Article Cite This: Langmuir XXXX, XXX, XXX−XXX
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Polymeric Nanocomplex Encapsulating Iron Oxide Nanoparticles in Constant Size for Controllable Magnetic Field Reactivity Sang Hun Chun,† Seung Won Shin,† Lunjakorn Amornkitbamrung,† So Yeon Ahn,† Ji Soo Yuk,† Sang Jun Sim,§ Dan Luo,∥ and Soong Ho Um*,†,‡
Langmuir Downloaded from pubs.acs.org by KAOHSIUNG MEDICAL UNIV on 10/15/18. For personal use only.
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School of Chemical Engineering and ‡SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea § Department of Chemical and Biological Engineering, Korea University, Seoul 136-713, South Korea ∥ Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14850, United States S Supporting Information *
ABSTRACT: The magnetic properties of nanoparticles make them ideal for using in various applications, especially in biomedical applications. However, the magnetic force generated by a single nanoparticle is low. Herein, we describe the development of nanocomplexes (size of 100 nm) of many iron oxide nanoparticles (IONPs) encapsulated in poly(lacticco-glycolic acid) (PLGA) using the simple method of emulsion solvent evaporation. The response of the IONPencapsulated PLGA nanocomplexes (IPNs) to an external magnetic field could be controlled by modifying the amount of IONPs loaded into each nanocomplex. In a constant size of IPNs, larger loading numbers of IONPs resulted in more rapid responses to a magnetic field. In addition, nanocomplexes were coated with a silica layer to facilitate the addition of fluorescent dyes. This allowed visualization of the responses of the IPNs to an applied magnetic field corresponding to the IONP loading amount. We envision that these versatile, easy-tofabricate IPNs with controllable magnetism will have important potential applications in diverse fields.
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immediate response to an external magnetic field and showing poor performance in biological applications.10 When a magnetic nanoparticle moves through a flowing solution, a resistance called hydrodynamic drag force is generated. By combining equations corresponding to the forces from magnetic and hydrodynamic drag, the velocity of a nanoparticle can be calculated as follows
INTRODUCTION With the advancement of nanotechnology, several promising biomedical trials have been performed with functional nanomaterials.1−5 Unique characteristics of nanomaterials, such as optical properties of gold nanoparticles and magnetic properties of iron oxide nanoparticles (IONPs), have significant potentials in therapeutics and diagnostics.6−9 The magnetic properties of biocompatible nanomaterials such as iron oxide and nickel oxide have been studied intensively and exploited for various biomedical uses.10 For example, superparamagnetism of nanomaterials facilitates the collection of a variety of target materials from a complex solution, ranging from antibodies to cells or parasites,11−15 and is especially suited for purifying rare entities.16 Superparamagnetic IONPs have also been used for therapeutic applications. The response to the magnetic field of the nanoparticles enables the drug to be effectively delivered to the target site.17,18 In addition, the heat generated from IONPs, while they were exposed to alternating magnetic field, is used for hyperthermal therapy.19 IONP can also be used as a contrast agent for magnetic resonance imaging.20 Although the magnetic properties of nanoparticles have been exploited in several biomedical fields, the magnetic force generated by a single nanoparticle is weak, preventing an © XXXX American Chemical Society
Δυ =
R m 2Δχ ∇ (B 2 ) 9μ0 η
where Δυ is the velocity difference between a magnetic nanoparticle and the medium, Rm is the radius of the nanoparticle, Δχ is the effective magnetic susceptibility of the nanoparticle relative to the medium, μ0 is the permeability of the free space, and η is the viscosity of the medium. B is the magnetic induction defined as B = μ0(H + M), where M is the magnetization of the nanoparticle and H is the magnetic field strength.21 According to the above equation, the response of a nanoparticle can be improved by using a magnetic nanoparticle with a larger magnetic induction (B) and, especially, Received: December 4, 2017 Revised: August 28, 2018
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DOI: 10.1021/acs.langmuir.7b04143 Langmuir XXXX, XXX, XXX−XXX
