Targeting drug-delivery systems (DDS) in the formof functionalized nanoparticles has been intensivelyexplored especially for tumor diagnostics and thera-peutics [1–4]. This drug delivery method is attractive,because the substances are easily administered andtransported to the target under certain conditions,al-lowing a safer and more effective tissue-specific re-lease of drugs [5]. However, not every substance canbe used as DDS. There are several conditions thatmust be satisfied so that the nanoparticles could beused to deliver drugs. These comprise among others:small size, the ability to carry a wide variety ofchemotherapeutic agents with sufficient drug space tomeet the desired amount of biologically active drugs,the ability to release the drug at a predictable rate,
*biocompatibility, minimal antigenic properties, bio -degradability , minimized toxicity of the breakdownproducts [6]. Liposomes, polysaccharides, nanocrys-tals, dendrimers, and polymeric, inorganic and modi-fied nanoparticles meet all of these conditions [7–16].Magnetic nanoparticles could be potentially used fordrug delivery, as they can be easily handled by an ex-ternal magnetic field and are preferentially taken upby the target tissue. They also offer the possibility ofbeing used in magnetic resonance imaging (MRI) [17,18]. However, in most of the cases where magneticnanocarriers have been used, difficulties in achievingthe above mentioned objectives appeared. However,it seems that the main factor determining the possi-bility of using nanoparticles as DDS is the strengthof their magnetic force, which must be sufficient to
Corresponding author, e-mail:abuk@prz.edu.pl© BME-PT2
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overcome the force of blood flow and to accumulatedrugs only at target site [19]. Depending on theirmagnetic properties, nanoparticles can be dividedinto pure metals, their alloys and oxides [20–23].Iron oxide nanoparticles, due to the favorable fea-tures they exhibit, are the only type of magnetic nano -particles approved for clinical use by Food and DrugAdministration. Unique properties of Fe3O4 nanopar-ticles, e.g. superparamagnetism, a large surface-to-volume ratio, high surface area, low toxicity, easi-ness of modification, offer enormous potential in thefields of immobilization of biomaterials [24–27],bioseparation [26–31] and bioengineering usage [32–36].Moreover, the most important fact is the naturaloccurrence of iron oxides in human heart, spleen andliver [37], what implies their biocompatibility andnon-toxicity at a physiological concentration.
Since the pure Fe3O4nanoparticles often have poorstability and dispersion, various modification meth-ods have been exploited to obtain soluble and bio-compatible Fe3O4nanoparticles. The resulting mod-ified Fe3O4nanoparticles have been extensively usedfor various applications. However, it is of crucial im-portance that the materials used for modification arenon-toxic. The aim of this study was to verify, whichsynthesis procedure allows obtaining surface modi-fied Fe3O4nanoparticles with a size below 100nm.This biocompatible nanocomposite (NC) could findpotential application as DDS. For this purpose, thesurface of the synthesized Fe3O4nanoparticles wasmodified by two functionalization methods: seed –emulsion and distillation – precipitation polymeriza-tion. The global information on the composites wasobtained by DLS as well as FTIR and UV-Vis spec-troscopy. The combination of TEM imaging withEDS chemical mapping allowed to detect the core-shell structure of the synthesized composites and geo-metrically locate the respective elements present inthe material. A variety of potential applications as wellas limitations of the functionalized Fe3O4nanocom-posite particles were discussed.
extraction with an aqueous solution of 5% NaOHand 20% NaCl. Initiators (2,2′-azobis(2-methylpro-pionitrile), AIBN, 98%, China and potassium per-sulfate, KPS, >99%, Germany) were purchased fromSigma-Aldrich and used as purchased. Other chem-icals, sodium citrate bihydrate (POCh, Poland), 3-(trimethoxysilyl)propyl methacrylate (98%, Aldrich,China), iron(II) sulfate tetrahydrate (Sigma-Aldrich,India), iron(III) chloride hexahydrate (CHEMPUR,Poland), ammonia solution (28wt%, POCh, Poland),and organic solvents (acetonitrile, ethanol, POCh,Poland) were also used as purchased.
