Oxi-Redox Selective Breast Cancer Treatment: An In Vitro Study of Theranostic In-Based Oxide Nanoparticles for Controlled Generation or Prevention of Oxidative Stress

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Hsu, Nai-Sheng
Tehei, Moeava
Hossain, Md Shahriar
Rosenfeld, Anatoly
Shiddiky, Muhammad JA
Sluyter, Ronald
Dou, Shi Xue
Yamauchi, Yusuke
Konstantinov, Konstantin
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2021
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Abstract

In this article, we demonstrate that specifically engineered oxide nanoparticles (NPs) have the potential to act as theranostic materials that are able to generate or prevent oxidative stress through their oxi-redox activity in various types of malignant and nonmalignant cells. The oxi-redox activity is related to the type and presence of surface defects, which is modified with appropriate synthesis conditions. In the present work, we used MDA-MB-231 and MCF-7 human breast cancer cells and nonmalignant MCF-10A human breast cells to demonstrate how controlled oxidative stress mediated by specifically nanoengineered indium tin oxide (ITO) NPs can selectively induce cell death in the cancer cells while reducing the oxidative stress in the normal cells and supporting their proliferation. The ITO NPs are also promising nanotheranostic materials for cancer therapy and contrast agents because of their multimodal imaging capabilities. We demonstrate that the synthesized ITO NPs can selectively increase the generation of reactive oxygen species (ROS) in both breast tumor cell lines, resulting in activation of apoptosis, and can also greatly suppress the cellular proliferation in both types of tumor cells. In contrast, the ITO NPs exhibit ROS scavenging-like behavior, significantly decreasing the ROS levels in MCF-10A cells exposed to the additional ROS, hydrogen peroxide (H2O2), so that they protect the proliferation of nonmalignant MCF-10A cells from ROS damage. In addition, fluorescent microscopy images revealed that the ITO NPs emit strong fluorescence that could be used to reveal their location. Moreover, computed tomography imaging demonstrated that the ITO NPs exhibited a comparable capability toward anatomical contrast enhancement. These results suggest that the synthesized ITO NPs have the potential to be a novel selective therapeutic agent with a multimodal imaging property for anticancer treatment.

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ACS Applied Materials & Interfaces

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials & Interfaces, © 2021 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsami.0c17326

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This publication has been entered as an advanced online version in Griffith Research Online.

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Chemical sciences

Engineering

Oncology and carcinogenesis

breast cancer treatment

controlled ROS scavenging/generation

engineered ITO NPs

multifunctional theranostic system

surface defects

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Hsu, N-S; Tehei, M; Hossain, MS; Rosenfeld, A; Shiddiky, MJA; Sluyter, R; Dou, SX; Yamauchi, Y; Konstantinov, K, Oxi-Redox Selective Breast Cancer Treatment: An In Vitro Study of Theranostic In-Based Oxide Nanoparticles for Controlled Generation or Prevention of Oxidative Stress, ACS Applied Materials & Interfaces, 2021

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