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Deionized water (18.2 MΩ cm−1), chloroform (99%), and ethanol (99.9%) were used as solvents in various experimental steps. Synthesis of IONPs. Superparamagnetic IONPs were prepared using a thermal decomposition method.26 Briefly, 10.8 g of iron(III) chloride hexahydrate and 36.5 g of sodium oleate were stepwise dissolved in 140 mL of hexane, 80 mL of ethanol, and 60 mL of water. The resulting solution was gently stirred for 4 h at 60 °C and transferred to a separatory funnel, followed by washing with hexane, ethanol, and water. After discarding the bottom phase of water− ethanol, the upper phase solvent, hexane, was removed using a rotary evaporator at 80 °C. A sticky iron oleate solution was obtained and used as a precursor for the synthesis of IONPs. Twelve grams of iron oleate and 1.9 g of oleic acid were dissolved in 66.7 g of 1-octadecene. Then, the mixture was heated to 320 °C at a heating speed of 3.3 °C/ min. The temperature was kept at 320 °C for 30 min, and the mixture was cooled to room temperature. The obtained solution of IONPs was diluted with hexane, followed by precipitation in acetone and ethanol. The precipitated IONPs were finally dispersed in chloroform. Synthesis of Nanocomplexes Composed of PLGA and IONPs. IPNs were prepared by an emulsion solvent evaporation method.27 Briefly, 100 mg of IONPs was added to 2 mL of 10 mg/mL PLGA in the chloroform solution. Then, the mixture was transferred to 4.5 mL of 3% (w/v) PVA aqueous solution. After a 2 min vortex and 2 min sonication at an amplitude of 10%, the color of the solution turned from black to dark brown because of emulsion formation. The emulsified solution was injected dropwise into 20 mL of 1% (w/v) PVA aqueous solution, and the resulting mixture was stirred overnight to allow the organic solvent to evaporate. The obtained IPNs were washed twice by centrifugation (15,000g, 15 min, 20 °C) using water as a solvent and finally redispersed in 25 mL of water. To synthesize IPNs with different loading amounts of IONPs, different volumes (2, 1, 0.5, and 0.25 mL) of chloroform were used to prepare IONP solutions with concentrations of 50, 100, 200, and 400 mg/mL, respectively. The concentration of PLGA was fixed at 10 mg/mL. Synthesis of Silica-Coated Nanocomplexes. IPNs were coated with a silica layer using the general Stöber method. Twenty milliliters of ethanol and 3 mL of water were added to 5 mL of IPN aqueous solution at 800 rpm stirring. Then, 1 mL of 30% ammonium hydroxide aqueous solution and 0.5 mL of TEOS were added dropwise. After 20 min of stirring, silica-coated IPNs were washed several times by centrifugation (15,000g, 15 min, 20 °C) using water as a solvent and finally redispersed in 5 mL of water. Characterization. The size and shape of IONPs, IPNs, and silicacoated IPNs were visualized using a transmission electron microscope (TEM, JEM-2100F, JEOL, Japan) operated at 300 kV and a scanning electron microscope (SEM, JSM-7600F, JEOL, Japan) operated at 15 kV. For TEM analysis, samples were dropped onto a carbon-film covered copper grid (200-mesh pure carbon, Ted Pella Inc., USA). For SEM analysis, samples were dropped onto a silicon wafer and dried at room temperature. The size and size distribution of the IPNs and silica-coated IPNs were measured by using dynamic light scattering (DLS, Zetasizer Nano ZS90, Malvern, UK). For DLS measurement, samples were 10 times diluted with water. Laminated layers of samples were observed using a fluorescence microscope (Axiovert 200M, Zeiss, Germany). Magnetization of silica-coated IPNs was measured using a vibrating sample magnetometer (VSM, MicroSense-EV7, MicroSense, USA). Samples were prepared in a powder form using a lyophilizer (FDU-1200, EYELA, Japan). For the measurement of magnetic response kinetics of IPN and the encapsulated IONPs, a UV−vis spectrometer (SpectraMax M5 Microplate Reader, Molecular Devices, USA) was used. To calculate the amounts of encapsulated IONPs in IPNs prepared with different concentrations of IONPs, IPNs were transferred to chloroform and dissolved with 2 min of sonication at an amplitude of 10%. The absorbances of dissolved IPNs were measured by UV−vis spectroscopy and compared with the previously obtained standard curve of IONPs. After measuring the amounts of encapsulated IONPs, encapsulation efficiency (EE) and loading efficiency (LE) of IONPs per unit complex were calculated.