2.2. Synthesis of citrate stabilized Fe3O4
particles
The synthesis of the Fe3O4nanoparticles was per-formed in a glass reactor (100ml) equipped with aheating coat, a mechanical stirrer, a condenser, a drop-ping funnel and a source of argon. The reactor wasconnected to a thermostat and immersed additionallyin an ultrasonic bath. FeCl3·6H2O (5mmol) andFeSO4·4H2O (2.5mmol) were dissolved in deion-ized water (15mL). The resulting solution was heat-ed to 70°C and ammonia solution (4mL, 28wt%was added dropwise. After 30minutes, a solution ofsodium citrate (2mmol, 0.5g/mL) was added to sta-bilize the precipitated black colored nanoparticles ofFe3O4. Next, the reaction temperature was raised to90°C and the reaction was continued with simulta-neous sonication of the mixture constantly for 60min-utes. The resulting magnetite particles were separat-ed from the solution by using a strong magnet. Theywere then rinsed many times with deionized water.The magnetic properties were also used to isolate theparticles at this stage. The final product was kept dis-persed in water (10mL).
2.3. Modification of magnetite particles
The modification was performed in the same glassreactor (100mL) equipped as described above.Ethanol (30mL), 3-(trimethoxysilyl)propyl methacry-late (0.95mL, 4mmol), and ammonia (2mL of25wt% solution) were added to the water dispersionof the Fe3O4particles obtained in the previous step.The mixture was heated in the reactor to 70°C andmixed for 24hours. The resulting product of asilanization reaction, Fe3O4@MPS, being in the formof bright brown particles, was rinsed with water and
2. Experimental
2.1. Materials and chemicals
Divinylbenzene (DVB, 80%, Aldrich, Germany), gly-cidyl methacrylate (GMA, >97%, Aldrich, Germany)and styrene (S, >99%, Fluka, Switzerland) were usedas monomers. They were purified from inhibitors by
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Figure 1.Synthesis and modification of Fe3O4NPs to obtain
Fe3O4@MPS
ethanol, by decantation using a strong magnet, anddried under reduced pressure. This methodology ap-plied previously by Xu et al. [38] allowed obtainingnanoparticles capable to copolymerize with other un-saturated monomers. The scheme of synthesis andmodification of Fe3O4nanoparticles is presented inFigure1.
Figure 2.Simplified scheme of syntheses of two types of
Fe3O4-polymer composite particles: Fe3O4@ MPS@GMA-S-DVB (methodI, right side); Fe3O4@MPS@DVB-GMA (method II, left side)
2.4. Synthesis of functionalized composite
particles
2.4.1. MethodI – seed emulsion polymerizationFor a typical polymerization procedure, Fe3O4@MPSparticles (40mg) were placed in a 100mL glass re-actor, equipped with a mechanical stirrer and asource of argon, and dispersed in demineralized water(50mL). The dispersion was sonicated for 30min-utes. After that time, styrene (0.208g, 2mmol) wasadded to the mixture and the sonication was contin-ued for further 30minutes. Next, the reaction mix-ture was heated to 80°C and a water solution of potas-sium persulfate (0.6mL, 10mg/g) was added. Afternext 1hour, divinylbenzene (0.029g, 0.22mmol) andglycidyl methacrylate (0.079g, 0.55mmol) wereadded to the mixture. The polymerization was con-tinued for 16hours at 90°C. The final product,Fe3O4@MPS@GMA-S-DVB, was rinsed with waterand ethanol, by decantation using a strong magnet,and dried under reduced pressure.
2.4.2. MethodII – distillation – precipitation
polymerization
Distillation – precipitation polymerization was per-formed in three-neck flask equipped with a mechan-ical stirrer, a Dean Stark apparatus and a source ofargon. The conditions of the polymerization weresimilar to those applied in [39]. For a typical polymer-ization procedure, Fe3O4@MPS dispersion in ace-tonitrile (40mg/80mL) was sonicated for 30min-utes using an ultrasonic bath and a mixture of glycidyl
methacrylate (1.92g, 13.5mmol), divinylbenzene(0.19g, 1.5mmol) and AIBN (40mg) was added. Thepolymerization was carried out in the boiling stateof the reaction mixture for 2hours, until distillingabout 50% of acetonitrile. The resulting particles(Fe3O4@MPS@DVB-GMA) were rinsed with a1:1v/v mixture of ethanol and acetonitrile, by de-cantation using a strong magnet, and dried under re-duced pressure.
