In situ functionalization of gadolinium oxide nanoparticles with polyethylene glycol (PEG) by pulsed laser ablation in a liquid medium (PLAL)

We characterized their shape and morphology using transmission electron microscopy (TEM), and confirmed their crystalline structure with X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) in combination with energy-dispersive X-ray spectroscopy (EDX) elemental mapping.

Journal of Science: Advanced Materials and Devices (2018) 419e427 Contents lists available at ScienceDirect Journal of Science: Advanced Materials and Devices journal homepage: www.elsevier.com/locate/jsamd Original Article In situ functionalization of gadolinium oxide nanoparticles with polyethylene glycol (PEG) by pulsed laser ablation in a liquid medium (PLAL) Atika Dougherty a, b, c, *, Clint Harper c, Ferry Iskandar a, d, Idam Arif a, Geoff Dougherty c a Department of Physics, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Indonesia, Jl Ganesha 10, Bandung 40132, Indonesia Department of Physics, Faculty of Science and Technology, Nusa Cendana University, Jl Adi Sucipto, Kupang 85001, Indonesia Applied Physics and Medical Imaging, California State University Channel Islands (CSUCI), Camarillo, CA 93012, USA d Research Center for Nanosciences and Nanotechnology, Institut Teknologi Bandung, Bandung 40132, Indonesia b c a r t i c l e i n f o a b s t r a c t Article history: Received 18 July 2018 Received in revised form 22 August 2018 Accepted 24 August 2018 Available online 30 August 2018 Gadolinium oxide (Gd2O3) nanoparticles with paramagnetic properties and biocompatible surfaces are promising materials for bioimaging applications We synthesized in situ pegylated Gd2O3 (Gd2O3@PEG) nanoparticles by liquid phase pulsed laser ablation (PLAL) of a gadolinium target in a polyethylene glycol (PEG) liquid medium We characterized their shape and morphology using transmission electron microscopy (TEM), and confirmed their crystalline structure with X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) in combination with energy-dispersive X-ray spectroscopy (EDX) elemental mapping The magnetic properties of the nanoparticles were characterized by vibrating sample magnetometry (VSM) We have found that the crystalline nanoparticles generated have a spherical shape and a narrow distribution with average diameters of 15.0, 11.6, and 6.0 nm, for PEG concentrations of 0.01, 0.05, and 0.10 mM, respectively We verified that partially oxidized molecules of PEG are attached to the nanoparticle surface as carboxyl groups An analysis of the magnetization of Gd2O3@PEG nanoparticles revealed highly paramagnetic properties Consequently, PLAL forms a green synthesis of Gd2O3@PEG, opening up new opportunities for bioimaging applications © 2018 The Authors Publishing services by Elsevier B.V on behalf of Vietnam National University, Hanoi This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Keywords: Synthesis Functionalization Gadolinium oxide Nanoparticles Pulsed laser ablation Biocompatible Introduction Gadolinium is a remarkable paramagnetic material due to the transition metal Gd3ỵ ion having seven unpaired electrons with a spin quantum number, s ¼ 7/2, which is the largest value among the elements in the periodical table [1] The spin number of the Gd3ỵ ion results in the highest longitudinal relaxation, making gadolinium-based materials popular in MRI imaging as T1 MRI contrast agent; gadolinium-based contrast agents are used in 45% of all MRI diagnosis imaging [2] The Gd3ỵ ion has the highest Xray absorption coefcient, which is very useful for CT scan * Corresponding author Applied Physics and Medical Imaging, California State University Channel Islands (CSUCI), Camarillo, CA 93012, USA Fax: ỵ1 8054378864 E-mail addresses: atika.ahab@mail.com (A Dougherty), clint.harper@usa.com (C Harper), ferry.iskander@email.com (F Iskandar), idam.arif@asia.com (I Arif), geoff.dougherty@csuci.edu (G Dougherty) Peer review under responsibility of Vietnam National University, Hanoi applications, and the gadolinium isotope 157Gd has the highest thermal neutron cross section contributing to its use for thermal neutron capture