magnetization of the nanoparticle (M). As a part of the method of increasing the magnetization, relationship between size and magnetization of magnetic nanoparticles or their clusters has been studied previously.22−24 In general, the relationship between the size and magnetization of magnetic nanoparticles is analyzed using a core−shell model that considers the contributions of surface and bulk components. In the model, the relationship is defined as follows 2e y i M = MShl + (MCor − MShl)jjj1 − zzz D{ k
where M is the total magnetization, MShl and MCor are contributions to the magnetization from shell and core, respectively, e is the thickness of the shell, and D is the diameter of the particle.23 According to this equation, magnetic nanoparticles with larger sizes provide higher magnetization, assuming that the contribution from the shell is negligible compared to the contribution at the core. In this aspect, the greater magnetization of larger particles or clusters has been emphasized; therefore, controlling their size to tune their response to a magnetic force will be important for potential, real-world biomedical applications. However, use of iron oxide clusters may require controllable magnetization relying on a proper size range of clusters, especially for biomedical applications. For example, in drug delivery systems that use nanomaterial as a therapeutic agent or a carrier, the size of nanomaterial is a key determinant of the half-life of drug clearance in the tissue. As studied previously, the particle size should be small enough (10 nm) to overcome kidney filtration and rapid penetration.25 To address this issue and provide a universal platform for creating magnetic forcecontrollable systems, we developed nanocomplexes (with a size of 100 nm) of IONPs encapsulated in poly(lactic-co-glycolic acid) (PLGA) using emulsion solvent evaporation. In the oilin-water emulsion phase, oleate-coated IONPs were easily trapped inside the chloroform oil emulsion with PLGA polymers. Through solvent evaporation, IONPs were encapsulated in PLGA nanoparticles. By modifying the loaded amounts of IONPs from 32.4 to 91.4 wt %, the magnetization of IONP-encapsulated PLGA nanocomplexes (IPNs) was controllable from 1.8 to 7.6 emu/g, whereas their size remained constant in approximately 100 nm. Furthermore, nanocomplexes were coated with a silica layer to facilitate surface functionalization. Conjugation of fluorescent dyes to silica-coated IPNs was performed to visually assess the responses of IPNs synthesized with different amounts of IONPs to a magnetic field. It is highly expected that such new magnetic nanocomplexes may be a promising alternative to conventional magnetic nanoparticles.
