Multi-functional GdEu_xTb_1−xO₃ (x = 0 to 1) nanoparticles: colour tuning optical properties, water proton spin relaxivities, and X-ray attenuation properties

Abstract

Multi-functional nanoparticles are useful for various applications, such as biomedical imaging, detection, and display technologies. Colour-tunable GdEu_xTb_1−xO₃ nanoparticles were synthesized with emission colour ranging from green (545 nm) to red (616 nm) by varying x (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1). These nanoparticles were surface-grafted with polyacrylic acid and a small quantity of 2,6-pyridinedicarboxylic acid. This modification aimed to ensure long-term colloidal stability (>1 year without precipitation) and high quantum yields (>30%) in aqueous media. Additionally, they exhibited long emission lifetimes (∼1 ms), high longitudinal water proton spin relaxivities (>30 s⁻¹mM⁻¹), and high X-ray attenuation efficiencies (∼10 HU mM⁻¹). These multiple exceptional properties within a single nanoparticle make them highly valuable for applications in biomedical imaging, noise-free signal detection, and colour display.

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Introduction

The mixed lanthanide oxide (GdEu_xTb_1−xO₃) nanoparticles exhibit various optical and magnetic properties essential for applications in biology, medicine, and information technology, including biolabeling, diagnosis, and electronic displays.^1–5 These properties stem from the intrinsic electronic properties of 4f-electrons of the lanthanide elements,⁶ and their high atomic numbers, which enhance their X-ray attenuation power.⁷

In this study, gadolinium (Gd), europium (Eu), and terbium (Tb) were mixed to obtain GdEu_xTb_1−xO₃ nanoparticles, with Gd maintained at a nearly constant level to adjust the emission colour between green (545 nm from Tb) and red (616 nm from Eu)^1,2,8 by varying x (x = 0–1). Gd³⁺ is optically transparent in the visible region and has no effect on the colour.⁹ However, it significantly boosts longitudinal water proton spin relaxivities (r₁) due to its exceptionally high 4f-electron spin (s = 7/2) magnetic moment (μ = 7.9–8.0 emu g⁻¹), valuable for use as T₁ magnetic resonance imaging (MRI) contrast agents.^4,5,10–12

Lanthanides, as optical probes, exhibit exceptional properties such as long-term photostability, a large Stokes shift (the energy difference between excitation and emission wavelengths), sharp atomic-like transitions, long emission lifetimes, and resistance to photobleaching.^1,5,13,14 Consequently, they enable near background-free signal measurements with high detection limits,¹⁵ surpassing organic dyes and quantum dots (QDs). However, their drawback is low emission intensity due to forbidden 4f–4f electronic transitions,^1,16,17 making them less favoured as optical probes than organic dyes and QDs. Nevertheless, this can be significantly improved through photosensitization,^8,18–25 which is an electronic energy transfer process from organic chromophores to lanthanides. The photosensitized lanthanide materials in aqueous media emit strongly with high quantum yields (QYs),^8,22,23 comparable to or even surpassing those²⁶ of organic dyes.

Photosensitized GdEu_xTb_1−xO₃ nanoparticles were created in this study, embodying multiple-functionalities within a single nanoparticle. Until now, achieving colour tuning using Eu and Tb required varying doping ratios of Eu³⁺/Tb³⁺ ions in various nano to micro solid-state matrices^27–32 or mixing Eu³⁺/Tb³⁺ complexes in different ratios.^33–36 In this study, colour-tunable GdEu_xTb_1−xO₃ nanoparticles with multiple properties within a single nanoparticle, useful for various applications in solid-states and colloidal forms in aqueous media, were synthesized for the first time. After being grafted with hydrophilic and biocompatible polyacrylic acid (PAA) and a small amount of the organic photosensitizer 2,6-pyridinedicarboxylic acid (PDA), the GdEu_xTb_1−xO₃@PAA/PDA nanoparticle colloids maintained stability in aqueous media without precipitation after synthesis for >1 year, while emitting photons with high QYs. Photoluminescent (PL) spectra, colour tuning, absolute QYs, emission lifetimes, water proton spin relaxivities, and X-ray attenuation power of the nanoparticles were measured to unveil their multi-functional properties. Their key properties include colour tunability by varying x with high QYs, suitable for colour display applications; long emission lifetimes, beneficial for noise-free signal detection; and multiple imaging properties, useful for optical imaging, T₁ MRI, and X-ray computed tomography (CT).