therapy (CNT) [3] Consequently, gadolinium materials have the possibility of being developed as multifunctional contrast agents According to the Salomon-Bloemberger-Morgan (SMB) theory, the performance of a MRI contrast agent can be improved by modifying the ligand design to provide a large hydration number and longer rotation time [4] During the last decade, there have been studies to improve the sensitivity of MRI contrast agents by chelating magnetic ions to form a chelate complex An alternative strategy is to accumulate a high number of magnetic metal atoms in a nanoparticle form Studies on the fabrication of inorganic gadolinium nanoparticles have shown that they can be easily functionalized with other materials, have the ability to carry large ion magnetic materials in their center, and have reduced molecular tumbling rates, which lead to enhanced relaxation time [5] https://doi.org/10.1016/j.jsamd.2018.08.003 2468-2179/© 2018 The Authors Publishing services by Elsevier B.V on behalf of Vietnam National University, Hanoi This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) 420 A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 Among all inorganic gadolinium based nanoparticles, gadolinium oxide (Gd2O3) nanoparticles are very attractive for such applications due to their high paramagnetism, which depends on their size, and low toxicity [6] Based on these properties, pegylated Gd2O3 (Gd2O3@PEG) nanoparticles have been synthesized using modified thermal decomposition and solvothermal-calcination methods, which provided in situ synthesis of functionalized Gd2O3 nanoparticles [7] However, using these methods the nanoparticle products had large nano diameter sizes which we believe was due to the slow heating processes and non-uniform temperature distributions To solve the issue, our group has developed a physical approach to the chemical method, whereby the thermal decomposition can be performed using pulsed laser ablation in a liquid environment (PLAL) to produce pegylated Gd2O3 (Gd2O3@PEG) nanoparticles PLAL is a top-down technique for nanocolloid fabrication, which uses a focused short or ultrashort pulsed laser to ablate a solid target, submerged beneath a liquid [8, 9] PLAL was introduced by Patil et al [8], where a metastable phase of iron oxide was synthesized by ablating an iron target It was demonstrated to be an effective, simple, and versatile method for synthesizing nanoparticles The resulting nanoparticles are non-toxic and stable when they are produced in biocompatible solutions [10,11] Another advantage is their independence from chemical precursors, avoiding the use of toxic substances or by-products that could possibly impose toxicity or block the surface against further functionalization [12] Since the resulting nanoparticles are in pure colloidal solution, there is the opportunity for further nanoscale manipulations such as biofunctionalization [13,14], for biological sensing, imaging, and therapeutics The parameters of the PLAL need to be carefully considered in order to produce monodisperse nanoparticles The critical parameters are the near-infrared (NIR) wavelength, the pulse duration in nanoseconds, and the irradiance at its mid value [15,16] In addition, the liquid environment also affects the generated nanoparticles, and the polyol liquid medium serves as a template, surfactant, and biocompatible nanoparticle layer [11] The use of polyol as a liquid medium is a template that drives the shape of the nanoparticles to become spherical [17,18] For the present study, we carried out PLAL of gadolinium foil in PEG It should be noted that a synthesis of Gd2O3@PEG nanoparticles using PLAL in a PEG liquid medium has not previously been reported To our knowledge, to date there have been only several studies of gadolinium nanoparticles prepared by PLAL Synthesis of gadolinium oxide nanoparticles using PLAL was successfully carried out by using a gadolinium plate ablated with nanosecond pulses from an Nd: YAG laser and ethanol, water, and acetone as the liquid medium [19] The gadolinium nanoparticles had a spherical shape and were monodisperse, and stable against temperature and high pressure Cueto