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EXPERIMENTAL SECTION
Materials. Sodium oleate (CH3(CH2)7CHCH(CH2)7COONa, >97%) was purchased from Tokyo Chemical Industry (TCI, Japan). Iron(III) chloride hexahydrate (FeCl3·6H2O, >97%), oleic acid (CH3(CH2)7CHCH(CH2)7COOH), 1-octadecene (CH3(CH2)15CHCH2, 90%), poly(vinyl alcohol) (PVA, Mw = 30,000−70,000), poly(D,L-lactide-co-glycolide) (PLGA, lactide glycolide 50:50, Mw = 700,0−17,000), tetraethyl orthosilicate (TEOS, >99%), ammonium hydroxide solution (NH4OH, 28−30%), 3aminopropyltriethoxysilane (APTES, H2N(CH2)3Si(OC2H5)3, 99%), fluorescein isothiocyanate isomer (FITC, >90%), and rhodamine B isothiocyanate (RBITC) were obtained from Sigma-Aldrich (USA). All chemicals were used as-received without further purification. B
DOI: 10.1021/acs.langmuir.7b04143 Langmuir XXXX, XXX, XXX−XXX
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Scheme 1. Schematic Diagrams Showing (a) Emulsion Solvent Evaporation Method Used To Synthesize IONP-Encapsulated PLGA Nanocomplexes (IPNs), (b) Synthesis of IPNs with Different Amounts of IONPs Loaded To Control Their Response to a Magnetic Field, (c) Experimental Process Used To Measure Magnetic Response Kinetics, and (d) Formation of Laminated Layers due to Differences in the Responsiveness of IPNs to a Magnetic Field
For measuring magnetic response kinetics of IPNs, a neodymium magnet was placed on top of a polystyrene cuvette containing IPN solution and absorbance kinetics of samples were measured at a wavelength of 500 nm with an interval of 10 s. To visualize the response of the samples to a magnetic field, they were labeled with fluorescent dyes (FITC and RBITC).28,29 Each fluorescent dye was treated with APTES to modify isothiocyanate functional groups with silane. In more detail, 19.5 mg of FITC was reacted with 11.5 μL of APTES in 50 mL of ethanol for 24 h (42 °C, in dark room), whereas 6.5 mg of RBITC was reacted with 50 μL of APTES in 12 mL of ethanol for 2 days (room temperature, in dark room). After modification, silane-modified FITC and silane-modified RBITC were conjugated with silica-coated IPNs. Briefly, 45 mL of ethanol, 2 mL of water, and 0.25 mL of acetic acid were mixed by stirring. Then, 2 μmol silane-modified dye was injected into the solution. After 5 min of stirring, 1 mL of silica-coated IPNs was added to the solution and the reaction was allowed to proceed for 2 h (room temperature, in dark room). Fluorescent dye-labeled IPNs were separated and washed by centrifugation (15 000g, 15 min, 20 °C) using ethanol as a solvent and were finally dispersed in 1 mL of water. To measure fluorescent intensity kinetics, a polystyrene cuvette was filled with 250 μL of fluorescent dye-labeled IPNs. Fluorescent intensity of FITC and RBITC was measured at excitation/emission wavelengths of 485/525 and 545/575 nm, respectively, with 10 s intervals. To fabricate laminated layers, fluorescent dye-labeled IPNs were redispersed in water. Again, samples were dispersed in 1 mL of 15% acrylamide solution, and the mixtures were transferred to a narrow conical column. Several columns were used to observe the formation of laminated layers in a given period of time. A neodymium magnet was placed on the bottom side of the columns. After incubation, columns were heated at 80 °C for 1 h, inducing the gelation of acrylamide for fixation. Laminated layers in fixed columns were observed under a fluorescent microscope.
polymer, PLGA, by an emulsion-solvent evaporation method. In the oil phase, IONPs and PLGA both dissolved in chloroform. The IONP/PLGA solution was transferred to an aqueous solution of PVA and emulsified to form an oil-in-water emulsion. Through an evaporation process, nanocomplexes of IONPs encapsulated in PLGA, which is simply termed IPN, were formed. Because the IONPs were dispersible in chloroform due to the presence of oleic acid as a surface stabilizer, they remained in the oil phase and became encapsulated in PLGA. The TEM image in Figure 1a shows the morphology of IPNs with an average size of 100 nm.
Figure 1. TEM images of (a) bare and (b) silica-coated IPNs. (scale bar = 100 nm).
