High Quantum Yields and Biomedical Fluorescent Imaging Applications of Photosensitized Trivalent Lanthanide Ion-Based Nanoparticles

Abstract

In recent years, significant advances in enhancing the quantum yield (QY) of trivalent lanthanide (Ln³⁺) ion-based nanoparticles have been achieved through photosensitization, using host matrices or capping organic ligands as photosensitizers to absorb incoming photons and transfer energy to the Ln³⁺ ions. The Ln³⁺ ion-based nanoparticles possess several excellent fluorescent properties, such as nearly constant transition energies, atomic-like sharp transitions, long emission lifetimes, large Stokes shifts, high photostability, and resistance to photobleaching; these properties make them more promising candidates as next-generation fluorescence probes in the visible region, compared with other traditional materials such as organic dyes and quantum dots. However, their QYs are generally low and thus need to be improved to facilitate and extend their applications. Considerable efforts have been made to improve the QYs of Ln³⁺ ion-based nanoparticles through photosensitization. These efforts include the doping of Ln³⁺ ions into host matrices or capping the nanoparticles with organic ligands. Among the Ln³⁺ ion-based nanoparticles investigated in previous studies, this review focuses on those containing Eu³⁺, Tb³⁺, and Dy³⁺ ions with red, green, and yellow emission colors, respectively. The emission intensities of Eu³⁺ and Tb³⁺ ions are stronger than those of other Ln³⁺ ions; therefore, the majority of the reported studies focused on Eu³⁺ and Tb³⁺ ion-based nanoparticles. This review discusses the principles of photosensitization, several examples of photosensitized Ln³⁺ ion-based nanoparticles, and in vitro and in vivo biomedical fluorescent imaging (FI) applications. This information provides valuable insight into the development of Ln³⁺ ion-based nanoparticles with high QYs through photosensitization, with future potential applications in biomedical FI.

Keywords: Ln3+ ion-based nanoparticle; biomedical fluorescent imaging application; high quantum yield; host matrix; organic ligand; photosensitization.

Scheme 1

Two types of strategies to enhance QYs: (a) doping of Ln³⁺ ions into photosensitizing host matrix (co-doping elements further enhance QYs) and (b) capping of Ln³⁺-containing nanoparticles with photosensitizing organic ligands.

Figure 1

Potential application areas of photosensitized Ln³⁺ ion-based nanoparticles (Ln = Eu, Tb, and Dy) with high QYs in biomedical FI. TEM image and fluorescent samples taken from [18].

Figure 2

Diagrams showing energy transfer (a) from host matrix (i.e., NBO₄³⁻) to Tb³⁺ and Eu³⁺ ions and from Tb³⁺ to Eu³⁺ ions [110], (b) from Ce³⁺ to Tb³⁺ ions and from Tb³⁺ to Eu³⁺ ions [57], and (c) from organic ligands to excited (Ln³⁺)* ions: the right panel shows the fluorescent quenching via nonradiative energy transfer from excited (Ln³⁺)* ions to conjugated functional groups (OH, CH, and NH) of solvent or organic molecules [112]. (d) Schematic diagram of core–shell structure for QY enhancement through surface passivation of the core nanoparticle with the shell.

Figure 3

(a) TEM image at 2 nm scale. (b) Schematic illustration of bonding structure of PAA and PDA on ultrasmall Ln₂O₃ (Ln = Eu, Tb, or Dy) nanoparticle surface. (c) Photographs of water and PAA/PDA–Ln₂O₃ (Ln = Eu, Tb, or Dy) nanoparticle colloids in aqueous media (I) before and (II) under 254 nm UV irradiation, showing stable colloids in aqueous media along with strong red and green emissions for Ln = Eu and Tb, respectively, as well as pale-yellow emissions for Ln = Dy. (d) Concentration-normalized PL spectra of PAA/PDA–Ln₂O₃ (Ln = Eu, Tb, and Dy) nanoparticle colloids in aqueous media, with excitation wavelengths (λ_exs) of 287, 286, and 285 nm, respectively [18].

Figure 4

(a) TEM image of as-prepared Y_0.6VO₄:