The simplified scheme of syntheses of Fe3O4-poly-mer composite particles using methodI and methodIIis presented in Figure2.
2.5. Characterization of Fe3O4and modified
magnetic particles
2.5.1. Particle size measurements
Dynamic Light Scattering (DLS) technique was usedto assess particle size distribution. The measurementswere performed at 20°C using a Zetasizer Nano ZSinstrument from Malvern with a red laser (633nm,He-Ne, 4,0mW). The measurement angle was set at173° (Backscatter NIBS default).
2.5.2. TEM
The structure of the synthesized Fe3O4modified par-ticles (Fe3O4@MPS), the composite particles ob-tained using seed emulsion polymerization (Fe3O4@MPS@GMA-S-DVB) and distillation – precipita-tion polymerization methods (Fe3O4@MPS@DVB-GMA) were analyzed by transmission electron mi-croscopy (TEM). A drop of each suspension was de-posited on a TEM Cu grid coated with a carbon foil,and subsequently dried. The sample was observed inthe scanning transmission electron microscopy(STEM) mode using the high angular annular darkfield (HAADF) detector on a FEI Tecnai Osiris op-erating at 200kV with resolution of 0.15nm inSTEM. The chemical analysis of the samples was
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performed by energy dispersive spectroscopy usingSuper EDX.
2.5.3 Infrared spectroscopy measurements
FTIR spectra were recorded using a Thermo Scien-tific Nicolet 8700 spectrometer and the KBr pelletmethod or an FTIR Nicolet iN10 MX microscope inthe reflectance mode. All the analyses were per-formed in the mid IR range, more precisely between400–4000cm–1wavelength. or 128scans wereused to obtain the spectral resolution of 0.1cm–1.2.5.4. UV-Vis
Diffuse reflectance UV-Vis spectra were recordedusing a Jasco V-670 spectrophotometer equipped witha Jasco ISN-723 UV-Vis NIR 60mm integratingsphere. BaSO4was used as a standard. The resolu-tion was chosen to be 1 nm and the scan speed was1000nm/min. The spectral range was from 190nmto 800nm.
2.5.5. TGA analysis
TGA analyses were performed using a METTLERTOLEDO TGA/DSC 1 analyzer. Samples (2–2.5mg)were heated from 25 to 800°C (10°C/min) under ni-trogen atmosphere (50mLN2/min).
the DLS measurements. Their results are shown inFigure3. The Fe3O4@MPS particles had an averagesize of 40nm and relatively low size dispersion. Thismade them interesting as potential seeds for emulsionand distillation-precipitation polymerization func-tionalization. The peaks with maxima at approxi-mately 100nm size were observed for composite par-ticles functionalized by seed emulsion polymeriza-tion (Fe3O4@MPS@GMA-S-DVB) and distillation– precipitation polymerization (Fe3O4@MPS@GMA-DVB) methods. However, in these cases the disper-sion of the particle size was clearly larger.
3. Results
3.1. Particle size distribution
The first information about the size distribution ofthe synthesized particle particles was obtained from
Figure 3.DLS spectrum of size distribution observed for
Fe3O4@MPS(·····), Fe3O4@MPS@GMA-DVB(), Fe3O4@MPS@GMA-S-DVB(–––)nanoparticles
3.2. Structural characterization
The general morphology of the seed emulsion poly-merization produced Fe3O4@MPS@GMA-S-DVBNPs is presented in the HAADF STEM image Fig-ure4a. The aim of the synthesis was to obtain nano -composite particles consisting of a Fe3O4core sur-rounded by a polymer shell. From Figure4a can beclearly seen, that the synthesis of the nanocompositeparticles was successful, when seed emulsion poly-merization was applied. The particles are intercon-nected by their shells, forming long chains. However,the agglomeration effect observed in STEM HAADFimage (Figure4a) could result from the magnetic in-teractions between nanoparticles and not from anycovalent chemical connection between the polymershells. The majority of Fe3O4@MPS@GMA-S-DVBNPs has a core-shell structure as shown in Figure4b.Some of the NC particles contain more than oneFe3O4@MPS nanoparticles. Nevertheless, most of theparticles have a size around 100nm, which is con-sistent with the result obtained by DLS. However,smaller, agglomerated Fe3O4@MPS NPs, Figure4c,and larger NC nanoparticles, which are surroundedby numerous Fe3O4@MPS NPs, Figure4d, can befound in the sample.
