Magnetic Iron Nanoparticles: Synthesis, Surface Enhancements, and Biological Challenges
Abstract
:1. Introduction
2. Magnetic Nanoparticle Synthesis Methods
2.1. Wet-Chemical Methods
2.1.1. Coprecipitation Synthesis
2.1.2. Thermal Decomposition
2.1.3. Hydrothermal Synthesis
2.1.4. Sol–Gel Synthesis
2.1.5. Microemulsion Synthesis
2.2. Assisted Methods
2.2.1. Sonochemically Assisted
2.2.2. Microwave-Assisted
2.3. Biological Synthesis Routes
2.4. Surface Coating
2.4.1. Silica Coating
2.4.2. Carbon-Based Coatings
2.4.3. Metallic Coatings
2.4.4. Polymer Coatings
2.5. Nanocomposites
3. Biological Challenges
3.1. In Vitro Toxicology
3.2. Ex Vivo Toxicity
3.3. In Vivo Toxicity
4. Regulation and Control
5. Conclusions and Perspective
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Synthesis Route | Temperature (°C) | Environment | Time | Size Control | Shape Control | Efficiency Output | Magnetite (XRD Pattern) | Ref. | |
---|---|---|---|---|---|---|---|---|---|
Aqueous routes | Coprecipitation | <100 | Insert atmosphere | Minutes | Relatively broad | Bad | High | Precursor-dependent | [92,93,94] |
Thermal decomposition | 100–300 | Insert atmosphere | Hours to days | Excellent | Excellent | High | Oxygen-dependent | [95,96,97] | |
Hydrothermal | 150–200 | High pressure | Hours to days | Excellent | Excellent | High | Temperature-dependent | [98] | |
Sol–gel | 100–300 | Ambient | Hours | Good | Good | Medium | Poor magnetite presence | [99,100,101,102] | |
Microemulsion | <100 | Ambient | Hours | Good | Good | Low | Poor magnetite presence | [103,104,105] | |
Assisted routes | Sonochemical assisted | <50 | Ambient | Minutes | Good | Bad | Medium | Cavitation- and frequency-dependent | [106,107] |
Microwaved assisted | 100–200 | Ambient | Minutes to hours | Medium | Good | Medium | High magnetite presence | [108,109] | |
Biologic routes | Bacteria driven | Room temp. | Ambient | Hours to days | Broad | Bad | Low | Biologic-assistant-dependent | [110,111,112] |
Green | Room temp. | Ambient | Minutes | Relatively good | Good | Low | Medium magnetite presence. Leaves nature-dependent | [113,114,115] |
Tissue | Concentration | Morphology | Size | Coating | Methodology | Effect | Ref. |
---|---|---|---|---|---|---|---|
Fibroblast (hTERT human) | 0.1–0.02 mg/mL | Spherical | 7.8–9.6 nm | Dextran, albumin Lactoferrin, ceruloplasmin | BrdU assay | Cellular death | [222,223,224] |
Lung cells (A549) | 20–40 mg/kg | Spherical | 20–107.7 nm | Bare | TB staining, ROS, Comet | Enhancement of free radicals and reduction in the GSH DNA oxidative injuries (Comet) Low—no toxicity (TB, ROS) Increased TP and LDH Non-biomechanical damage Cell Young’s modulus decreased (25–28%) | [225,226] |
Liver rat cell (BAL3A rat) | 20–40 mg/kg 25, 50, 75, 150, 300 µg/g | Spherical | 107.7 nm 20–30 nm | Bare Liposomes PEG | MTT, LDH | Nontoxic below 75 µgmL−1 Nonalcoholic fatty liver disease (NAFLD) inflammation LDH leaking Iron overload affected by NAFLD | [226,227,228] |
Mesenchymal mother cell (MSC human) | 50, 100, 250 mg/mL 25, 50, 100, 150 µg/mL | Spherical | 80–150 nm 48 nm | Protamine sulfate PDA | Comet | No significant effect Increased proliferation index and migration ability | [229,230,231] |
Kidney cells (Cos-7 monkey) | 15 mg/kg 1–100 µg/mL | Spheric-like Ferrofluid | 13–122 nm 9.7 nm | Phospholipid-based polymeric micelles DOX | MTT, MTS | Cell viability reduced Particle charge (+)-induced high cytotoxicity Oxidative stress, reverted by tissue | [232,233,234] |
Macrophage (human) | 2.73 mg/mL | Ferrofluid Ellipsoidal | 320–490 nm | Bare SiO2 | MTS, BrdU assay | Time-dependent cell viability (7 days, 20%) Induced M1 activation | [235,236] |
