AUTHOR=Guo Liting , Zhang Hongming , Liu Ping , Mi Tianai , Ha Da , Su Li , Huang Lei , Shi Yan , Zhang Jun 

TITLE=Preclinical Assessment of Paclitaxel- and Trastuzumab-Delivering Magnetic Nanoparticles Fe3O4 for Treatment and Imaging of HER2-Positive Breast Cancer

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.738775

DOI=10.3389/fmed.2021.738775

ISSN=2296-858X

ABSTRACT=<p><bold>Objective:</bold> The purpose of this study was to investigate the anticancer activity and the potential imaging use of the innovative combination of magnetic nanoparticles (MNPs)-Fe<sub>3</sub>O<sub>4</sub>, paclitaxel (PTX), and trastuzumab (Herceptin) in HER2-positive breast cancer.</p><p><bold>Methods:</bold> MNPs-Fe<sub>3</sub>O<sub>4</sub> was synthesized and underwent water phase transfer and hydrophobic molecular loading, and its surface was then coupled with Herceptin mono-antibody. The morphological characteristics of MNPs-Fe<sub>3</sub>O<sub>4</sub> were observed under transmission electron microscopy (TEM). Effects of PTX-Herceptin-MNPs-Fe<sub>3</sub>O<sub>4</sub> on breast cancer cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,4-diphenyltetrazolium bromide assay and the flow cytometric apoptosis assay. To establish a xenograft model, we injected breast cancer SK-BR-3 cells into the left thighs of nude mice. We measured the effect of PTX-Herceptin-MNPs-Fe<sub>3</sub>O<sub>4</sub> on tumor growth by measuring tumor size and calculating inhibition rate with immunohistochemistry analysis further performed, and analyzed MNPs-Fe<sub>3</sub>O<sub>4</sub> accumulation in tumor lesions using <italic>in vivo</italic> magnetic resonance imaging and <italic>in vivo</italic> fluorescence imaging.</p><p><bold>Results:</bold> Most MNPs were in spherical shape of about 10 nm in diameter observed under TEM. PTX-Herceptin-MNPs-Fe<sub>3</sub>O<sub>4</sub> showed greater cytotoxic effects, and induced a higher apoptosis rate of SK-BR-3 cells than all the other groups, with corresponding changes of apoptosis-related proteins. Meanwhile, the <italic>in vivo</italic> tumor xenograft model showed that tumor inhibition rate in the PTX-Herceptin-MNPs-Fe<sub>3</sub>O<sub>4</sub> group was higher than in the PTX-Herceptin group. Furthermore, PTX-Herceptin-MNPs-Fe<sub>3</sub>O<sub>4</sub> enhanced the T2 imaging contrast enhancement effect on tumors in tumor-bearing mice.</p><p><bold>Conclusion:</bold> The novel PTX-Herceptin-MNPs-Fe<sub>3</sub>O<sub>4</sub> combination may represent a promising alternative breast cancer treatment strategy and may facilitate tumor imaging.</p>