The STEM HAADF imaging, Figure5a, revealed thatthe sample of the nanocomposite particles obtainedusing distillation-precipitation polymerization con-sists of large, perfectly spherical particles with diam-eters varying from about 500nm to over 2µm.The white contrasted shell on the spherical particlesin Figure5a, stems from the presence of smaller par-ticles agglomerated on their surface. This observa-tion is indeed confirmed by the EDS chemical map-ping, Figure5. Indeed, in the EDS elemental map
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Figure 4.STEM HAADF images of the Fe3O4@MPS@GMA-S-DVB nanoparticles synthesized by seed emulsion polymer-ization: (a)overview image; (b)individual nanoparticle with a clearly visible Fe3O4@MPS core surrounded by apolymer shell; (c)magnified view of agglomerated Fe3O4@MPS NPs; (d)polymer nanoparticle surrounded byFe3O4@MPS NPs
Figure 5.Chemical mapping by EDS of the Fe3O4@MPS@GMA-DVB particles: (a)STEM HAADF image with the corre-sponding maps: (b)Fe; (c)O; (d)Si; (e)collective map of O, Fe and Si
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Figure 6.Detailed chemical mapping of the Fe3O4@MPS@GMA-DVB nanoparticle shell: (a)STEM HAADF image;
(b)magnified view of the Fe3O4particles forming the shell; the corresponding EDS maps: (c)Fe; (d)Si; (e)col-lective map of O, Fe and Si
the stronger iron signal is detected on the polymerspheres, Figure5b. Also the oxygen signal is strongeron the circumference of the spheres, Figure5c. Ac-cording to the EDS maps the distribution of Si is uni-form in the polymer spheres, Figure5d.
The agglomeration of the Fe3O4@MPS NPs on thesurface of the GMA-DVB polymer spheres is evenbetter visible on the detailed view of the sphere sur-face in the STEM HAADF image with the correspon-ding EDS maps, Figure6. Individual Fe3O4@MPSNPs are visible on the magnified HAADF image inFigure6b. The Fe signal is clearly stronger on the sur-face of the polymer spheres, Figure6c. The Si signalis detected not only in the polymer core of the spheresbut also at the same location as the Fe signal.
3.3. FTIR and DR UV-Vis analysis
Figure7 shows a comparison of the FTIR spectra col-lected for the four types of samples bearing Fe3O4NPs. The absorption bands present in the FTIR spec-trum of the unmodified particles at 570cm–1corre-
spond to Fe–O–Fe skeletal vibrations in Fe3O4, and3420cm–1can be attributed to the symmetric stretch-ing vibrations of OH groups (the first of the bands).The presence of symmetrical and asymmetric stretch-ing vibrations of COO–groups at 1615 and 1400cm–1strongly suggests that indeed citrate coated mag-netite particles were obtained (Figure7a) [40]. Thesynthesized Fe3O4particles were subsequently treat-ed with 3-(trimethoxysilyl)propyl methacrylate to at-tach methacrylate groups on the surface of magnetitenanoparticles. The success of magnetite modificationunder the applied conditions was proved by a FTIRspectrum presented in Figure7b. The strong absorp-tion bands found in the spectrum of the modifiedparticles at 1750cm–1are attributed to ester carbonylgroups. The bands at 1263 and 1128cm–1correspondto the stretching vibrations of C–O–C and/or Si–O–Siskeletal vibrations. Thus it seems that the attachmentof methacrylate moieties on the surface of Fe3O4particles was successful [41]. The FTIR spectrum ofthe particles synthesized using the emulsion poly-
