The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies
Abstract
:1. Introduction
2. Iron Oxide-Driven Biological Activities: Cellular Iron Metabolism and Reactive Oxygen Species
2.1. Cellular Components of Iron Metabolism: Macrophages
2.2. Cellular Components of Iron Metabolism: Endothelial Cells
2.3. Iron Homeostasis and Cancer Cells
2.4. Iron Oxide and Redox Homeostasis
3. Iron Oxide Nanoparticle Biodegradation
3.1. IONP Biodegradation and Biological Identity
3.2. IONP Degradation and Protein Corona
3.3. Endocytosis and IONP Degradation
3.4. IONP Biodegradation by Cellular Machinery
4. IONP Effects is Dependent on Cell Type and Status
4.1. IONPs and Myeloid Cells
4.1.1. Iron Metabolism and Macrophage Polarization
4.1.2. IONP Recognition by Macrophages and Activation
4.1.3. IONPs and Dendritic Cells (DC)
4.2. Iron Oxide and Functions of Endothelial Cells
4.3. Tumor Microenvironment and Iron Oxide Nanoparticles
5. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Identity | Concept |
---|---|
Physical | This refers to the basic physical properties that define the nanoparticle core, e.g., superparamagnetism, plasmonic, or fluorescence [23,24]. |
Synthetic | Refers to the intrinsic physicochemical properties of the engineered surface coating, as well as its size, shape, and surface chemistry post-synthesis (surface coating modifications) [25,26,27,28]. |
Biological | Refers to the size and aggregation state of the nanoparticles in physiological fluids (i.e., blood, tissue micro-environment, intracellular space) and the biomolecule (e.g., protein) corona. Biological identity varies with changes in synthetic identity, microenvironment, and interaction time [27,28,29,30]. |
Iron Oxide Nanoparticle | Physical Identity | Synthetic Identity (Surface Coating) | Biological Fluid | Biological Identity |
---|---|---|---|---|
IONP@Glu [100] | Fe3O4 | Poly(maleic anhydride-alt-1-octadecene)-EDC-glucose | Serum protein | Protein AMBP Coagulation factor XI Fibrinogen beta chain C4b-binding protein α-like Profilin-1 |
IONP@PEG [100] | Fe3O4 | Poly(maleic anhydride-alt-1-octadecene)-EDC-PEG | Serum protein | Actin, aortic smooth muscle Keratin, type I cytoskeletal 10 Keratin, type II cytoskeletal 7 Lysozyme C Fructose-biphosphate aldolase |
IONP@PMAO [100] | Fe3O4 | Poly(maleic anhydride-alt-1-octadecene) | Serum protein | Fibrinogen α-chain Tubulin α-4A chain Adenylyl cyclase-associated protein Macrophage migratory inhibitory factor Ectonucleotide Pyrophosphatase/phosphodiesterase family Member 2 |
ZW-L1@PAA-USPIONs [104] | Fe3O4 | ZW-L1@PAA | 80% human serum | α-2-Macroglobulin precursor Apolipoprotein C-II precursor |
ZW-L2@PAA-USPIONs [104] | Fe3O4 | ZW-L2@PAA | 80% human serum | Apolipoprotein C-II precursor Apolipoprotein A-I preprotein Apolipoprotein A-II preprotein Apolipoprotein A-IV precursor Serum albumin preprotein |
ZW-L3@PAA-USPIONs [104] | Fe3O4 | ZW-L3@PAA | 80% human serum | Apolipoprotein B-100 precursor Vitronectin precursor Complement C3 precursor Serum albumin preprotein Apolipoprotein A-II preprotein |
PAA@USPIONs [104] | Fe3O4 | PAA | 80% human serum | α-2-Macroglobulin precursor Apolipoprotein A-I preprotein Apolipoprotein C-III precursor Complement C3 precursor Apolipoprotein B-100 precursor |
Rh-Citrate@ IONPs [105] | Fe3O4 | Rhodium citrate | Human blood serum | Human serum albumin Complement C5 A-Kinase anchor protein 13 Apolipoprotein A-I α-2-HS-glycoprotein |
