Source abstract
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.
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Affiliations
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
Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar
Biomedical Research Center, Qatar University, Doha 2713, Qatar
Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia
Department of Bioengineering, Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong 519041, China
School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong 521041, China
Funding
Natural Science Foundation of Guangdong Province · Guizhou Science and Technology Foundation of China · Science and Technology Planning Project of Guangdong