The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

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.

Iron Oxide Nanoparticle Coatings Dictate Cell Outcomes Despite the Influence of Protein Coronas

“…It has been proposed that the early stages of NP uptake by cells depends mainly on the PC formed on the NP surface, and that this may persist at later stages of uptake, yet coatings may also be key factors in NP uptake by cells. , NPs are typically internalized by cells through endocytosis, which can be divided into two main mechanisms: phagocytosis and pinocytosis. Phagocytosis is used to take up large particles, and it is the first step in the degradation of particles larger than 0.5 μm.…”

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy

“…The effects of plain MNP on EC are still an area of research that is somewhat underdeveloped. Considering their importance in regulating immune responses and their location at the interface between blood and the vessel wall, more knowledge of MNP’s intrinsic activity on EC will improve theranostic applications [ 18 ]. Protocatechuic acid (3,4-dihydroxybenzoic acid; PCA), a phenolic acid found in medicinal plants such as Roselle ( Hibiscus sabdariffa L.) or Japanese ginkgo ( Ginkgo biloba L.), has several therapeutic effects associated with anti-oxidant, anti-bacterial, anti-aging, anti-fibrotic, and anti-inflammatory activity, or even anti-cancer properties at the appropriate concentrations [ 19 ].…”

Ever-Evolving Identity of Magnetic Nanoparticles within Human Cells: The Interplay of Endosomal Confinement, Degradation, Storage, and Neocrystallization

“…[12][13][14][15] However, one major obstacle engineered nanoparticles (including the magnetic ones) still face in their therapeutic mission, concerns a decreased stability and loss of targeting potential in the complex biological environment. [16][17][18][19][20][21] Indeed, despite efforts to customize nanoparticles surface, made with the ambition to deliver nanoparticles to a specific target, the most probable nanoparticles' fate is to end up within endosomes of hepatic and splenic macrophages, where nanoparticles undergo gradual "digestion". Therefore, the topical nano-bio-interface query of the current and following decade relates to processes occurring within the (intra)cellular environment, which profoundly alters the physical and chemical properties of nanoparticles.…”