Stabile vandige suspensioner af mangan ferrite klynger med tunable nanoskala dimension og sammensætning
Summary
Vi rapporterer en one-pot hydrotermisk syntese af mangan ferrit klynger (MFC), der tilbyder uafhængig kontrol over materiale dimension og sammensætning. Magnetisk adskillelse muliggør hurtig rensning, mens overfladefunktionalisering ved hjælp af sulfonerede polymerer sikrer, at materialerne ikke aggregeres i biologisk relevant medium. De resulterende produkter er godt placeret til biomedicinske applikationer.
Abstract
Mangan ferrit klynger (MFC’ er) er sfæriske samlinger af tiere til hundredvis af primære nanokrystaller, hvis magnetiske egenskaber er værdifulde i forskellige applikationer. Her beskriver vi, hvordan disse materialer dannes i en hydrotermisk proces, der tillader uafhængig styring af produktklyngens størrelse (fra 30 til 120 nm) og manganindholdet i det resulterende materiale. Parametre som den samlede mængde vand, der tilsættes de alkoholiske reaktionsmedier, og forholdet mellem mangan og jernprækursor er vigtige faktorer for at opnå flere typer MFC-nanoskalaprodukter. En hurtig rensningsmetode bruger magnetisk adskillelse til at genvinde materialerne, hvilket gør produktionen af gram magnetiske nanomaterialer ret effektiv. Vi overvinder udfordringen med magnetisk nanomaterialeaggregation ved at anvende stærkt ladede sulfonatpolymer på overfladen af disse nanomaterialer, der giver kolloidt stabile MFC’er, der forbliver ikke-aggregerede selv i meget saltholdige miljøer. Disse ikke-aggregerende, ensartede og tunable materialer er fremragende potentielle materialer til biomedicinske og miljømæssige anvendelser.
Introduction
Inddragelsen af mangan som dopant i et jernoxidgitter kan under passende forhold øge materialets magnetisering på høje påførte marker sammenlignet med rene jernoxider. Som følge heraf er mangan ferrit (MnxFe3-xO4) nanopartikler meget ønskelige magnetiske nanomaterialer på grund af deres høje mætningsmagnetisering, stærk respons på eksterne felter og lav cytotoksicitet1,2,3,4,5. Både enkelt domæne nanokrystaller samt klynger af disse nanokrystaller, benævnt multidomain partikler, er blevet undersøgt i forskellige biomedicinske applikationer, herunder lægemiddellevering, magnetisk hypertermi til kræftbehandling, og magnetisk resonans imaging (MRI)6,7,8. For eksempel brugte Hyeon-gruppen i 2017 enkeltdomænemangan ferrit nanopartikler som Fenton-katalysator for at fremkalde kræfthypoti og udnyttede materialets T2contrast til MR-sporing9. Det er overraskende i lyset af disse og andre positive undersøgelser af ferrit materialer, at der er få in vivo demonstrationer i forhold til ren jernoxid (Fe3O4) nanomaterialer, og ingen rapporterede anvendelser hos mennesker9,10.
En enorm udfordring i forbindelse med oversættelsen af funktionerne i ferrit nanomaterialer til klinikken er dannelsen af ensartede, ikke-aggregerende, nanoskala klynger11,12,13,14. Mens konventionelle syntetiske tilgange til monodomain nanokrystaller er veludviklede, multidomain klynger af den type interesse i dette arbejde er ikke let produceres på en ensartet og kontrolleret måde15,16. Derudover er ferritsammensætningen normalt ikke-stoichiometrisk og ikke blot relateret til startkoncentrationen af prækursorerne, og dette kan yderligere skjule systematisk strukturfunktionskarakterisering af disse materialer9,12,13,17. Her tager vi fat på disse spørgsmål ved at demonstrere en syntetisk tilgang, der giver uafhængig kontrol over både klyngedimensionen og sammensætningen af mangan ferrite nanomaterialer.