et al [11] successfully synthesized platinum nanoparticles using laser ablation of a platinum target in PEG solvent They observed that the nanoparticles had a spherical shape with a smaller diameter and a sharper size distribution compared to the nanoparticles produced by laser ablation in water In addition, Besner et al [10] found that gold nanoparticles produced by PLAL using a PEG solution as medium were covered with PEG groups which are useful in biomedical applications In this paper, we report on a facile synthesis of a colloidal solution of Gd2 O3@PEG nanoparticles by ablating a gadolinium target in PEG solvent The effects of PEG on the properties of the Gd2 O3 nanoparticles such as morphology, particle size, crystallization, and magnetic properties have been investigated We also investigated the functionalization mechanism of PEG molecules on gadolinium Experimental 2.1 Synthesis of Gd2O3@PEG nanoparticles using PLAL A 99.99% pure gadolinium foil (SigmaeAldrich, Singapore) of size   mm3 was first polished with sandpaper, cleaned in an ultrasonic bath for 30 and dried in an air dry oven The Gd target was immersed in liquid PEG and then ablated by a nanosecond Nd: YAG laser (l ¼ 1064 nm) The laser had an energy of 19.80 mJ/pulse, repetition rate 10 Hz, and pulse duration ns The laser spot at the target surface was kept constant at a diameter of 350 mm using a lens with a focal distance of 16.50 cm The target was placed in a stage control, and the depth of the liquid above the target was cm Under these conditions the resulting fluence was 21.53 J/cm2 The experiment was conducted using PEG of different concentrations (1 kDa, Merck, 0.01, 0.05, 0.1 mM) to investigate the effects of the concentration of the PEG stabilization agent on the nanoparticle products For each PEG concentration, the ablation procedure was completed in Immediately after ablation, the optical absorption spectra of the resulting colloids were measured by a UV visible spectrophotometer (Fig 1) The PLAL products synthesized in 0.01, 0.05, and 0.10 mM PEG are assigned to as GdOa, GdO-b, and GdO-c, respectively 2.2 Sample preparation for analysis A transmission electron microscope (TEM) and high resolution TEM (HRTEM) (JEOL-2100F 200 kV) were used to determine morphology, size distribution, and Selected Area Electron Diffraction (SAED) of nanoparticles For this characterization, the nanoparticle suspensions were dispersed by sonification, spotted onto a carbon-coated Cu grid, and then air-dried at room temperature The electron dispersive X-ray analysis system (EDX 20 kV, Oxford EDS system) attached to a scanning electron microscope (Tescan GAIA 3) was used to collect chemical information on the resulting nanoparticles Powder phase composition, its crystalline structure, lattice parameters, and grain size were determined using X-ray diffraction spectroscopy (XRD, Rigaku Smartlab, Cu-Ka at 40 kV 44 mA) X-ray photoelectron spectroscopy (XPS) spectra were acquired on a Kratos Axis Ultra spectrometer with a monochromatic Al Ka X-ray source (1486.6 eV) using a pass energy of 20 eV The photoelectron take-off angle was 90 with respect to the sample plane To provide a precise energy calibration, the XPS binding energies were referenced to the C1s peak at 284.6 eV Fig Optical absorption spectra of Gd colloid solution produced by laser ablation of gadolinium foil in 0.01 mM PEG The inset shows an Absorption Spectrum Fitting (ASF) plot to determine the band gap energy of the prepared sample A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 Sample preparation was carried out by transferring a drop of colloidal solution on to a single crystal silicon substrate for SEM, EDX, and XPS characterizations and on to a glass substrate for XRD analysis followed by drying at room temperature The magnetic properties of the samples were characterized using a vibrating sample magnetometer (VSM, DynaCool PPMS) A sample for VSM measurement was prepared by drying the precipitation products of PLAL at 60  C for 12 h Results and discussion 3.1 Band gap, morphology and size Fig shows an illustrative UV-visible spectrum of a Gd colloid sample prepared by ablating gadolinium