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merization method is shown in Figure7c. The bandsattributed to styrene, divinylbenzene and glycidylmethacrylate were found as dominant peaks in thecollected spectrum. The bands observed in the rangeof 2850–3050cm–1confirm the presence of aliphaticand aromatic hydrocarbon groups, respectively. Theabsorption band at ~1720cm–1corresponds to theester carbonyl group stretching vibrations. The bandsat 1050 and 1250cm–1can be assigned to the asym-metric and symmetric C–O–C skeletal vibrations andthose at 750–800cm–1, observed in the range char-acteristic of the epoxy ring stretchings, indicate thepresence of glycidyl methacrylate mers in the syn-thesized polymer particles. The FTIR spectrum (Fig-ure7d), which is registered for the product of distil-lation – precipitation polymerization, is dominated bybands related to the presence of repeating units ofGMA and DVB. Absorption bands corresponding tothe vibrations of the hydrocarbyl groups (2850– 3050,1600, 1490 and 1450cm–1), ester carbonyl groups(1720cm–1), C–O–C moieties (approx. 1100cm–1)and epoxy groups (900–840cm–1) are observed in thespectrum. Due to the low percentage of the modifiedmagnetite particles, a smaller absorption in the range
Figure 8.DR UV-Vis spectra recorded for the synthesized
particles: Fe3O4@MPS(···), Fe3O4@MPS@GMA-S-DVB(), Fe3O4@MPS@GMA-DVB(–––)
typical for magnetite (from approx. 570cm–1) is ob-served [42, 43].
To determine the optical properties of the modifiedand functionalized Fe3O4nanoparticles the DR UV-Vis spectra were collected. They are shown in Fig-ure8. For the Fe3O4@MPS NPs the maximum ab-sorption at about 320 nm was found, which corre-sponds to previously published data [44]. It was shift-ed towards higher wavelength values in the cases offunctionalized Fe3O4nanoparticles, i.e. the red shiftswere observed.
3.4. TGA analysis
Figure9 presents TGA curves obtained for the par-ticles provided by seed emulsion and those preparedby distillation-precipitation polymerization. The sam-ples of the particles were heated slowly up to 800°C.In both cases the relatively slow weight loss was ob-
Figure 7.Typical FTIR spectra of: (a)Fe3O4 nanoparticles
(KBr), (b)Fe3O4@MPS nanoparticles, (c)Fe3O4@MPS@GMA-S-DVB, (d)Fe3O4@MPS@GMA-DVB
Figure 9.TGA curves of Fe3O4@MPS@GMA-S-DVB(
Fe3O4@MPS@GMA-DVB(···)
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served up to about 300°C. It results from removal ofabsorbed water and/or other solvents used duringpreparation of the particles. Above this temperaturethe rate of decomposition clearly increased andreached the maxima at 415°C for Fe3O4@MPS@GMA-S-DVB and at 390°C for Fe3O4@MPS@GMA-DVB particles. Additionally, in the case ofFe3O4@MPS@GMA-DVB the second, local in-crease in decomposition rate was observed with themaximum at about 740°C.
4. Discussion
Modified and functionalized Fe3O4nanoparticles areincreasingly used as DDS [45–49]. The aim of thisstudy was to functionalize Fe3O4@MPS NPs and ob-tain core-shell nanocomposites with a Fe3O4@MPScore surrounded by the DVB-(S)-GMA polymer shellto make these materials useful for medical applica-tions.
Materials, which are dedicated as DDS, must meetseveral conditions, which were mentioned in the in-troduction. Among others, materials introduced intothe human body, must not be toxic [6]. The modifi-cation and functionalization of the studied nanocom-posites required a selection of the suitable mono -mers. 3-(Trimethoxysilyl)propyl methacrylate – MPS,divinylbenzene – DVB, glycidyl methacrylate – GMA,and styrene – S seem to meet the requirements oflack of toxicity for human body after their polymer-ization.