Dette arbejde giver også et middel til at overvinde den dårlige kolloide stabilitet af ferrit nanomaterialer18,19,20. Magnetiske nanopartikler er generelt tilbøjelige til sammenlægning på grund af stærk partikel-partikel attraktion; ferrites lider mere af dette problem, da deres større netmagnetisering forstærker partikelsammenlægning. I relevante biologiske medier giver disse materialer store nok aggregater til, at materialerne hurtigt indsamler sig, hvilket begrænser deres eksponeringsveje for dyr eller mennesker20,21,22. Hilt et al. fandt en anden konsekvens af partikelpartikelsammenlægning i deres undersøgelse af magnettermisk opvarmning og farveforringelse23. Ved lidt højere partikelkoncentrationer eller øget eksponeringstid for marken blev materialernes effektivitet reduceret som materialer, der blev samlet over tid, og de aktive partikeloverfladeområder faldt. Disse og andre anvendelser ville drage fordel af klyngeoverflader designet til at givesteriske barrierer, der udelukkede partikel-partikel interaktioner24,25.
Her rapporterer vi en syntetisk tilgang til at syntetisere mangan ferrit klynger (MFC’ er) med kontrollerbare dimensioner og sammensætning. Disse multidomain partikler består af en samling af primære mangan ferrit nanokrystaller, der er hårdt aggregeret; den tætte tilknytning af de primære nanokrystaller forbedrer deres magnetiske egenskaber og giver en samlet klyngestørrelse, 50-300 nm, godt matchet til de optimale dimensioner for en nanomedicin. Ved at ændre mængden af vand og manganchloridprækursor kan vi selvstændigt kontrollere den samlede diameter og sammensætning. Metoden udnytter enkle og effektive one-pot hydrotermiske reaktioner, der giver mulighed for hyppige eksperimenter og materialeoptimering. Disse MFC’er kan let renses til en koncentreret produktopløsning, som yderligere modificeres af sulfonerede polymerer, der giver kolloid stabilitet. Deres tunability, ensartethed og løsningsfasestabilitet er alle funktioner af stor værdi i anvendelser af nanomaterialer i biomedicinsk og miljømæssig teknik.
Protocol
Representative Results
Discussion
Dette arbejde demonstrerer en modificeret polyolsyntese af mangan ferrit nanokrystaller grupperet sammen i ensartet nanoskala aggregater29. I denne syntese gennemgår jern(III) chlorid og mangan(II) chlorid en tvungen hydrolysereaktion og -reduktion, der danner molekylær MnxFe3-xO4. Disse ferritmolekyler danner primære nanokrystaller under den høje temperatur og højtryk i reaktorerne og samles i i sidste ende i sfæriske aggregater, der her kaldes ma…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
Dette arbejde blev generøst støttet af Brown University og Advanced Energy Consortium. Vi takker taknemmeligt Dr. Qingbo Zhang for hans etablerede syntetiske metode til jernoxid MFC’er.
Materials
| 0.1 Micron Vaccum Filtration Filter | Thermo Fisher Scientific | NC9902431 | for filtration of aggregated clusters after synthesis and surface coating to achieve a uniform solution |
| 2-Acrylamido-2-methylpropane sulfonic acid (AMPS, 99%) | Sigma-Aldrich | 282731-250G | reagent used in copolymer to surface coat nanoclusters and functionalize them for biological media |
| 2,2′-Azobis(2-methylpropionitrile) (AIBN) | Sigma-Aldrich | 441090-100G | reagent used in copolymer making as the free ridical generator |
| 4-Morpholineethanesulfonic acid, 2-(N-Morpholino)ethanesulfonic acid (MES) | Sigma-Aldrich | M3671-250G | acidic buffer used to stabilize nanocluster surface coating process |
| Acrylic acid | Sigma-Aldrich | 147230-100G | reagent used in copolymer to surface coat nanoclusters and functionalize them for biological media; anhydrous, contains 200 ppm MEHQ as inhibitor, 99% |
| Analytical Balance | Avantor | VWR-205AC | used to weigh out solid chemical reagents for use in synthesis and dilution |
| Digital Sonifier and Probe | Branson | B450 | used to sonicate nanocluster solution during surface coating to break up aggregates |
| Dopamine hydrochloride | Sigma-Aldrich | H8502-25G | used in surface coating for ligand exchange reaction |