foil in 0.01 mM PEG-1000 The Gd colloids formed under laser ablation exhibit featureless optical absorption spectra A small peak at 267 nm in the spectra may indicate the presence of Gd elements [20] Since the sample was expected to have semiconductor properties, the band gap energy (Egap) of the sample was determined using absorption spectrum fitting (ASF) (inset, Fig 1) derived from the Tauc model [21] By using the linear region at D ¼ 0, extrapolation of the (D/l)2 versus lÀ1 curve results in a value for Egap of 5.2 eV (for 0.01 mM PEG) The band gap was found to be 5.24 eV and 5.38 eV for 0.05 mM and 0.10 mM PEG-1000 respectively These results are close to the reported value of the direct band gap for materials made from the oxide nanocolloid of Gd2O3 [22] The PLAL products have a higher value of Egap compared to theoretical results for monoclinic phase Gd2O3 (Egap ¼ 3.8 eV) This may be due to the microstructure of the particles and the presence of functionalization ligand groups in the colloid samples [23] In general, the band gap reflects the degree of crystallinity and particle size [24,25] The increasing values of Egap with increasing PEG concentrations during synthesis may reflect decreasing sizes of the resulting nanoparticles The morphology and size of the nanoparticles were characterized by TEM The micrographs depicted in Fig show the spherical morphology of the particles synthesized by the laser ablation The characteristic shape obtained is most probably due to the PLAL process and the phenomena that lead to the spherical shape of nanoparticles, in the same manner as for nanoparticles obtained using water medium [26] The spherical shape growth phenomena of Gd-based nanoparticles produced by using PLAL can be described as follows; (i) when the gadolinium target is ablated by nanosecond laser pulses, gadolinium atoms and ions are ejected from the gadolinium target into PEG the moment the laser energy is absorbed by the Gd target (ii) The ejected gadolinium active species react with oxygen from the liquid and form an initial oxidized Gd cluster These clusters in close vicinity aggregate rapidly to form Gd-based nanoparticles and simultaneously form a region void of Gd clusters since the clusters are consumed almost completely resulting in embryonic Gd-based nanoparticle [27,28] However, the supply of gadolinium atoms outside the void region causes the particle to grow slowly through diffusion (iii) By using the PEG as a liquid medium, PEG terminates the diffusion of Gd clusters in competition with the slow growth of nanoparticles As a result, the interatomic interaction between the active surface of Gd nanoparticles and partially oxidized products of PEG molecules dominates, resulting in PEG-coated Gd nanoparticles Since the Gd nanoparticles are now coated with PEG, further growth of the nanoparticles is prohibited in any direction, and the shape of the nanoparticles becomes spherical To examine the use of PEG as a reducing agent, the concentration of PEG was gradually increased as the liquid medium in the synthesis process Statistical analysis of TEM size (Fig 2) indicates that the Gd nanoparticles, synthesized at 0.01, 0.05, and 0.10 mM 421 PEG-1000 have a spherical shape with mean feret diameters of 15.0, 11.6, and 6.0 nm and standard deviation of 0.44, 0.69, and 0.28 nm, respectively The majority of the particles were of average size, but a few particles of size >20 nm were also found in the samples From our TEM results for the sample synthesized at 0.10 mM, the mean size distribution of Gd nanoparticles is lower than the Gd2O3 produced by PLAL using only water Thus, PEG at concentrations !0.01 mM has an important influence on the size of the resulting Gd nanoparticles This can be explained through the LifshitzSloyzov-Wagner (LWS) theory which implies that the size of the final particles in a wet synthesis process is related to the viscosity through r f 1/h, where r is the radius of the particle product, and h is the viscosity of the solvent [29] This suggests that by increasing the PEG concentration, the viscosity of PEG increases and the size of the Gd nanoparticles decreases concomitantly Higher PEG