Experimental

Materials

Gadolinium(III) chloride hexahydrate (GdCl₃·6H₂O, ≥99%), europium(III) chloride hexahydrate (EuCl₃·6H₂O, ≥99.9%), terbium(III) chloride hexahydrate (TbCl₃·6H₂O, ≥99.9%), PAA (M_w = ∼1800 amu), PDA (C₇H₅NO₄, ≥98.0%), dimethyl sulfoxide (C₂H₆OS, DMSO, ≥99.9%), tetramethylammonium hydroxide solution (C₄H₁₃NO, TMAH, 25 wt% in methanol), and dialysis tubes [molecular weight cut-off (MWCO) = 500 and 2000 amu] were purchased from Sigma-Aldrich (USA). Ethanol (C₂H₅OH, ≥99.0%) and sodium hydroxide (NaOH, >99%) were purchased from Duksan (South Korea). All chemicals were used as received. The synthesized nanoparticles were washed and dispersed using triple-distilled water.

Synthesis of GdEu_xTb_1−-xO₃@PAA nanoparticles

Fig. 1a schematically shows that 1 mmol GdCl₃·6H₂O, x mmol EuCl₃·6H₂O, and (1 − x) mmol TbCl₃·6H₂O (x = 0.1, 0.3, 0.5, 0.7, and 0.9) were dissolved in 15 mL DMSO with magnetic stirring in a three-necked round-bottom flask at 35 °C under atmospheric conditions. For x = 0 and 1, 1 mmol GdCl₃·6H₂O and 0.3 mmol LnCl₃·6H₂O (Ln = Eu or Tb) were used. After all precursors were dissolved, the solution became transparent. Subsequently, TMAH solution was added to maintain the solution pH at ∼8, followed by 24 h of magnetic stirring to yield mixed lanthanide oxide nanoparticles. In a separate beaker, 1 mmol of PAA was dissolved in 10 mL of DMSO under magnetic stirring to prepare the PAA solution. This solution was subsequently added to the nanoparticle solution, and TMAH solution was added to maintain the solution pH at ∼8. After 24 h of magnetic stirring, PAA-grafted nanoparticles were obtained. Ethanol (200 mL) was added to the solution, followed by centrifugation at 4000 rpm to purify PAA-grafted nanoparticles. This step removed top solutions containing DMSO, unreacted lanthanide precursors, TMAH, and PAA. After three repetitions of the washing process, the nanoparticles were dispersed in triple-distilled water. Subsequently, a 1 M NaOH solution prepared in triple-distilled water was added to adjust the solution pH to ∼8. The nanoparticles underwent further purification through 1 day of dialysis (MWCO = 2000 amu).

Fig. 1 Syntheses of (a) GdEu_xTb_1−xO₃@PAA nanoparticles and (b) GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1).

PDA grafting to obtain GdEu_xTb_1−-xO₃@PAA/PDA nanoparticles

The PDA grafting is schematically shown in Fig. 1b. PDA solutions at concentrations of 10, 20, 30, 40, and 50 μM were prepared in triple-distilled water. These solutions were then added to 4 mL of the prepared GdEu_xTb_1−xO₃@PAA nanoparticle solutions ([Eu] + [Tb] = 2 mM), and the mixtures were gently shaken for 1 min to yield GdEu_xTb_1−xO₃@PAA/PDA nanoparticles. The solutions underwent 1 day of dialysis (MWCO = 500 amu) to remove excess PDA. The optimal PDA concentration was determined by analyzing PL spectra to achieve the highest PL intensity.

Characterizations

The synthesized nanoparticles underwent various analyses, as previously detailed.⁸ These characterizations included particle diameter measurements using high-resolution transmission electron microscopy (HRTEM), metal composition determination using energy-dispersive X-ray spectroscopy (EDS), crystal structure analysis using X-ray diffraction (XRD), zeta potential measurements using a zeta size analyzer, metal composition determination and metal concentration analysis in aqueous media using inductively coupled plasma-atomic emission spectroscopy (ICP-AES), surface-grafting assessment of PAA and PDA on nanoparticle surfaces using Fourier-transform infrared (FT-IR) absorption spectroscopy, surface-grafting quantity determination of PAA and PDA using thermogravimetric analysis (TGA), Ultraviolet (UV)-visible absorption, PL, and excitation spectra, and fluorescence lifetimes measured with a PL spectrometer, absolute QYs assessed using an integration sphere in a PL spectrometer, phantom images and X-ray attenuation power measured using a CT scanner, water proton spin relaxivities and map images acquired using a 3 T MRI scanner at 22 °C, and evaluation of cellular cytotoxicity on two cell lines purchased from American Type Culture Collection (Manassas, VA, USA): normal alpha mouse liver 12 (AML12) and immortalized human embryonic kidney (Hek293) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.

