Treatment of Breast Cancer-Bearing BALB/c Mice with Magnetic Hyperthermia using Dendrimer Functionalized Iron-Oxide Nanoparticles

Marzieh Salimi,Reza Saber,Saeed Sarkar,Mansoureh Hashemi

doi:10.3390/nano10112310

Marzieh Salimi, Reza Saber + Show 2 more

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https://doi.org/10.3390/nano10112310

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Abstract

The development of novel nanoparticles for diagnostic and therapeutic applications has been one of the most crucial challenges in cancer theranostics for the last decades. Herein, we functionalized iron oxide nanoparticles (IONPs) with the fourth generation (G4) of poly amidoamine (PAMAM) dendrimers (G4@IONPs) for magnetic hyperthermia treatment of breast cancer in Bagg albino strain C (BALB/c)mice. The survival of breast cancer cells significantly decreased after incubation with G4@IONPs and exposure to an alternating magnetic field (AMF) due to apoptosis and elevation of Bax (Bcl-2 associated X)/Bcl-2(B-cell lymphoma 2) ratio. After intratumoral injection of G4@IONPs, tumor-bearing BALB/c mice were exposed to AMF for 20 min; this procedure was repeated three times every other day. After the last treatment, tumor size was measured every three days. Histopathological and Immunohistochemical studies were performed on the liver, lung, and tumor tissues in treated and control mice. The results did not show any metastatic cells in the liver and lung tissues in the treatment group, while the control mice tissues contained metastatic breast cancer cells. Furthermore, the findings of the present study showed that magnetic hyperthermia treatment inhibited tumor growth by increasing cancer cell apoptosis, as well as reducing the tumor angiogenesis.

Highlights

Breast cancer is the most common cancer in women both in developed and developing countries
The results showed that magnetic hyperthermia using G4@iron oxide nanoparticles (IONPs) could effectively demolish breast cancer cells by increasing apoptosis and inhibit tumor growth by reducing the tumor angiogenesis and perfusion
Zeta potential is an indicator of surface charge that can be used to predict the magnetic nanoparticles (MNPs) solution stability and is a crucial parameter for the interaction of G4@IONPs with biological systems in vivo

Summary

Introduction

Breast cancer is the most common cancer in women both in developed and developing countries. The most common treatment methods for breast cancer, e.g., radiation therapy, surgery, and chemotherapy, possess several side effects, such as secondary cancer, tumor recurrence, and normal tissue damage. The temperature of the tumor tissue rises 5–7 ◦C above the normal temperature of the body [8]. In this situation and considering that cancer cells are more sensitive to heat, these cells will be damaged while healthy cells can be spared [9,10]

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