concentrations are probably a factor in terminating the diffusion of Gd clusters immediately after ablation, resulting in smaller nanoparticles PLAL is a physical approximation of the thermal decomposition synthesis method Compared to that method, chemical heating of solvents/reaction mixtures is a slow heating process as it involves the thermal conductivity/barriers of various materials involved, such as the reaction vessel itself Moreover, the surface of the reaction vessel in contact with the heating source is always at a higher temperature than the rest of the reaction medium, leading to a non-uniform distribution of temperatures throughout the reaction mixture In the synthesis of nanomaterials, this can result in large particle size with a wide distribution as reported when synthesizing pegylated Gd2O3 nanoparticles using the thermal decomposition method [7] In that work, the synthesized Gd2O3@PEG nanoparticles had an average diameter of 178 nm In comparison, PLAL synthesis involves a direct transfer of high energy from the NIR laser to the reaction medium, causing rapid and homogenous heating of the reactants, which minimizes thermal gradients and provides uniform nucleation and growth conditions resulting in the formation of nanomaterials with a uniform size distribution [15,30] Moreover, such rapid energy transfer creates non-equilibrium conditions in the reaction mixture, resulting in high instantaneous temperatures locally, thus reducing the reaction time and improving the crystallinity of the product [30] In this work, by using PLAL the gadolinium target foil was ablated in PEG liquid medium to produce Gd-based nanocolloids It can be clearly seen in Fig 2, the nanoparticles resulting from PLAL are smaller than 100 nm and have a sharper size distribution, in contrast to the material synthesized by the thermal decomposition method 3.2 Crystallinity and phase In order to study how nanosecond laser radiation centered at 1064 nm determined the crystallinity and phase of the samples, the colloid samples were deposited on quartz substrates at ambient temperature and pressure and analyzed by X-ray diffraction spectrometer Fig displays the XRD patterns of three samples with three different concentrations of PEG The materials show similar peaks, an intense peak at 2q ¼ 29.47 and low intensity peak relative to the first one at 42.12 The first peak is associated with the crystalline plane ð402Þ, and the second with the plane ð313Þ of monoclinic Gd2O3 with C2/m group space (the Miller index and d inter-planar spacing for monoclinic Gd2O3 are included in JCPDS: 42e14650) The XRD patterns show broadening at the peaks that were attributed to carbon materials from the molecular coating of the particles, i.e polyethylene glycol [31], similar to what was observed €derlind et al in pegylated Gd2O3 nanocrystals, as reported by So 422 A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 Fig Morphology and size distribution of Gd-based nanoparticles synthesized by PLAL using (a) 0.01 mM, (b) 0.05 mM, and (c) 0.10 mM PEG [31], Faucher et al [32], and Ahab et al [7]) This indicates that after being ablated, PEG molecules attach to the ablation product These results are further confirmed by XPS From the samples GdO-a to GdO-c there is a loss of crystal order detailed by the shape of the peaks The peak shapes become progressively more broadened in intensity However, the number of peaks and the position of each peak stays the same showing that there is no new crystal system formed at higher PEG concentrations This increased broadening around the main peaks of the diffraction spectrum is due to hydrocarbon chains of the PEG being higher at higher PEG concentrations [33] Typical HRTEM images of Gd2O3@PEG ablated nanoparticles ablated at 0.01 mM are shown in Fig 4(a) Fig 4(b) shows the ring patterns of selected area electron diffraction (SAED) which are consistent with the ð201Þ, ð202Þ, ð202Þ, and ð402Þ planes of the monoclinic Gd2O3 structure This is well supported by our X-ray powder diffraction data results The regularity of the lattice plane in the HRTEM image (Fig 4(b)) clearly indicates that the Gd2O3@PEG nanoparticles are