Abstract
Over the last 20 years, iron oxide nanoparticles (IONPs) have been the subject of increasing investigation due to their potential use as theranostic agents. Their unique physical properties (physical identity), ample possibilities for surface modifications (synthetic identity), and the complex dynamics of their interaction with biological systems (biological identity) make IONPs a unique and fruitful resource for developing magnetic field-based therapeutic and diagnostic approaches to the treatment of diseases such as cancer. Like all nanomaterials, IONPs also interact with different cell types in vivo, a characteristic that ultimately determines their activity over the short and long term. Cells of the mononuclear phagocytic system (macrophages), dendritic cells (DCs), and endothelial cells (ECs) are engaged in the bulk of IONP encounters in the organism, and also determine IONP biodistribution. Therefore, the biological effects that IONPs trigger in these cells (biological identity) are of utmost importance to better understand and refine the efficacy of IONP-based theranostics. In the present review, which is focused on anti-cancer therapy, we discuss recent findings on the biological identities of IONPs, particularly as concerns their interactions with myeloid, endothelial, and tumor cells. Furthermore, we thoroughly discuss current understandings of the basic molecular mechanisms and complex interactions that govern IONP biological identity, and how these traits could be used as a stepping stone for future research.
Highlights
Iron oxide nanoparticles (IONPs) belong to a family of inorganic nanomaterials that have increasingly become the focus of research over the last decade [1,2]
Based on the premise that IONP degradation products can represent an external source of iron for the cells, the first section of this review provides an overview of the cellular mechanisms driven by iron oxide in a physiological context
Part of the effects that IONP exert on cellular function depends on the iron cation released from theNNaPnoimraotnericaolsr2e0s2.0I,r1o0n, 8c3a7tions engage in cellular iron metabolism machinery and likely disturb redox 7 of 35 homeostasis
Summary
Iron oxide nanoparticles (IONPs) belong to a family of inorganic nanomaterials that have increasingly become the focus of research over the last decade [1,2]. The possibility of functionalizing IONPs with biomolecules such as peptides [14,15], ligands [16], antibodies [17,18], aptamers [19,20], or RNAs [21] further enables IONPs to interact with a specific cell type or tissue; for instance, antibody-functionalized IONPs can target antigen-expressing tumor cells, which allows local application of an alternative magnetic field for the induction of magnetic hyperthermia [22] Understanding these interactions and how they influence the intended application of the synthesized nanoparticle is critical, as such knowledge allows for more rational nanomaterial design but could enable these previously undiscovered characteristics to be harnessed for combinatorial therapies.
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