Results and discussion

Colloidal stability, particle diameter, zeta potential, and crystal structure

The GdEu_xTb_1−xO₃@PAA/PDA nanoparticles were labelled as x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1, representing the mole compositions used in the synthesis. The actual compositions (x) were estimated from ICP-AES and EDS analyses (Table 1). The EDS spectra are provided in Fig. S1 (ESI†), confirming the presence of Eu, Gd, and Tb in the nanoparticles. As illustrated in the HRTEM images (Fig. 2a), the particle diameters of the nanoparticles were ultrasmall, ranging from 1 to 3 nm. The average particle diameters (d_avgs) were estimated at 1.8, 2.0, 2.0, 2.2, 2.0, 2.3, and 2.0 nm for x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1, respectively, using log–normal function fits (Fig. 2b & Table 1). Fig. 2c presents the nanoparticle solution and powder sample images. The solution samples remained transparent without nanoparticle precipitation after synthesis (>1 year), demonstrating strong colloidal stability in aqueous media due to the hydrophilic PAA polymer grafting on the nanoparticle surfaces. Despite the photosensitizer PDA, having low water solubility,³⁷ its minor amount during synthesis did not affect colloidal stability. The colloidal dispersion of the nanoparticles in aqueous media was confirmed through laser light scattering, known as the Tyndall effect (Fig. S2 in ESI†). The high negative zeta potentials (ζ < −20 mV) were observed (Fig. 2d & Table 1), confirming their good colloidal stability in aqueous media.

Fig. 2 GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1): (a) HRTEM images, (b) log–normal function fits depicting the observed particle diameter distributions, (c) images of solution samples (top), showing good colloidal stability in aqueous media, and powder samples (bottom), and (d) zeta potential curves and Gaussian function fits.

Table 1 Physicochemical properties of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles

x	ICP-AES (atomic %)			EDS (atomic %)			d avg (nm)	ζ (mV)	S (wt%)	δ (nm^−2)	N PAA ^c
	Gd	Eu	Tb	Gd	Eu	Tb
a Surface-grafting wt% of PAA and PDA, with values in parentheses indicating the wt% relative to GdEuxTb1−xO3 nanoparticles. b Surface-grafting density,^49 representing the average number of PAA polymers covering a nanoparticle unit surface area. c Average number of PAA polymers covering a nanoparticle surface (= δ × πdavg^2).
0	72.7	0	27.3	56.5	0	43.5	1.8	−27.3	67.3 (28.1)	1.8	18
0.1	51.6	5.3	43.1	47.0	6.2	46.8	2.0	−21.9	62.8 (30.4)	1.7	22
0.3	51.2	16.0	32.8	48.2	14.8	37.0	2.0	−32.9	62.1 (26.3)	2.0	25
0.5	50.4	26.6	23.0	47.9	23.6	28.5	2.2	−23.4	63.3 (27.9)	2.1	31
0.7	50.0	36.5	13.5	48.0	33.3	18.7	2.0	−26.9	63.9 (28.8)	1.8	23
0.9	49.4	46.3	4.3	48.3	43.1	8.6	2.3	−34.7	60.4 (27.9)	2.0	34
1	68.0	32.0	0	77.7	22.3	0	2.0	−26.9	69.1 (27.5)	2.0	26

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Eu³⁺, Tb³⁺, and Gd³⁺ can be homogeneously mixed within mixed lanthanide oxide nanoparticles due to their identical cubic crystal structure^38–42 and similar ionic radii.⁴³ The nanoparticles exhibited an amorphous pattern due to their ultrasmall particle diameters (Fig. S3a in ESI†). However, distinct sharp peaks indicative of the cubic structure were observed after TGA owing to the heat treatment⁴⁴ (Fig. S3b in ESI†). The lattice constants after TGA were consistent with mole-percent averaged values of those of individual bulk Ln₂O₃ (Ln = Eu, Gd, and Tb)^38–40 (Table S1 in ESI†), confirming the homogeneous mixing of the different Ln³⁺ within the nanoparticles.