typical of polycrystalline material and show that the sample is well-crystallized Fig 4(c) shows lattice fringes from an individual crystal with the space between adjacent planes, d, equal to 0.31 nm corresponding to the (111) crystal plane of the monoclinic phase of Gd2O3 (JCPDS: 42-14650 individual crystal with the space between adjacent planes, d, equal to 0.31 nm corresponding to the (111) crystal plane of the monoclinic phase of Gd2O3 (JCPDS: 42-14650) A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 423 increase at the center of the nanoparticle The existence of the carbon element on the nanoparticle confirms that the PEG molecules successfully attached to the Gd2O3@PEG surface The elemental maps of Gd2O3@PEG nanoparticles are presented in Fig Gd, O, and C maps characterize the nanoparticle surface, revealing that our PLAL fabrication route produces functionalization of PEG to Gd2O3 nanoparticle surfaces with a homogeneous distribution It can be seen that the entire particle surface consists of Gd, O, and C 3.4 Functionalization Fig X-ray diffraction patterns of the samples produced by laser ablation of Gd target in solutions of (a) 0.01 mM, (b) 0.05 mM, and (c) 0.10 mM PEG 3.3 Elemental analysis The SEM micrograph displayed in Fig 5(a) shows the spherical morphology of the particles synthesized by the laser ablation method, and the EDX spectrum shown in Fig 5(b) reveals the presence of elements such as gadolinium (Gd), oxygen (O), and carbon (C) The SEM-EDS line scan and the scan region of a Gd2O3@PEG nanoparticle surface are shown in Fig 5(c) and (d), revealing that the chemical element contents of Gd, O, and C X-ray photoelectron spectroscopy (XPS) is a surfaceesensitive technique, probing the outermost 5e10 nm of the magnetic nanoparticles In this work, XPS spectra were studied to determine functionalization of the PEG molecules to the Gd2O3 nanoparticles and to analyze the Gd oxidation state so as to determine which chemical valence state is responsible for the magnetization properties The preparation of the samples for XPS was carried out by deposition of a droplet of the colloidal sample onto a silica wafer which was dried overnight at ambient temperature and pressure Fig shows the Gd3d, C1s, and O1s XP spectra of the PLAL samples prepared in 0.01, 0.05, and 0.10 mM of PEG1000 The Gd3d XPS spectra of all the samples have been deconvolved to show the two major components at 1219.85 and 1187.65 eV corresponding to a spineorbit splitting of 32.20 eV resulting in the 3d3/2 and 3d5/2 energy level for Gd [34] The spectra of samples prepared in 0.01 and 0.10 mM (Fig 7(a), (g)), at higher binding energy components merely broadens and featureless with significant satellite peak located near higher BE but at 0.05 mM, the peak is sharp and has Fig (a) HRTEM micrograph of monoclinic Gd2O3@PEG nanoparticles ablated at 0.01 mM PEG-1000, (b) selected area electron diffraction (SAED) pattern, (c) an individual Gd2O3@PEG nanoparticle, and (d) its fast Fourier transform 424 A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 Fig (a) SEM image of Gd2O3@PEG nanoparticles from the laser ablation of Gd foil in 0.01 mM PEG-1000 and (b) EDX spectrum of the nanoparticles (c) The arrow in Fig 5(a) indicates the EDX line scan position of a Gd2O3@PEG nanoparticle and (d) the EDX line scan using the Gd La, O Ka, and C Ka signals higher intensity compared to 0.01 and 0.10 mM samples These peaks may be due to the sample with 0.05 mM PEG containing more native Gd2O3 oxidized state (Table 1) In order to clarify the functionalization of PEG to the nanoparticle ablation products, a detailed analysis of the O1s and C1s spectra was undertaken The O1s spectrum of the samples shows four peaks The peak at 529.82 eV corresponds to the oxygen in the Gd2O3 in agreement with earlier XPS work on Gd2O3 [31] The peak at about 531.97 eV originates from the oxygen in the Gd À OH group in PEG [35], the peak at about 532.67 eV originates from oxygen in the ỒC ¼ O group [36], and the peak about 533.35 eV originates from oxygen in the GdeCO3 group [37] The deconvolution of the C1s XPS spectra (Fig 7(c), (f), (i)) reveals the existence of peaks which