Antimetastatic Activity of Lactoferrin-Coated Mesoporous Maghemite Nanoparticles in Breast Cancer Enabled by Combination Therapy

Abstract

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 in vitro, 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.