Journal
JOURNAL OF CONTROLLED RELEASE
Volume 328, Issue -, Pages 59-77Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2020.08.036
Keywords
Iron oxide nanoparticles; Endocytosis; Magnetic resonance imaging; Cytotoxicity; Lysosomes; Apoptosis; Autophagy; Cancer
Funding
- Czech Ministry of Education, Youth and Sports [LTC19040]
- MH CZ - DRO Institute for Clinical and Experimental Medicine - IKEM [IN 00023001]
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Iron oxide nanoparticles (IONPs) were the first generation of nanomaterials that reached real clinic use. Particularly, several IONPs-based magnetic resonance imaging contrast agents gained approval by US Food and Drug Administration (FDA). However, latter body of evidence revealed the overlooked side effects of IONPs, resulting in their withdrawal. Emerging evidence suggests that this happened due to poor understanding of the mechanisms by which IONPs act at the cellular and sub-cellular levels. Recent studies indicate that better understanding of fundamental signal modulations induced by nanomaterials is essential to overcome the clinical problems with nanoparticles. Therefore, in this article we critically review potential mechanisms of IONPs-cell interactions and challenges related with their identification. We describe mechanisms of IONPs-induced toxicity. Ultimately, we demonstrate that knowledge of cellular mechanisms of IONPs action helped to overcome certain translation problems in nanomedicine - we explore potential causes and challenges associated with poor clinical performance of IONPs and propose outlook of how to overcome problems in the field. Our critical analysis implies that a clear understanding of molecular mechanisms of IONPs-cell interactions will provide a basement to increase the likelihood for clinical success of IONPs.
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