Surface grafting of PAA and PDA on the nanoparticle surfaces

PAA and PDA are grafted on the nanoparticle surfaces through electrostatic interaction between their –COOH groups and the Ln³⁺ ions of the nanoparticles. In addition, the nitrogen of PDA can contribute to the interaction. The binding structure of PAA and PDA is proposed in Fig. 1. Multiple binding between each PAA and a nanoparticle is possible because of ∼27 –COOH groups per PAA and numerous Ln³⁺ ions on each nanoparticle surface. The FT-IR absorption spectra of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1), and their references, including GdEu_xTb_1−xO₃@PAA nanoparticles, PAA, and PDA, are presented in Fig. 3. Before binding to the nanoparticles, the C=O stretching peak of PAA at ∼1700 cm⁻¹ red-shifted and split into COO⁻ antisymmetric stretching vibrations at ∼1548 cm⁻¹ and symmetric stretching vibrations at ∼1396 cm⁻¹ after binding to the nanoparticles^45,46 (Fig. 3). This shift and splitting indicate bidentate⁴⁷ electrostatic (i.e., hard acid-base⁴⁸) binding of COO⁻ groups of PAA to the Ln³⁺ of the nanoparticles. The C=O stretching peak intensity at ∼1700 cm⁻¹ increased after PDA binding to the nanoparticles compared to that before binding (Fig. 3), confirming the successful electrostatic binding of COO⁻ groups of PDA to the Ln³⁺ of the nanoparticles. Key absorption peak frequencies, supporting the successful PAA and PDA grafting on the nanoparticles, are provided in Table S2.†

Fig. 3 FT-IR absorption spectra of PAA, PDA, GdEu_xTb_1−xO₃@PAA nanoparticles (labelled as “no PDA”), and GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (labelled as “PDA”) (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1). Subscripts “AS” and “SS” indicate asymmetric and symmetric stretchings, respectively.

Surface-grafting amount of PAA

The major grafting ligand on the nanoparticle surfaces was PAA, given its larger quantity (1 mmol) compared to PDA (10–50 μmol) used during synthesis. Surface-grafting amounts (S) were determined in wt% from TGA curves. Fig. 4 illustrates mass drops due to water and air desorption between room temperature and ∼110 °C. Afterward, PAA and PDA were removed from the nanoparticles at temperatures up to ∼410 °C due to a combustion reaction with flowing hot air. Estimated grafting amounts for PAA and PDA were ∼63% (Table 1), after accounting for water and air desorption. Then, TGA curves remained flat, indicating remaining mixed lanthanide oxide nanoparticles with a wt.% of ∼28% (Table 1), as confirmed by the crystalline XRD patterns after TGA (Fig. S3 in ESI†). The average number of PAA polymers grafting a nanoparticle unit surface area, i.e., surface-grafting densities (δ),⁴⁹ and the average number (N_PAA) of PAA polymers grafting a nanoparticle surface were estimated to be ∼1.9 nm⁻² and ∼25, respectively (Table 1). These estimates relied on the above-estimated surface-grafting wt% of PAA polymers (excluding minor PDA surface-grafting wt%), d_avgs obtained from HRTEM images, and mole% averaged bulk densities⁵⁰ of different Ln₂O₃ (Ln = Eu, Gd, and Tb).

Fig. 4 TGA curves of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1) under air flow.

Optical properties: colour tuning, excitation and PL spectra, absolute QYs, and emission lifetimes