| Ethylene glycol (anhydrous, 99.8%) | Sigma-Aldrich | 324558-2L | reagent used as solvent in hydrothermal synthesis of nanoclusters |
| Glass Vials (20mL) | Premium Vials | B1015 | container for nanocluster solution during washing and surface coating as well as polymer solutions |
| Graduated Beaker (100mL) | Corning | 1000-100 | container for mixing of solid and liquid reagents during hydrothermal synthesis (to be transferred into autoclave reactor before oven) |
| Handheld Magnet | MSC Industrial Supply, Inc. | 92673904 | 1/2" Long x 1/2" Wide x 1/8" High, 5 Poles, Rectangular Neodymium Magnet low strength magnet used to precipitate nanoclusters from solution (field strength is increased with steel wool when needed) |
| Hydrochloric acid (ACS grade, 37%) | Fisher Scientific | 7647-01-0 | for removing leftover nanocluster debris and cleaning autoclave reactors for next use |
| Hydrothermal Autoclave Reactor | Toption | TOPT-HP500 | container for finished reagent mixture to withstand high temperature and pressure created by the oven in hydrothermal synthesis |
| Iron(III) Chloride Hexahydrate (FeCl3·6H2O, ACS reagent, 97%) | ACS | 236489-500G | reagent used in synthesis of nanoclusters as source of iron (III) that becomes iron (II) in finished nanocluster product (keep dry and weigh out quickly to avoid water contamination) |
| Labware Washer Brushes | Fisher Scientific | 13-641-708 | used to wash and clean glassware before synthesis |
| Magnetic Stir Plate | Thermo Fisher Scientific | 50093538 | for mixing of solid and liquid reagents during hydrothermal synthesis |
| Manganese chloride tetrahydrate (MnCl2·4H2O, 99.0%, crystals, ACS) | Sigma-Aldrich | 1375127-2G | reagent used in synthesis of nanoclusters as source of manganese |
| Micropipette (100-1000μL) | Thermo Fisher Scientific | FF-1000 | for transferring liquid reagents such as water and manganese chloride |
| N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) | Sigma-Aldrich | 25952-53-8 | used in surface coating to assist in ligand exchange of copolymer (keep bulk chemical in freezer and diluted solution in refrigerator) |
| N,N-Dimethylformamide (DMF) | Sigma-Aldrich | 227056-2L | reagent used in copolymer making as the solvent |
| Polyacrylic acid sodium salt (PAA, Mw~6,000) | PolyScience Inc. | 06567-250 | reagent used in hydrothermal synthesis to initially coat the nanoclusters (eventually replaced in surface coating step) |
| Poly(ethylene glycol) methyl ether acrylate | Sigma-Aldrich | 454990-250ML | reagent used in copolymer to surface coat nanoclusters and functionalize them for biological media; average Mn 480, contains 100 ppm BHT as inhibitor, 100 ppm MEHQ as inhibitor |
| Reagents Acetone, 4L, ACS Reagent | Cole-Parmer | UX-78920-66 | used as solvent to precipitate nanoclusters during washing |
| Single Channel Pipette, Adjustable 1-10 mL | Eppendorf | 3123000080 | for transferring ethylene glycol and other liquids |
| Steel Wool | Lowe's | 788470 | used to increase the magnetic field strength in the vial to aid in precipitation of nanoclusters for washing and surface coating |
| Stirring Bar | Thomas Scientific | 8608S92 | for mixing of solid and liquid reagents during hydrothermal synthesis |
| Table Clamp | Grainger | 29YW53 | for tight sealing of autoclave reactor to withstand high pressure of oven during hyrothermal synthesis |
| Urea (ACS reagent, 99.0%) | Sigma-Aldrich | U5128-500G | reagent used in hydrothermal synthesis to create a basic solution |
| Vaccum Filtration Bottle Tops | Thermo Fisher Scientific | 596-3320 | for filtration of aggregated clusters after synthesis and surface coating to achieve a uniform solution |
| Vacuum Controller V-850 | Buchi | BU-V850 | for filtration of aggregated clusters after synthesis and surface coating to achieve a uniform solution |
| Vacuum Oven | Fisher Scientific | 13-262-51 | used to create high temperature and pressure needed for nanocluster formation in hydrothermal synthesis |
Riferimenti
- Makridis, A., et al. In vitro application of Mn-ferrite nanoparticles as novel magnetic hyperthermia agents. Journal of Materials Chemistry B. 2 (47), 8390-8398 (2014).