Silica Coating of Nanocomplexes. To confer surface functionality to the IPNs, surfaces of IPNs were coated with a silica layer. An optimized general Stöber method was used for coating. Because the silica surface is not only easy to be modified with various functional groups but also stable in biological condition, it has been generally used for conjugation of biomolecules such as DNA and protein in many biological applications.30−32 In the Stöber method, ammonia is usually used to promote silica hydrolysis and condensation, which results in the formation of silica particles or layers. The pH required for this is approximately 12. This high pH, however, induces the hydrolysis of PLGA, resulting in the degradation of nanocomplexes, as shown in Figure S2. To overcome this problem, the silica layer should form before the degradation of
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RESULTS AND DISCUSSION Formation of Nanocomplexes Composed of PLGA and IONPs. IONPs were synthesized by thermal decomposition as reported previously.26 The size and shape of IONPs were visualized by transmission electron microscopy; TEM images (Figure S1 in the Supporting Information) revealed spherical IONPs with a uniform diameter of 6 nm. As demonstrated in Scheme 1a, IONPs were encapsulated in a C
DOI: 10.1021/acs.langmuir.7b04143 Langmuir XXXX, XXX, XXX−XXX
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Figure 2. TEM images of silica-coated IPNs synthesized with different amounts of IONPs. (a) 50, (b) 100, (c) 200, and (d) 400 mg/mL of IONPs were used (scale bar = 200 nm). (e) EE and the LE of IONPs per unit IPNs were plotted against the concentration of IONPs.
Figure 3. (a) Magnetization of silica-coated IPNs synthesized with different amounts of IONPs and (b) relation between saturation magnetization and concentration of IONPs used in the synthesis. (c) Magnetic response kinetics of bare (solid lines) and silica-coated (dashed lines) IPNs synthesized with different amounts of IONPs. After 5 min, a magnetic field was applied to the top side of the cuvette and the optical density change of the IPN solution was measured at a wavelength of 500 nm for 1 h and normalized by the initial sample value to determine the amount of IPNs remaining at set times.
chloroform was varied, resulting in different concentrations of IONPs in solution. The concentration of IONPs ranged from 50 to 400 mg/mL. TEM images in Figure 2 and SEM images in Figure S3 show that the silica-coated IPNs had a similar morphology regardless of IONP concentration; they were spherical with a diameter of 100 nm, and 50 nm thick silica layer covering the IPNs was observed by TEM. In addition, when we measured the size of the IPNs by using DLS, each IPN has a constant mean size of ∼100 nm and narrow size distribution, regardless of how many IONPs it contains (Figure S4). When an emulsion solvent evaporation method is employed to synthesize nanoparticles, the size of the obtained nanoparticles can be influenced by several factors including amount of polymer, volume of oil phase, and volume of aqueous phase. We speculated that the concentration of PLGA
PLGA. To address this problem, the amount of TEOS used as a silica precursor was increased, which accelerated the reaction rate of TEOS hydrolysis. Silica-coated IPNs were visualized by TEM; when more than 500 μL of TEOS was used, a silica layer was formed without any deterioration of nanocomplexes (Figure 1b). The thickness of the silica layer was approximately 50 nm. Formation of Nanocomplexes with Controllable Amount of Loading Nanoparticles. We hypothesized that the response of silica-coated IPNs to a magnetic field can be controlled by the amount of IONPs loaded into the nanocomplexes. To test this hypothesis, we synthesized IPNs with different amounts of IONPs. As shown in Scheme 1b, the amount of IONPs was fixed, whereas the volume of PLGA solution (concentration of PLGA was fixed at 10 mg/mL) in D
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Figure 4. (a) Fluorescent intensity kinetics of dye-labeled IPNs under an applied magnetic field. FITC and RBITC were conjugated with IPNs synthesized using 50 and 400 mg/mL IONPs, respectively. (b) Fluorescent microscopy images showing laminated layers of the two different dyelabeled IPNs. Red and green fluorescence correspond to RBITC and FITC, respectively.