Colour tuning. The lanthanide ion concentrations used for all optical property measurements are provided in Table S3.† Eu and Tb emit red (616 nm) and green (545 nm) light,^1,2,8 respectively, while Gd is optically transparent in the visible range.⁹Fig. 5a & b show GdEu_xTb_1−xO₃@PAA/PDA nanoparticle solution and powder sample images under 254 nm UV light irradiation, demonstrating colour tuning between green and red with strong emission intensity by varying x from 0 to 1. Additionally, the colour tunability is displayed in the Commission International de I'Eclairagein (CIE) (1931) system^29,31,36 (Fig. 5c) with CIE chromaticity coordinates (a,b) for all values of x listed in Table S4 (ESI†). The approximate colour corresponding to each CIE coordinate (a,b) in Fig. 5c is provided in Table S4.†Fig. 5c shows that the CIE coordinates (a,b) align with previous studies,^29,36 and CIE coordinate ‘b’ varies linearly with ‘a’ as b = 0.77715–0.65297a, consistent with the findings of Qin and Tang.³¹ The CIE coordinates for reddish orange (x = 1; a = 0.6197, b = 0.3706) and yellowish green (x = 0; a = 0.3141, b = 0.5674) of the nanoparticles closely match the red (0.67, 0.33) and green (0.21, 0.71) coordinates of the National Television Standard Committee (NTSC),⁵¹ suggesting the suitability of the nanoparticles for colour display applications. Although not studied here, the GdEu_xTb_1−xO₃@PAA/PDA nanoparticles may also emit visible photons under X-ray irradiation,^52–54 valuable for use as X-ray scintillators in X-ray imaging.

Fig. 5 Images of (a) aqueous solution samples and (b) powder samples of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1) under 254 nm UV irradiation, illustrating the colour tuning between green and red by adjusting x. (c) CIE (1931) chromaticity system, showing the colour tuning between green and red.

Excitation spectra

To determine the excitation wavelengths (λ_ex) for taking PL spectra, excitation spectra of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media (Fig. S4†) were measured using the most intense emission peaks of Tb at 545 nm and Eu at 616 nm as references. The resulting λ_ex values are provided in Table 2. These λ_ex values closely match the strong absorption peaks of PDA at ∼275 nm in its pure and conjugated nanoparticle (x = 0, 1) UV-visible absorption spectra (Fig. S5†). This similarity indicates that PDA, acting as a photosensitizer, efficiently absorbs photons at 260–295 nm and transfers energy to the GdEu_xTb_1−xO₃@PAA/PDA nanoparticles.

Table 2 Optical (λ_ex, absolute QY, and τ) properties, water proton spin relaxivities (r₁ and r₂), and X-ray attenuation efficiency (η) of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1)

x	λ ex (nm)	Absolute QY (%)		τ (ms)		r 1 ^a (s^−1 mM^−1)		r 2 ^a (s^−1 mM^−1)		η (HU mM^−1)
		No PDA	PDA	616 nm peak (Eu)	545 nm peak (Tb)	No. PDA	PDA	No. PDA	PDA	35 kVp	50 kVp	75 kVp
a For r1, r2, and η, total concentration of (Eu + Gd + Tb) was used.
0	290	7.9	35.8	—	1.850	—	—	—	—	12.0	10.0	9.7
0.1	289	5.8	36.2	1.113	1.447	43.4	31.3	95.7	58.6	—	—	—
0.3	289	7.3	34.1	0.700	1.222	45.2	26.1	88.0	48.4	—	—	—
0.5	287	3.8	39.7	0.910	1.369	49.0	34.7	88.0	63.8	—	—	—
0.7	289	2.5	31.2	0.843	1.361	—	—	—	—	—	—	—
0.9	288	2.3	20.0	0.811	1.429	60.8	38.2	95.6	70.6	—	—	—
1	288	6.9	51.6	0.413	—	—	—	—	—	10.8	9.0	9.1

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PL spectra

The PL spectra of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media showed strong emission from Eu³⁺ and Tb³⁺ at the determined λ_exs (Fig. 6). The transition wavelengths and assignments are detailed in Table S5 (ESI†). The peaks exhibited sharp, atomic-like transitions [full widths at half maximum (FWHM) = ∼10 nm] and significant Stokes shifts (>200 nm). These exceptional optical properties contrast with organic dyes with typically broad emission peaks and smaller Stokes shifts (<50 nm). Similarly, QDs exhibit somewhat narrow peak FWHMs (∼20 nm) but smaller Stokes shifts (<50 nm).⁵⁵

Fig. 6 PL spectra of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1) obtained using λ_exs (Table 2).

