Iron oxide (IO) nanoparticles hold great promise as diagnostic and therapeutic agents in oncology. Their intrinsic physical
properties make IO nanoparticles particularly interesting for simultaneous drug delivery, molecular imaging, and applications such as localized
hyperthermia. Multiple non-targeted IO nanoparticle preparations have entered clinical trials, but more exciting, new tumortargeted
IO nanoparticle preparations are currently being tested in preclinical settings. This paper will analyze the challenges faced by
this new theranostic modality, with a specific focus on the interactions of IO nanoparticles with the innate and adaptive immune systems,
and their effect on nanoparticle biodistribution and tumor targeting. Next, we will review the critical need for innovative surface chemistry
solutions and strategies to overcome the immune interactions that prevent existing tumor-targeted IO preparations from entering clinical
trials. Finally, we will provide an outlook for the future role of IO nanoparticles in oncology, which have the promise of becoming
significant contributors to improved diagnosis and treatment of cancer patients.
Keywords: Iron oxide nanoparticles, tumor targeting, immunology, inflammation, macrophage, nanoparticle surface chemistry, cancer theranostics.
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