Another requirement for particles applied as DDS istheir minimal size. Thus, their diameter must be be-tween 2 and 100nm, as smaller nanoparticles wouldpass through the blood-brain barrier [6]. However,drug release is affected by particle size. Smaller par-ticles have larger surface area, therefore, most of thedrug would be at or near the particle surface, leadingto fast drug release. While, larger particles have largecores, which allow more drug to be encapsulated andslowly diffuse out. Smaller particles also have ten-dency to aggregate during storage and transportationof nanoparticle dispersion.
The results obtained by DLS indicate that the diam-eter of the Fe3O4@MPS and Fe3O4@MPS@GMA-S-DVB (particles obtained using seed emulsion poly-merization) is within the range from 2–100nm. Thepresence of the nano-sized particles was also detect-ed by the DLS measurements in the sample of the
particles obtained by distillation-precipitation poly-merization. However, this technique of heteroge-neous polymerization provided larger particles aswell, reaching about 2µm in diameter.
The micro-size of the synthesized particles does notdisqualify them, however, as potential materials fordrug delivery. Such micro-sized particles were stud-ied, for example, by Tao and Desai, who developedmicrofabrication as controlled delivery devices [50].These devices provide the capacity to target cells,promote unidirectional controlled release, and en-hance permeation across the intestinal epithelial bar-rier [50–52]. Another application of microparticlesare biosensors and for size exclusion chromatogra-phy [52, 53].
Much attention has been devoted to optimize surfacecoating of magnetic NPs formulations for their useas DDS [54]. Without an inert coating, Fe3O4NPsare subject to opsonization and rapid clearance fromthe blood by the reticuloendothelial system (RES). Inour case, the formation of polymer – Fe3O4nano-composites was confirmed by FTIR measurements.This is evidenced by the absorbance maxima atwavelengths of the wave numbers of ~1720, 1050,1250, and 750–800cm–1corresponding to the vibra-tions from the mers of glycidyl methacrylate in thesynthesized polymer particles [42, 43]. However,FTIR spectroscopy provided only information aboutthe chemistry of nanocomposites. To verify their mor-phology, STEM analysis, including EDS was per-formed. Scanning transmission electron microscopyimaging allowed observing the shape and size of thesynthesized composite particles. However, STEMenables only visualizing the core and the shell of theparticles, while it is impossible to determine theirchemical composition. Thus EDS mapping was ap-plied, as it is the only technique that allows visual-izing the geometric position of the respective chem-ical elements present in the individual particles.Consequently, information on the location of the el-ements used for functionalization of the compositeswas obtained.
STEM analysis of nanocomposites with Fe3O4syn-thesized using the seed emulsion polymerization func-tionalization method confirmed that the core-shellstructure was indeed achieved. The nanocompositeswere composed of a Fe3O4@MPS core surrounded bya polymer shell. The functionalization prevented the
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100nm polymer nanocomposites from agglomera-tion.
On the contrary, the distillation – precipitation poly-merization method resulted in nanocomposite parti-cles consisting of Fe3O4@MPS NPs immersed en-tirely in a bulk polymer core. Additionally, the par-ticles are surrounded by a Fe3O4@MPS shell, as wasclearly shown by STEM and EDS analysis. Indeed,the Si signal is not only detected in the polymer coreof the composite spheres but also in the same loca-tion as the Fe signal, confirming the presence of theMPS shell around the Fe3O4cores. The presence ofthe MPS shell around the Fe3O4NPs was also con-firmed by FTIR. After subtracting the spectrum col-lected for pure Fe3O4NPs using the OPUS softwarefrom the spectrum of Fe3O4@MPS particles no peakcorresponding to pure Fe3O4was visible.
STEM imaging of the Fe3O4@MPS nanocompos-ites functionalized by the seed emulsion polymeriza-tion method showed a relatively uniform size of theNC particles, around 100nm, confirmed by DLS
-measurements. In the case of the Fe3O4@MPS nano composites functionalized by the distillation – pre-cipitation polymerization method, the detailed STEManalysis showed a very large particle size distribu-tion, both nano- and micro-sized particles. The micro-sized particles are perfectly spherical and reach sizesup to around 2µm. The large size distribution makesthem rather unsuitable as DDS.