- Nelson-Cheeseman, B., Chopdekar, R., Toney, M., Arenholz, E., Suzuki, Y. Interplay between magnetism and chemical structure at spinel-spinel interfaces. Journal of Applied Physics. 111 (9), 093903 (2012).
- Otero-Lorenzo, R., Fantechi, E., Sangregorio, C., Salgueiriño, V. Solvothermally driven Mn doping and clustering of iron oxide nanoparticles for heat delivery applications. Chemistry-A European Journal. 22 (19), 6666-6675 (2016).
- Mohapatra, J., et al. Enhancement of magnetic heating efficiency in size controlled MFe 2 O 4 (M= Mn, Fe, Co and Ni) nanoassemblies. Rsc Advances. 5 (19), 14311-14321 (2015).
- Qi, Y., et al. Carboxylic silane-exchanged manganese ferrite nanoclusters with high relaxivity for magnetic resonance imaging. Journal of Materials Chemistry B. 1 (13), 1846-1851 (2013).
- Anandhi, J. S., Jacob, G. A., Joseyphus, R. J. Factors affecting the heating efficiency of Mn-doped Fe3O4 nanoparticles. Journal of Magnetism and Magnetic Materials. 512, 166992 (2020).
- Del Bianco, L., et al. Mechanism of magnetic heating in Mn-doped magnetite nanoparticles and the role of intertwined structural and magnetic properties. Nanoscale. 11 (22), 10896-10910 (2019).
- Padmapriya, G., Manikandan, A., Krishnasamy, V., Jaganathan, S. K., Antony, S. A. Enhanced catalytic activity and magnetic properties of spinel Mn x Zn 1−x Fe 2 O 4 (0.0≤x≤1.0) nano-photocatalysts by microwave irradiation route. Journal of Superconductivity and Novel Magnetism. 29 (8), 2141-2149 (2016).
- Kim, J., et al. Continuous O2-evolving MnFe2O4 nanoparticle-anchored mesoporous silica nanoparticles for efficient photodynamic therapy in hypoxic cancer. Journal of the American Chemical Society. 139 (32), 10992-10995 (2017).
- Silva, L. H., Cruz, F. F., Morales, M. M., Weiss, D. J., Rocco, P. R. Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells. Stem Cell Research & Therapy. 8 (1), 1-8 (2017).
- Otero-Lorenzo, R., Ramos-Docampo, M. A., Rodriguez-Gonzalez, B., Comesaña-Hermo, M., Salgueiriño, V. Solvothermal clustering of magnetic spinel ferrite nanocrystals: a Raman perspective. Chemistry of Materials. 29 (20), 8729-8736 (2017).
- Aghazadeh, M., Karimzadeh, I., Ganjali, M. R. PVP capped Mn2+ doped Fe3O4 nanoparticles: a novel preparation method, surface engineering and characterization. Materials Letters. 228, 137-140 (2018).
- Li, Z., et al. Solvothermal synthesis of MnFe 2 O 4 colloidal nanocrystal assemblies and their magnetic and electrocatalytic properties. New Journal of Chemistry. 39 (1), 361-368 (2015).
- Guo, P., Zhang, G., Yu, J., Li, H., Zhao, X. Controlled synthesis, magnetic and photocatalytic properties of hollow spheres and colloidal nanocrystal clusters of manganese ferrite. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 395, 168-174 (2012).
- Pardo, A., et al. Synthesis, characterization, and evaluation of superparamagnetic doped ferrites as potential therapeutic nanotools. Chemistry of Materials. 32 (6), 2220-2231 (2020).