Absolute QYs

The absolute QYs measured in aqueous media are presented in Table 2. These values are 7 to 10 times higher than those without PDA (Table 2), demonstrating the crucial role of photosensitization for the lanthanides. These QY values are comparable to or higher than those of organic dyes.²⁶

Photoemission lifetimes and energy transfer efficiencies

The photoemission lifetimes (τ_s) of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media were estimated from time-resolved fluorescence (TRF) spectra and by fitting the spectra to an exponential decay function (Fig. 7). The obtained τ values were ∼1 ms (Table 2), significantly 10⁵ to 10⁶ times longer than those of organic dyes (∼10⁻⁹ s)^56,57 and QDs (∼10⁻⁸ s).^56,58 These longer emission lifetimes are highly valuable as they enable background-free signals through time-delayed signal measurements, a capability not achievable with organic dyes and QDs. Note that τ values of Eu³⁺ (x = 0.1 to 0.9) increased with respect to that of x = 1 whereas τ values of Tb³⁺ (x = 0.1 to 0.9) decreased with respect to that of x = 0. This is attributed to the energy transfer from Tb³⁺ to Eu³⁺ in GdEu_xTb_1−xO₃@PAA/PDA nanoparticles.^59–61 The energy transfer efficiency (η_ET) was estimated using the formula η_ET = 1 − (τ_x/τ₀) in which x = 0.1 to 0.9. The estimated η_ET values were ∼0.25, as provided in Table S6† and plotted in Fig. S6.† These appreciable η_ET values indicate an efficient energy transfer between nearby electronic energy levels of Tb³⁺ and Eu³⁺ in the nanoparticles.

Fig. 7 TRF spectra of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1). The λ_ex, λ_em, and τ_Ln (Ln = Eu or Tb) indicate excitation wavelength, emission wavelength, and photoemission lifetime, respectively. The intensity was normalized relative to that at time = 0.

Water proton spin relaxivities

The water proton spin relaxation times and map images were measured before and after the conjugation of PDA to the GdEu_xTb_1−xO₃@PAA nanoparticles. Four samples (i.e., x = 0.1, 0.3, 0.5, and 0.9) were measured since Gd primarily affects water proton spin relaxation due to its very high 4f-electron spin (s = 7/2). Longitudinal (r₁) and transverse (r₂) water proton spin relaxivities were estimated from the slopes of inverse longitudinal (T₁) and transverse (T₂) water proton spin relaxation times plots versus (Eu + Gd + Tb) concentrations (Fig. 8a & b and Table 2). All r₁ and r₂ values were considerably higher than those (4–5 s⁻¹ mM⁻¹) of commercial Gd(III)-chelates for T₁ MRI contrast agents.^10–12R₁ and R₂ map images exhibited clear dose-dependent contrast enhancements (Fig. 8c & d), indicating the potential of GdEu_xTb_1−xO₃@PAA and GdEu_xTb_1−xO₃@PAA/PDA nanoparticles as superior T₁ MRI contrast agents compared to commercial Gd-chelates. These results are owing to a high density of Gd³⁺ (s = 7/2) ions per nanoparticle, combined with good colloidal stability of the nanoparticles. Given that r₂/r₁ ratios are small (<2), the GdEu_xTb_1−xO₃@PAA and GdEu_xTb_1−xO₃@PAA/PDA nanoparticles are better suited as T₁ MRI contrast agents rather than T₂ MRI contrast agents, similar to Gd(III)-chelates.^10–12 The water-attracting capacity of the nanoparticles, and consequently, their r₁ and r₂ values are affected by surface-grafting materials. As shown in Table 2, the r₁ and r₂ values of the GdEu_xTb_1−xO₃@PAA/PDA nanoparticles were lower than those of the GdEu_xTb_1−xO₃@PAA nanoparticles due to PDA being less hydrophilic than PAA, reducing the water-attracting capacity of the nanoparticles.

Fig. 8 Plots of 1/T₁ and 1/T₂ against concentrations (mM) of Eu + Gd + Tb for (a) GdEu_xTb_1−xO₃@PAA nanoparticles and (b) GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media (x = 0.1, 0.3, 0.5, and 0.9). The slopes represent r₁ and r₂ values, respectively. R₁ and R₂ maps with varying Eu + Gd + Tb concentrations (mM) for (c) GdEu_xTb_1−xO₃@PAA nanoparticles and (d) GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media. The values below the maps indicate 1/T₁ (= R₁) and 1/T₂ (= R₂) values (s⁻¹).