@IONPs/PVP @IONPs/PEG @IONPs [95] | Fe3O4 | Polyvinylpyrrolidone (PVA) or polyethylene glycol (PEG) | Human plasma | 14-3-3-Protein β/α 14-3-3-Protein ε Protein kinase C inhibitor protein 1 78 kDa glucose-regulated protein (GRP-78) Actin, aortic smooth muscle (α-actin-2) |
CSNP [97] | Fe3O4 | Silica | Human plasma | Fibrinogen b Fibrinogen g Fibrinogen a Vitronectin Histidine-rich glycoprotein |
Nanomag-D@SPIO [97] | Fe3O4 | Dextran | Human plasma | Kininogen 1 microtubule-associated ser/thr Kinase-like Actin, beta Integrin, alpha 2b Pro-platelet basic protein |
IONP Name | Physical Identity | Synthetic Identity (Surface Coating) | Biological Identity | Endocytic Pathways | Receptors | Cell Type | References |
---|---|---|---|---|---|---|---|
Silica@IONP | Fe2O3 | SiO2 | N.A. | Caveolin-dependent | CDC42 | HeLa | [120] |
PEI@SPIONs | Fe3O4 | Polyethyleneimine (PEI) | N.A. | Clathrin-dependent and caveolin-dependent | TLR4 | RAW264.7 and Pan02 | [121,122] |
FA–PEI@SPIONs | Fe3O4 | PEI | Folic acid | Clathrin-dependent | Folic acid receptor | HeLa | [123] |
BP-D@IONPs | Fe2O3 | DMSA and BODIPY | With/out 10% serum (aggregates) | Endocytosis-independent and clathrin-dependent | N.A. | Oligodendroglial (OLN-93) | [124] |
Ferumoxides | Fe3O4 | Dextran | N.A. | Clathrin-dependent | SR-A | THP-1 | [125] |
DMSA@SPIONs | Fe3O4 | DMSA | N.A. | Clathrin-dependent (<200 nm) and macropinocytosis (aggregates > 200 nm) | N.A. | MCF-7 | [126] |
Carboxydextran@USPION | Fe3O4 | Carboxydextran | N.A. | Clathrin-dependent | SR-A | Human macrophages | [127] |
PLL@IONPs | N.A. | Poly-L-lysine | N.A. | Clathrin-dependent | TfR | HeLa | [128] |
Carboxymethyl-dextran@IONPs | N.A | Carboxymethyl-dextran | Serum (protein corona) | Clathrin-dependent and caveolin-dependent | N.A. | CaCo-2 | [129] |
Aminosilane@IONPs | Fe3O4 | Aminosilane | N.A. | Phagocytosis | N.A. | Lung cancer cell, SPC-A1 | [130] |
DMSA@IONPs | γ-Fe2O3 | DMSA | N.A. | Clathrin-dependent, caveolin-dependent, and macropinocytosis | N.A. | RAW264.7 | [131] |
Maghemite–rhodium citrate NPs | γ-Fe2O3 | Rh-citrate | N.A. | Clathrin-dependent | N.A. | MCF-7, MDA-MB-231, and HNTMCs | [132] |
Aminodextran@IONPs | Fe3O4 | Aminodextran | N.A. | Macropinocytosis | N.A. | A-549 | [133] |
PEI@IONPs | Fe3O4 | PEI | N.A. | Adsorptive endocytosis | N.A. | RAW264.7 | [116] |
PEG@IONPs | Fe3O4 | Polyethylene glycol | N.A. | Receptor-mediated endocytosis | N.A. | RAW264.7 | [116] |
Iron Oxide Nanoparticles | Physical Identity | Synthetic Identity (Surface Coating) | Cell Type | Described Effects | Mechanism |
---|---|---|---|---|---|
Carboxymaltose@Fe2O3 [153] | Fe2O3 | Carboxymaltose | J774A.1 Primary macrophages | Inhibits LPS-induced NO Inhibits IL-6 and TNFα secretion Hampers phagocytosis | Decreased free glutathione |
PMA@IONPs (4 and 14 nm) [154] | Fe3O4 | PMA | Hamper cell viability Promote extensive vacuolization Induce TNFα, CD86 and inhibit CD206 gene expression | Promotion of extensive vacuolization | |
PEGylated PMA@IONPs (4 and 14 nm) [154] | Fe3O4 | PEGylates PMA | RAW264.7 | Promote cell proliferation Promote extensive vacuolization Induce TNFα, CD86 and inhibit CD206 gene expression | Promotion of extensive vacuolization |
PDSCE@IONPs [155] | γ-Fe2O3 | Polydextrose sorbitol carboxymethyl-ether | In vivo and RAW264.7 | Reduce the level of LPS-induced injury Induce a large amount of IL-10 Trigger autophagy | Promotion of autophagy through Cav1-Notch1/HES1 |