can be assigned to the following: CeC and CeH groups at 285.05 eV, CeOH and CeOeO at 286.53 eV, OeC ¼ O at 288.30 eV,47e49 and GdeCO3 at 289.54 eV [37,38] An extended analysis of the XPS atomic concentration of Gd2O3 nanoparticle surfaces prepared in different PEG concentrations is shown in Table For the sample prepared in 0.01 mM PEG, the O1s GdeO spectrum corresponds to the formal (Gd3ỵ) oxidation state, as mentioned earlier, and has an intensity of 2.71% Using 0.05 mM PEG, the oxidation state of Gd2O3 is higher due to the shift of the GdeO spectra whereas the O1s intensity of the OeC]O group gradually increases The increasing OeC]O intensity is due to the consumption of oxygen in partially oxidized molecules of PEG from the surface of the nanoparticle when the concentration of PEG was increased [38] This unexpected result can be explained by our TEM results which show that this PEG concentration produced a smaller nanoparticle which induces a higher concentration of the gadolinium oxidized state (7.40% GdeO) on the nanoparticle surface However, when 0.10 mM PEG was used as the liquid medium in the PLAL system, the nanoparticle surfaces absorb more oxygen from the PEG resulting in a reduction of the oxidation state of Gd2O3 (GdeO, 2.81%) Moreover, increasing the PEG concentration resulted in increased Gd carbonate as well as reduced Gd hydroxide on the chemical surface of the nanoparticle product The results of the XPS analysis show PEG molecules functionalized to Gd2O3 nanoparticles have been produced by PLAL in a single step reaction During the ablation process, the high temperature partially oxidized the PEG solvent resulting in carboxyl functional groups (eOH and COOe) which attached to the Gd2O3 nanoparticle surface During our PLAL process, the nanoparticle surface had increased contact with water (H2O), eOH, and eCOOgroups of partially oxidized PEG products resulting in Gd hydroxides and Gd carbonate in the surface chemistry of the native Gd2O3 nanoparticle product This leads us to conclude that reactive Gd2O3 nanoparticle products interacted with water and oxidized PEG molecules at the very top surface layers with Gd carbonate, Gd hydroxide, and Gd oxide being localized at deeper surface layers Fig EDX elemental mapping of Gd2O3@PEG nanoparticles from laser ablation of Gd foil in 0.01 mM PEG-1000 A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 425 Fig Gd3d (left panels; a, d, g), C1s (middle panels; b, e, h), and O1s (right panels; c, f, i) XPS spectra of the pegylated Gd2O3 samples Table XPS atomic concentration of pegylated Gd2O3 at different concentrations Sample XPS Atomic Concentration (%) Oxygen Gd2O3 ỵ 0.01 PEG Gd2O3 ỵ 0.05 PEG Gd2O3 þ 0.10 PEG Carbon GdeO GdeOH OeC]O GdeCO3 CeC, CeH CeOH, CeC OeC]O GdeCO3 2.71 6.68 2.81 68.83 55.07 39.58 0.99 9.73 34.52 27.46 28.52 34.52 44.13 41.03 20.00 36.71 37.58 67.78 14.58 12.20 8.42 4.56 9.19 3.81 The carboxyl functional group plays an important role in dispersing the nanoparticles and functionalizing them to other organic materials Based on this understanding, we propose a surface design of Gd2O3@PEG nanoparticles synthesized by the PLAL method (Fig 8) 3.5 Magnetic properties The magnetization vs magnetic field (M-H) curves of the Gd2O3@PEG nanoparticle products at 0.01 (a), 0.05 (b), and 0.10 mM (c) PEG-1000 were investigated by VSM at room temperature (300 K) in applied magnetic fields ranging from À50 kOe to 50 kOe (Fig 9) In all cases, as expected, the particles exhibit a paramagnetic behavior The slope of the MÀH curves correspond to a susceptibility, c, of 1.87  10À4, 1.05  10À4, and 1.24  10À4, respectively, which is greater than the susceptibility of Gd2O3@PEG nanoparticles (c ¼ 8.2  10-5) synthesized by the chemical thermal decomposition method [7] The larger magnetization of Gd2O3@PEG nanoparticles produced by PLAL is due to the smaller size of the nanoparticles produced by this method At nanometric sizes, the ratio of surface spins to the total number of spins increases resulting in magnetization enhancement [39] The smaller magnetization of the GdO-b and GdO-c samples compared with the GdO-a sample, shown in Fig 9, is due to a diamagnetic