IONPs was observed. Magnetization is defined as the density of magnetic moment in a material. In particular, the magnetic moment of IONPs can be determined during fabrication by changing various factors, such as media composition, FeII/FeIII ratio, temperature, injection flux, iron concentration, and fabrication method.34−36 Because the obtained magnetic moment is an extensive property that depends on the amount of materials, magnetization is calculated by dividing magnetic moment by total mass or volume of the measured sample. In this case, the magnetization value is represented with the specific units, emu/g or emu/cm3. Because the magnetization units are based on the unit of mass or volume of magnetic materials, as long as the inherent superparamagnetic property of IONPs is unchanged, there would be no difference in magnetization. However, in our study, the mass ratio of IONPs in the total nanocomplex was dependent on the concentration of IONPs used in the emulsification step. As a result, the magnetization of IPNs was dependent on the concentration of IONPs used in the emulsification step, even though we used the same amounts of IONPs for the fabrication of IPNs. Next, we investigated the response of the IPNs to an external magnetic field. UV−vis spectroscopy and a neodymium magnet were employed to determine the change in the optical density of bare IPNs and silica-coated IPNs under an applied magnetic field (Scheme 1c). As the absorbance of silica-coated IPNs was high in the UV region (Figure S7) and gradually decreased in the green light region, measurements were conducted at a wavelength of 500 nm. A plot of optical density at 500 nm versus time showed that the response of IPNs to a magnetic field varied according to the concentration of IONPs used in the synthesis (Figure 3c). IPNs synthesized using higher concentrations of IONPs showed a faster change in optical density, indicating a stronger response to the magnetic field. It should be noted that bare and silica-coated IPNs had similar kinetics, indicating that the effect of the silica coating on the IPN response to a magnetic field was negligible. Visualization of the Responses of Nanocomplexes to a Magnetic Field. The results described above confirmed that silica-coated IPNs with different responses to a magnetic field could be synthesized by varying the concentration of IONPs. Next, we demonstrated that the difference in response to the magnetic field could be visualized. Silica-coated IPNs
was the dominant factor influencing the variation in size of the nanoparticles. As PLGA functioned as a substrate for IONPs, fixing the concentration of PLGA resulted in the formation of IPNs with the same volume. This has also been reported in a previous study.33 IPN morphology changed notably at much lower or higher concentrations of IONPs (Figure S5). To validate each IPN of unique concentration of IONPs, EE and LE of IONPs in unit IPNs were calculated. Before the calculation, to determine the quantitative relationship between absorbance and concentration of IONPs, a standard curve was plotted by measuring the absorbance of various concentrations of IONPs in chloroform (Figure S6). The amounts of encapsulated IONPs were calculated by measuring absorbance of IPNs dissolved in chloroform solution and comparing it with the standard curve. Amounts of encapsulated IONPs were 9.6, 16.0, 21.8, and 26.9 mg for IPNs with 50, 100, 200, and 400 mg/mL of IONPs, respectively. The calculation formula for the EE and the LE is EE =
weight of encapsulated IONPs weight of introduced IONPs
LE =
weight of encapsulated IONPs (weight of introduced PLGA) + (weight of encapsulated IONPs)
The EE was calculated by dividing the amount of encapsulated IONPs by the amount of introduced IONPs. The LE of IONPs in unit IPNs was calculated by dividing the amount of encapsulated IONPs by total weight of PLGA and encapsulated IONPs. Calculated values were plotted against the concentration of IONPs with which each IPN was prepared (Figure 2e). The EE and the LE of IONPs were varied from 9.6 to 26.9 and 32.4 to 91.5%, respectively. Control of the Magnetic Strength of Nanocomplexes by Varying the Amounts of Nanoparticles Loaded. Magnetization of silica-coated IPNs synthesized using different concentrations of IONPs was determined. Samples were frozen, and their magnetization was measured using VSM. Obtained M−H curves of the samples had a typical superparamagnetic shape (Figure 3a). Saturated magnetization ranged from ∼1.7 to ∼7.6 emu/g based on the IONP concentration. As shown in Figure 3b, a linear relationship (R2 = 0.96) between saturated magnetization and concentration of E