Carboxydextran@IONPs [156] | Fe3O4 | Carboxydextran | In vivo local administration and J774.2 | Downmodulate CD86, MHC-II, Arg1 and CD163 expression (transient) Hamper phagocytosis (transient) | N.A. |
SiO2@IONPs [157] | γ-Fe2O3 | SiO2 | Peritoneal macrophages | Increase γH2AX (marker for double-strand break) Increase IL-10 production | N.A. |
Resovist [158] | Fe3O4 γ-Fe2O3 | Carboxydextran | Primary macrophages and RAW264.7 | Induce autophagy Induce pro-inflammatory gene expression (TNFα, IL-12, MIP-1-α, etc.) | Promote autophagy through TLR4-p38-Nrf2-p62 signaling pathway |
Feraheme [158] | Fe3O4 | Carboxymethyl dextran | Induce autophagy Induce pro-inflammatory gene expression (TNFα, IL-12, MIP-1-α, etc.) | Promote autophagy through TLR4-p38-Nrf2-p62 signaling pathway | |
DMSA@IONPs [159] | Fe3O4 | DMSA | RAW264.7 | Induce pro-inflammatory cytokines Promote cell proliferation Promote macrophage migration Promote macrophage-driven Hepa1-6 cell killing | N.A. |
PEI@IONPs [121] | Fe3O4 γ-Fe2O3 | PEI | RAW264.7, THP-1, and primary peritoneal macrophages | Induce pro-inflammatory cytokines (IL-12, IL-1β, TNFα, etc.) Activate macrophages (increase CD40, CD80, CD86 and I-A/I-E) Activate the MAPK-dependent pathway Promote podosome formation and reduce ECM degradation | At least part of the effects are mediated by production of ROS and activation of TLR-4 |
Citrate@Fe3O4 of different shape (octopod, plate, cube, sphere) [160] | Mn-doped Fe3O4 | Citrate | Bone marrow-derived macrophages (BMDMs) | Activate inflammasome (IL-1β) Induce pyroptosis Induce ROS production In this order: Octopod > plate > cube > sphere | Lysosome damage, ROS production, and K+ efflux, partially mediated by NLPR3 |
Alkyl-PEI@IONPs (30, 80, and 120 nm) [161] | Fe3O4 | Alkyl-PEI | BMDMs | Induce IL-1β nm > 80 nm > 120 nm) Lysosome damage ROS production | Modulated by ROS |
Fe2O3@D-SiO2 [162] | Fe2O3 | SiO2 | RAW264.7 | Increase CD80, CD86 and CD64 | Activate NF-κB and IRF5 |
Fe3O4@D-SiO2 [162] | Fe3O4 | SiO2 | RAW264.7 | Negligible effect | N.A. |
DMSA@IONPs [163] | Fe3O4 | DMSA | M2-like THP1 BMDMs (M2) | Induce ROS production Change Fe metabolism to an iron-replete status Reduce Mac3, CD80 Increase IL-10 production Decrease migration but increase invasion | Activation of MAPK signaling |
APS@IONPs [163] | Fe3O4 | 3-Aminopropyl triethoxysilane | M2-like THP1 BMDMs (M2) | Induce ROS production Change Fe metabolism to an iron-replete status Reduce Mac3, CD80 Increase IL-10 production Decrease migration but increase invasion | Activation of MAPK signaling |
AD@IONPs [163] | Fe3O4 | Aminodextran | M2-like THP1 BMDMs (M2) | Induce ROS production Change Fe metabolism to an iron-replete status Reduce Mac3 Decrease migration but increase invasion | Activation of MAPK signaling |
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Mulens-Arias, V.; Rojas, J.M.; Barber, D.F. The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies. Nanomaterials 2020, 10, 837. https://doi.org/10.3390/nano10050837
Mulens-Arias V, Rojas JM, Barber DF. The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies. Nanomaterials. 2020; 10(5):837. https://doi.org/10.3390/nano10050837
Chicago/Turabian StyleMulens-Arias, Vladimir, José Manuel Rojas, and Domingo F. Barber. 2020. "The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies" Nanomaterials 10, no. 5: 837. https://doi.org/10.3390/nano10050837