment, the incidence of metastasis, drug resistance, and toxicity limit the efficacy of current therapeutic modalities. Herein, by designing lactoferrin-doxorubicin-mesoporous maghemite nanoparticles (Lf-Doxo-MMNPs), we not only provided targeted drug delivery (TDD), but also enabled chemotherapy/magnetic field/photothermal (chemo/MF/PTT) combination therapy to mitigate breast cancer proliferation and metastasis. After synthesizing Lf-Doxo-MMNPs by hydrothermal method and characterizing their features, we examined their effect on the body weight, tumor growth inhibition (TGI), tumor size, Doxo and iron biodistribution, histopathology of metastatic lung tissue, heart tissue, and breast tumor, cell death mechanisms, and metastatic gene expression. The results showed that Lf-Doxo-MMNPs, in addition to enhancing anticancer effects , resulted in a significant increase in body weight, TGI, and targeted drug delivery (TDD). In addition to the significant impacts of Lf-Doxo-MMNPs on the reduction of cancer cell proliferation, their application in chemo/MF/PTT combination therapy has a remarkable effect on the antimetastatic activities against breast tumors. Indeed, chemo/MF/PTT combination therapy exhibited the most reduction in metastatic activity of breast cancer based on controlling C-X-C motif chemokine ligand 12 (CXCL12) and chemokine receptor 7 (CXCR7) mRNA expression. In conclusion, the promising results of Doxo accumulation, reduced cancer cell proliferation, and inhibition of metastatic mRNA expression indicated that MMNPs provide a potential platform for combined therapeutic approaches.
尽管在乳腺癌治疗方面取得了成功，但转移、耐药性和毒性的发生率限制了当前治疗方式的疗效。在这里，通过设计乳铁蛋白-阿霉素-介孔磁铁矿纳米粒子（Lf-Doxo-MMNPs），我们不仅提供了靶向药物递送（TDD），还实现了化疗/磁场/光热（chemo/MF/PTT）联合治疗，以减轻乳腺癌的增殖和转移。通过水热法合成 Lf-Doxo-MMNPs 并对其特征进行表征后，我们研究了它们对体重、肿瘤生长抑制（TGI）、肿瘤大小、Doxo 和铁的生物分布、转移性肺组织、心脏组织和乳腺癌的组织病理学、细胞死亡机制和转移性基因表达的影响。结果表明，Lf-Doxo-MMNPs 除了增强抗癌作用外，还显著增加了体重、TGI 和靶向药物递送（TDD）。除了 Lf-Doxo-MMNPs 对降低癌细胞增殖的显著影响外，它们在化疗/MF/PTT 联合治疗中的应用对乳腺癌的抗转移活性也有显著效果。事实上，基于控制 C-X-C 基序趋化因子配体 12（CXCL12）和趋化因子受体 7（CXCR7）mRNA 表达，化疗/MF/PTT 联合治疗在降低乳腺癌的转移活性方面效果最显著。总之，Doxo 积累、降低癌细胞增殖和抑制转移性 mRNA 表达的有希望的结果表明，MMNPs 为联合治疗方法提供了一个潜在的平台。