- Xiao, Z., et al. Libraries of uniform magnetic multicore nanoparticles with tunable dimensions for biomedical and photonic applications. ACS Applied Materials & Interfaces. 12 (37), 41932-41941 (2020).
- Choi, Y. S., Young Yoon, H., Sung Lee, J., Hua Wu, J., Keun Kim, Y. Synthesis and magnetic properties of size-tunable Mn x Fe3−x O4 ferrite nanoclusters. Journal of Applied Physics. 115 (17), (2014).
- Creixell, M., et al. The effect of grafting method on the colloidal stability and in vitro cytotoxicity of carboxymethyl dextran coated magnetic nanoparticles. Journal of Materials Chemistry. 20 (39), 8539-8547 (2010).
- Latorre, M., Rinaldi, C. Applications of magnetic nanoparticles in medicine: magnetic fluid hyperthermia. Puerto Rico Health Sciences Journal. 28 (3), (2009).
- Yeap, S. P., Lim, J., Ooi, B. S., Ahmad, A. L. Agglomeration, colloidal stability, and magnetic separation of magnetic nanoparticles: collective influences on environmental engineering applications. Journal of Nanoparticle Research. 19 (11), 1-15 (2017).
- Lee, S. -. Y., Harris, M. T. Surface modification of magnetic nanoparticles capped by oleic acids: Characterization and colloidal stability in polar solvents. Journal of Colloid and Interface Science. 293 (2), 401-408 (2006).
- Yeap, S. P., Ahmad, A. L., Ooi, B. S., Lim, J. Electrosteric stabilization and its role in cooperative magnetophoresis of colloidal magnetic nanoparticles. Langmuir. 28 (42), 14878-14891 (2012).
- Wydra, R. J., Oliver, C. E., Anderson, K. W., Dziubla, T. D., Hilt, J. Z. Accelerated generation of free radicals by iron oxide nanoparticles in the presence of an alternating magnetic field. RSC Advances. 5 (24), 18888-18893 (2015).
- Bagaria, H. G., et al. Iron oxide nanoparticles grafted with sulfonated copolymers are stable in concentrated brine at elevated temperatures and weakly adsorb on silica. ACS Applied Materials & Interfaces. 5 (8), 3329-3339 (2013).
- Park, J. C., Park, T. Y., Cha, H. J., Seo, J. H. Multifunctional nanocomposite clusters enabled by amphiphilic/bioactive natural polysaccharides. Chemical Engineering Journal. 379, 122406 (2020).
- Hemery, G., et al. Tuning sizes, morphologies, and magnetic properties of monocore versus multicore iron oxide nanoparticles through the controlled addition of water in the polyol synthesis. Inorganic Chemistry. 56 (14), 8232-8243 (2017).
- Lartigue, L., et al. Cooperative organization in iron oxide multi-core nanoparticles potentiates their efficiency as heating mediators and MRI contrast agents. ACS Nano. 6 (12), 10935-10949 (2012).
- Yavayo, C. T., et al. Low-field magnetic separation of monodisperse Fe3O4 nanocrystals. Science. 314 (5801), 964-967 (2006).
- Matijević, E., Scheiner, P. Ferric hydrous oxide sols: III. Preparation of uniform particles by hydrolysis of Fe (III)-chloride,-nitrate, and-perchlorate solutions. Journal of Colloid and Interface Science. 63 (3), 509-524 (1978).
- Weizenecker, J., Gleich, B., Rahmer, J., Dahnke, H., Borgert, J. Three-dimensional real-time in vivo magnetic particle imaging. Physics in Medicine & Biology. 54 (5), 1 (2009).
- Zhu, X., Li, J., Peng, P., Hosseini Nassab, N., Smith, B. R. Quantitative drug release monitoring in tumors of living subjects by magnetic particle imaging nanocomposite. Nano Letters. 19 (10), 6725-6733 (2019).
- Tay, Z. W., et al. Magnetic particle imaging-guided heating in vivo using gradient fields for arbitrary localization of magnetic hyperthermia therapy. ACS Nano. 12 (4), 3699-3713 (2018).