layer of PEG molecules forming at increasing PEG concentrations which enhances biocompatibility and functionalization but reduces magnetic properties [40] This smaller magnetization can also be explained by considering a critical size of magnetic nanoparticles (in the range of 1e10 nm) In this size range, a magnetic nanoparticle consists of a single domain When the nanoparticle is reduced in size, its magnetization 426 A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 Fig A surface design of Gd2O3@PEG nanoparticles synthesized by PLAL in a PEG liquid medium Conclusion Fig Magnetic characterization of Gd2O3@PEG nanoparticles produced by laser ablation of Gd target in solution of (a) 0.01 mM, (b) 0.05 mM, and (c) 0.10 mM PEG at 300 K decreases due to increasingly disordered spins within the layer thickness [41] Previous studies of magnetic nanoparticles showed that the surface functionalization of small magnetic nanoparticles can reduce the layer thickness of disordered spins, thus increasing the magnetization [42] We hypothesize that the enhanced magnetization of the GdO-c nanoparticles relative to GdO-b is due to an increased number of chelating bidendate bonds arising from strongly covalent interactions between the Gd atoms and O2À from the carboxyl group on the Gd2O3 nanoparticle surfaces, which help to reduce the disordered layer This hypothesis is also confirmed by our O1s XPS results in which the reduction of OeC]O intensity suggests that the number of partially oxidized molecules absorbed into the Gd2O3 nanoparticle surfaces increases with PEG concentration The Gd2O3 nanoparticles with an appropriate surface modification for biomedical purposes were synthesized by a “green” method based on thermal decomposition We suggest that the more biocompatibility in the process, the more desirable will be the product for biomedical applications In situ production of Gd2O3@PEG nanoparticles via laser ablation was accomplished using a pure gadolinium foil target We explored the factors controlling the growth of the Gd2O3 nanoparticles and their functionalization with PEG used as a liquid environment in the PLAL method Our results suggest that PEG affects the size, morphology, and crystallization of the Gd2O3 nanoparticles and that the organic molecules of PEG-1000 successfully attached to the nanoparticle surface as carboxyl groups The Gd2O3@PEG nanoparticles have paramagnetic properties at ambient temperature, and they would serve as a multifunctional biomaterial such as a carrier, for targeting, or as a contrast agent Conflicts of interest There are no conflicts to declare Acknowledgements The work was partially supported by the PKPI Sandwich-Like 2016 program from the Directorate General of Higher Education and Ministry of Research and Technology, Indonesia, an ITB Research and Innovation Grant 2016, and by Applied Physics, California State University Channel Islands The authors would to thank Dr Amanda Strom (Material Research Laboratory, University of California, Santa Barbara) for assisting us with the XRD, XPS, and VSM measurements and providing useful comments related to the interpretation A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 References [1] K.N Raymond, V.C Pierre, Next generation, high relaxivity gadolinium MRI agents, Bioconjugate Chem 16 (2005) 3e8 [2] L.M Mitsumori, P Bhargava, M Essig, M.H Maki, Magnetic resonance imaging using gadolinium-based contrast agents, Top Magn Reson Imag 23 (2014) 51e69 [3] N Sakai, L Zhu, A Kurokawa, H Takeuchi, S Yano, T 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Synthesis of gadolinium oxide nanoparticles using PLAL was successfully carried out by using a gadolinium plate ablated with nanosecond pulses from an Nd: YAG laser and ethanol, water, and acetone as... nanoparticles using laser ablation of a platinum target in PEG solvent They observed that the nanoparticles had a spherical shape with a smaller diameter and a sharper size distribution compared... A Dougherty et al / Journal of Science: Advanced Materials and Devices (2018) 419e427 Among all inorganic gadolinium based nanoparticles, gadolinium oxide (Gd2O3) nanoparticles are very attractive