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

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

doi:10.3389/fmed.2021.738775

Abstract

Objective: The purpose of this study was to investigate the anticancer activity and the potential imaging use of the innovative combination of magnetic nanoparticles (MNPs)-Fe3O4, paclitaxel (PTX), and trastuzumab (Herceptin) in HER2-positive breast cancer.Methods: MNPs-Fe3O4 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-Fe3O4 were observed under transmission electron microscopy (TEM). Effects of PTX-Herceptin-MNPs-Fe3O4 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-Fe3O4 on tumor growth by measuring tumor size and calculating inhibition rate with immunohistochemistry analysis further performed, and analyzed MNPs-Fe3O4 accumulation in tumor lesions using in vivo magnetic resonance imaging and in vivo fluorescence imaging.Results: Most MNPs were in spherical shape of about 10 nm in diameter observed under TEM. PTX-Herceptin-MNPs-Fe3O4 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 in vivo tumor xenograft model showed that tumor inhibition rate in the PTX-Herceptin-MNPs-Fe3O4 group was higher than in the PTX-Herceptin group. Furthermore, PTX-Herceptin-MNPs-Fe3O4 enhanced the T2 imaging contrast enhancement effect on tumors in tumor-bearing mice.Conclusion: The novel PTX-Herceptin-MNPs-Fe3O4 combination may represent a promising alternative breast cancer treatment strategy and may facilitate tumor imaging.

Highlights

Breast cancer (BC) is one of the most common cancers, and the second leading cause of cancer-related mortality worldwide, representing a grievous threat to women’s health and quality of life [1, 2]
Most magnetic nanoparticles (MNPs) were in spherical shape of about 10 nm in diameter observed under transmission electron microscopy (TEM)
The in vivo tumor xenograft model showed that tumor inhibition rate in the PTX-Herceptin-MNPs-Fe3O4 group was higher than in the PTX-Herceptin group

Summary

Introduction

Breast cancer (BC) is one of the most common cancers, and the second leading cause of cancer-related mortality worldwide, representing a grievous threat to women’s health and quality of life [1, 2]. Human epidermal growth factor receptor-2 (HER-2) positive breast cancer accounts for 20–25% of all BC molecular subtypes. Its associations with aggressive tumor growth and inferior prognosis have been well-studied [3]. HER-2 is a protooncogene that is negatively or minimally expressed in normal tissues and its overexpression could lead to excessive growth and enhanced invasiveness of tumor cells. HER-2-targeted agents effectively inhibit HER-2 expression, thereby achieving anti-tumor effect. Trastuzumab is a humanized anti-HER-2 monoclonal antibody that was first used in the therapy of HER-2 positive BC with changing its natural biology

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Discussion

Conclusion