Abstract

Traditional concepts of life sciences consider oxidative stress as a fundamental process of aging and various diseases including cancer, whereas traditional medicine recommends dietary intake of iron to support physiological functions of the organism. However, due to its strong pro-oxidative capacity, if not controlled well, iron can trigger harmful oxidative stress manifested eventually by toxic chain reactions of lipid peroxidation. Such effects of iron are considered to be major disadvantages of uncontrolled iron usage, although ferroptosis seems to be an important defense mechanism attenuating cancer development. Therefore, a variety of iron-containing nanoparticles were developed for experimental radio-, chemo-, and photodynamic as well as magnetic dynamic nanosystems that alter redox homeostasis in cancer cells. Moreover, studies carried over recent decades have revealed that even the end products of lipid peroxidation, represented by 4-hydroxynonenal (4-HNE), could have desirable effects even acting as kinds of selective anticancer substances produced by non-malignant cells for defense again invading cancer. Therefore, advanced nanotechnologies should be developed for using iron to trigger targeted lipid peroxidation as an anticancer option of integrative biomedicine.

Highlights

  • One of the most challenging health conditions is cancer, and nanotechnology has provided new opportunities for the development of more efficient treatment procedures

  • Iron is necessary for numerous physiological processes but could be an important trigger of oxidative stress, especially of lipid peroxidation, contributing either to carcinogenesis or to toxicity of anticancer treatments

  • Ferroptosis acts as a potential natural anticancer defense mechanism that uses iron to generate reactive oxygen species (ROS) and lipid peroxidation and eventually destroy cancer cells

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Summary

Introduction

One of the most challenging health conditions is cancer, and nanotechnology has provided new opportunities for the development of more efficient treatment procedures. Iron containing nanoparticles including iron oxide nanoparticles (IONPs), are promising tools for anticancer therapies. On the basis of the different oxidation states and crystalline structures, IONPs comprise magnetite (Fe3 O4 ), maghemite (γ-Fe2 O3 ), and hematite (α-Fe2 O3 ). IONPs made up of magnetite and maghemite have great biocompatibility with superparamagnetic properties. A variety of iron containing nanosystems, as potent agents in anticancer treatment, have been described in the literature. Iron oxide nanoparticle properties have been reported to be useful for various biomedical purposes, such are targeted drug delivery, bioimaging, biosensors, and hyperthermia [1], while some are approved by Food and Drug Administration (FDA) [2,3]. NanoTherm for management of glioblastoma and Ferumoxytol for iron deficiency treatment are among the FDA approved iron oxide containing nanomedicines.

Iron Regulated Cellular Processes
Ferroptosis as a Target for Oncotherapy
The Lipid Peroxidation Product 4-Hydroxynonenal
Iron-Containing Nanoparticles in Oncotherapy
Oproduction
Conclusions
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