X-ray attenuation properties

The X-ray attenuation power increases with increasing atomic number (Z).^7,62,63 Considering that Eu (Z = 63), Gd (Z = 64), and Tb (Z = 65) have similar atomic numbers, two samples of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0 and 1) underwent X-ray phantom image measurements in aqueous media. Additionally, the Ultravist, a commercial iodine (Z = 53)-based CT contrast agent, was measured for comparison. As shown in Fig. 9a, the phantom images of the nanoparticle samples in aqueous media appeared brighter than those of Ultravist at similar atomic concentrations, indicating the superiority of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles over iodine-based CT contrast agents. To demonstrate this quantitatively, the X-ray attenuation power was estimated using the phantom images in Hounsfield units (HU). The formula HU = 1000 (μ_sample − μ_water)/μ_water was used, where μ represents the linear attenuation coefficient of the materials estimated from the phantom images. As illustrated in Fig. 9b, the samples exhibited higher X-ray attenuation power than Ultravist across X-ray source voltages of 35, 50, and 75 kVp. X-ray attenuation efficiencies (η; HU mM⁻¹) were ∼10 HU mM⁻¹ (Table 2), obtained by dividing observed X-ray attenuation power by atomic concentration (53.9 mM [Gd + Tb] and 73.4 mM [Eu + Gd]), ∼2 times higher than those of Ultravist (4.0, 5.3, and 5.9 HU mM⁻¹ at X-ray source voltages of 35, 50, and 75 kVp, respectively, estimated from the slopes in Fig. 9b-i, b-ii, & b-iii). These findings affirm the potential of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles as CT contrast agents.

Fig. 9 (a) X-ray phantom images and (b) X-ray attenuation power plots of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles in aqueous media for x = 0 (53.9 mM [Gd + Tb]) and x = 1 (73.4 mM [Eu + Gd]) at X-ray source voltages of (i) 35, (ii) 50, and (iii) 75 kVp. Water and Ultravist were used as references.

Cell viability

Given that all nanoparticle samples contain Eu, Gd, and Tb, two samples of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0 and 1) underwent MTT cell viability assay. Fig. 10 illustrates that cell viabilities for AML12 and Hek293 cells remained >90% at concentrations of up to 500 μM [Eu + Gd] and [Gd + Tb] for the two samples, indicating low cytotoxicity and thus the suitability of GdEu_xTb_1−xO₃@PAA/PDA nanoparticles for biomedical applications.

Fig. 10 MTT cell viability assay results for AML12 and Hek293 cells following a 48 h incubation with GdEu_xTb_1−xO₃@PAA/PDA nanoparticles [x = (a) 0 and (b) 1].

Conclusions

In summary, GdEu_xTb_1−xO₃@PAA/PDA nanoparticles (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9, and 1) were synthesized with d_avg = ∼2.0 nm. These nanoparticles exhibited colloidal stability (no precipitation in aqueous media for >1 year) and high cell viability (>90%). They demonstrated multiple exceptional properties within a single nanoparticle, suitable for various applications as follows:

1. The nanoparticles can transition between green (545 nm) and red (616 nm) by adjusting x, along with high absolute QYs (>30%) and long emission lifetimes (∼1 ms) in aqueous media. This capability, facilitated by PDA conjugation as a photosensitizer, makes the nanoparticles suitable for optical imaging, noise-free signal detection, and colour display applications.

2. They exhibited r₁ values ∼10 times higher than those of commercial Gd-chelate-based T₁ MRI contrast agents, with small r₂/r₁ ratios (<2), and η values ∼2 times higher than those of commercial iodine-based CT contrast agents, making them suitable as both T₁ MRI and CT contrast agents.

Author contributions

D. Z., Y. L. and S. L. H. conceptualized the work and performed the preparation and characterization of the nanoparticles. T. T. and A. K. A. A. S analyzed data. H. L. measured water proton spin relaxivities and map images. D. A. and H. N. measured cell viability. J. A. P. and J.-u. Y. measured X-ray attenuation power. W.-S. C. measured PL spectra and QYs. Y. C. and G. H. L. drafted the manuscript. All authors have approved the final version of the manuscript.

Data availability

The raw data required to reproduce these findings will be made available upon request sent directly to the corresponding author.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by the Basic Science Research Program of the National Research Foundation (NRF) funded by the Korea government (Ministry of Science, and Information and Communications Technology: MSIT) (Basic Research Laboratory, No. 2021R1A4A1029433).

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Footnote

† Electronic supplementary information (ESI) available: EDS spectra, laser light scattering images, XRD patterns and analyzed data, excitation spectra, UV-visible absorption spectrum, FT-IR absorption peak assignments, CIE (1931) chromaticity coordinates, and PL peak assignments. See DOI: https://doi.org/10.1039/d4nr02195a

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