Nervous system cells (human, PC12) | 0–1000 µg/mL | Spherical Hollow spheres | 5–100 nm | PGA SiO2 Dextran Bare | MTS, LDH | MTS increased production DNA fragmentation, apoptotic Conformational changes in Tau protein Oxidative stress | [237,238,239] |
Endothelial cells (BAECs, HUVECs) | 50 µg/mL 0–100 µg/mL 0, 300, 600 µg/mL | Spherical Spherical–like | 50–600 nm 5–10 nm 10 nm | Bare Dextran PSC | PI staining, Redox | Cellular intake Cell viability 80 ± 3% Promotes cell survival by autophagy Peroxidase-like activity | [240,241,242] |
Cancer (multiple) | 50, 100, 500 µg/mL | Spherical–like | 6 nm | DMSA | MTT | High cell viability >90% Trigger immune response High ROS activity | [240,241,242,243] |
Vascular system (A10 rat) | 50, 100, 200, 400 µg/mL | Spherical–like | 150–160 nm | Bare Citric acid | Redox, MTT | Decreased cell viability Increased actin and calponin expression Concentration-dependent toxicity Migration of EPC reduced | [242,244,245] |
Biological Studies | Type of Assay | Assays in MNPs | Ref. |
---|---|---|---|
In vitro | Suspension (HL60, K562) Monolayers (MCF-7, U87MG) Cultured | CCK8, MTT, TB, LDH, Comet | [268,278] |
Ex vivo | Langendorff isolated system, in silico studies | Perfusion pressure, protein expression, mediator count, liver, spleen, lungs, heart | [250,264,279] |
In vivo | Biodistribution, histological staining | VIP, liver, spleen, lungs, heart | [268,280] |
Organization | Nanomaterial Definition * | Status | Last Meeting/Proposal | Ref. |
---|---|---|---|---|
NANoREG (European Union, EU, European Commission, EC) | Taken from EC: “Any intentionally produced material that has one or more dimensions of the order of 100 nm or less or that is composed of discrete functional parts, either internally or at the surface, many of which have one or more dimensions of the order of 100 nm or less”. | Toxicological data gathering | 2014, updated by NanoFATE in 2022 | [281,282] |
International Organization for Standardization (ISO) | “Any material with any external dimension in the nanoscale or having an internal structure or surface in the nanoscale”. | Terms and vocabulary for nano-objects | 2017 | [283] |
FDA (United States of America, National Nanotechnology Initiative, NNI) | Taken from the NNI: “The understanding and control of matter at dimensions between approximately 1 and 100 nanometers, where unique phenomena enable novel applications”. | Nonbinding recommendations for manufacturers | 2014 | [284,285] |
ECHA (European Union) | “A natural, incidental, or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in size range 1 nm–100 nm”. | Guidance for terms, vocabulary, and sample dispersion and aggregation of nanoforms | Draft 2021 | [286] |
CEPA (Canada) | “Any manufactured substance or product, as well as any component material, ingredient, device, or structure, if it has at least one external dimension that is at or within the nanoscale, or if it has internal or surface structure that is at the nanoscale, or if it has all dimensions that are smaller or larger than the nanoscale and exhibits at least one nanoscale property or phenomenon”. | Guidance framework for adapting nanomaterials to existing practices | Draft 2022 | [287] |
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Vargas-Ortiz, J.R.; Gonzalez, C.; Esquivel, K. Magnetic Iron Nanoparticles: Synthesis, Surface Enhancements, and Biological Challenges. Processes 2022, 10, 2282. https://doi.org/10.3390/pr10112282
Vargas-Ortiz JR, Gonzalez C, Esquivel K. Magnetic Iron Nanoparticles: Synthesis, Surface Enhancements, and Biological Challenges. Processes. 2022; 10(11):2282. https://doi.org/10.3390/pr10112282
Chicago/Turabian StyleVargas-Ortiz, Jesús Roberto, Carmen Gonzalez, and Karen Esquivel. 2022. "Magnetic Iron Nanoparticles: Synthesis, Surface Enhancements, and Biological Challenges" Processes 10, no. 11: 2282. https://doi.org/10.3390/pr10112282