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synthesized using 50 and 400 mg/mL IONPs were labeled with fluorescent dyes (FITC or RBITC). To verify that silicacoated IPNs could be labeled with fluorescent dyes, a microscale silica gel was labeled with these dyes using the same conjugation method. Both fluorescent dyes were successfully conjugated with the silica gel based on fluorescent microscope observations (Figure S8). The fluorescent intensity kinetics of two different dye-labeled IPNs in a cuvette were measured using a similar method as was used to measure the response of IPNs to a magnetic field. As shown in Figure 4a, different fluorescent kinetics were observed for the two types of dye-labeled IPNs. To visualize the difference in response to a magnetic field, the two different types of dye-labeled IPNs were transferred to an acrylamide solution, which was then transferred into a narrow conical column. As shown in Scheme 1d, when a neodymium magnet was placed on the bottom side of the column, the labeled IPNs responded to the external magnet by moving to the side. Upon heating, the labeled IPNs were captured and observed by fluorescent microscopy. Red and green fluorescence signals were mixed in the absence of an external magnetic field (0 h) (Figure 4b). After 30 min, red fluorescence was seen on the bottom side of the column, whereas green fluorescence was observed on the upper side, indicating the formation of red-green laminated layers. These laminated layers were considered to form as a result of the difference in response of the two different types of dye-labeled IPNs to a magnetic field. The RBITC-labeled IPNs responded to a magnetic field faster than the FITC-labeled IPNs because of the larger amount of IONPs present in the former. They therefore occupied the bottom layers. It should be noted that after 4 h, green fluorescent particles reached the bottom and mixed with the red fluorescent particles.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.7b04143.
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TEM image showing 6 nm IONPs, TEM images of silica-coated IONP-encapsulated PLGA nanocomplexes (IPNs) synthesized using 25 μL TEOS for different reaction times, SEM images of silica-coated IPNs synthesized with different amounts of IONPs, TEM images of bare and silica-coated IPNs, UV−vis spectra of silica-coated IPNs synthesized with different amounts of IONPs, and fluorescent microscopy images of RBITCand FITC-doped silica microparticles (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Seung Won Shin: 0000-0002-3437-4161 Sang Jun Sim: 0000-0003-1045-0286 Dan Luo: 0000-0003-2628-8391 Soong Ho Um: 0000-0002-2910-5629 Author Contributions
S.S.H.C. and S.W.S. contributed equally to this work. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Funding
This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI16C1984) and by grants from Basic Science Research Programs through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (grant nos. 2016R1D1A1B03931270 and 2017R1D1A1B03027897).
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CONCLUSIONS In this study, IONP-encapsulated PLGA nanocomplexes (IPNs) were fabricated by the simple method of emulsion solvent evaporation. Prepared IPNs showed a superparamagnetic property, and their magnetic behavior could be controlled in a quantitative manner without significant size variation of IPNs. For the application of superparamagnetic nanomaterials, particularly in biomedical fields, including contrast agent for MRI, heat generator for hyperthermia treatment, and carrier for drug or gene delivery, nanomaterials should be prepared in the proper range of size to avoid various obstacles in vivo. On the other hand, the weak magnetic moment of single-core IONPs should be overcome for effective utilization. The IPNs shown in this work contained many IONPs at a fixed size to enhance the magnetic behavior with adoptable size for biomedical applications. Furthermore, silica encapsulation of a nanocomplex provides the possibility of versatile surface modification. Various motifs can be conjugated on the silica surface for proper surface charge, functional group, or other specific purposes. In a view of their proper size, controllable magnetization, and easy surface modification, we expect the IPNs introduced in this work to have potential for use in various biomedical applications we mentioned above. Among them, our on-going project will cover the gene expression system based on the nanocomplexes. In the upcoming study, advantages and superiority of the nanocomplexe-based system will be discussed in the practical point of view.
Notes
The authors declare no competing financial interest.
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DOI: 10.1021/acs.langmuir.7b04143 Langmuir XXXX, XXX, XXX−XXX
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DOI: 10.1021/acs.langmuir.7b04143 Langmuir XXXX, XXX, XXX−XXX