An important prerequisite is that nanoparticles forDDS applications should not be agglomerated. Thisis one of the principal problems for researchers syn-thesizing nanoparticles. The STEM images of theFe3O4@MPS@GMA-S-DVB nanocomposites clear-lyshow that the functionalization by the seed emul-sion polymerization method prevented the 100nmnanocomposite particles from agglomeration. Con-versely, the surface of Fe3O4@MPS@DVB-GMAspheres was coated by Fe3O4@MPS NPs, what showsthat MPS modification only, does not prevent theFe3O4NPs from agglomeration.
Fe3O4introduced into the structure of the polymerparticles maintains magnetic properties, useful, forexample for separation of the catalyst or sorption ap-plications, controlled delivery of drugs or medicalimaging [53, 55–57]. The size of iron oxide cores isan important parameter that affects the magneticproperties of NPs [49, 58]. The magnetic properties
of the synthesized nanoparticles can be applied inmagnetic resonance imaging (MRI) [17]. Moreover,they can be used as DDS for antibiotics [59], anti-cancer drugs [60], neurotransmitters [61]. Further-more, the presence of modifiable functional groupsfacilitates the attachment of different therapeuticagents.
Considering the obtained results, as well as the lit-erature data, it is clearly visible that the modified andfunctionalized Fe3O4nanoparticles could be poten-tially used like DDS. The spectroscopic measure-ments allowed for identifying the introduced chem-ical changes into Fe3O4@MPS nanoparticles func-tionalized by two different methods. However, theTEM imaging has shown that only the seed emulsionpolymerization functionalization method of Fe3O4@MPS nanoparticles was successful, resulting in theaimed nanocomposite structure consisting of a Fe3O4@MPS core and a polymer shell.
TGA analyses of the particles showed that the totalweight loss of Fe3O4@MPS@GMA-S-DVB parti-cles was only about 50%. This finding can be addi-tional proof of the core-shell nature of the particlesprovided by seed emulsion polymerization (MethodI).In the case of Fe3O4@MPS@GMA-DVB particlesthe total weight loss of the analyzed sample amountedto about 90%. It proves that the particles synthesizedby method II (precipitation – distillation polymer-ization) has mainly of organic nature, i.e. the inor-ganic particles are immersed in the polymer bulk.
5. Conclusions
The present study describes the synthesis, modifica-tion and functionalization of Fe3O4nanoparticles.Two different functionalization methods of the Fe3O4@MPS nanoparticles were investigated: seed - emul-sion and distillation – precipitation polymerization.FTIR spectroscopy showed that in both cases a poly-mer – Fe3O4nanocomposite was obtained and thepolymer chains had been effectively grafted onto thesurface of Fe3O4@MPS nanoparticles. As biocom-patible polymers were used for the functionalizationof the Fe3O4@MPS nanoparticles, the resulting prod-uct could be applied potentially as DDS. However,morphological analysis by TEM showed that only theseed emulsion polymerization method resulted in aFe3O4@MPS core/polymer shell structure of thenanoparticles. DLS and TEM measurements con-
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firmed that their size was mainly in the range of100nm. The polymer shell prevented the NPs fromagglomeration. In the case of the distillation – precip-itation polymerization method the large, perfectlyspherical nanocomposite particles coated by Fe3O4@MPS NPs were mainly obtained. However, the TEMinvestigation, supported by DLS measurements,showed that these polymer core composite sphereshad size varying from nanometers to over 2µm.
[9]Šubr V., Ulbrich K.: Synthesis and properties of newN-(2-hydroxypropyl)methacrylamide copolymers con-taining thiazolidine-2-thione reactive groups. Reactiveand Functional Polymers, 66, 1525–1538 (2006).
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Acknowledgements
The use of the FEI Tecnai Osiris TEM instrument located atthe Center for Innovation and Transfer of Natural Sciencesand Engineering Knowledge of the University of Rzeszowis acknowledged.
[11]Xiong X-B., Mahmud A., Uludaǧ H., Lavasanifar A.:
Conjugation of arginine-glycine-aspartic acid peptidesto poly(ethylene oxide)-b-poly(ε-caprolactone) micellesfor enhanced intracellular drug delivery to metastatictumor cells. Biomacromolecules, 8, 874–884 (2007).
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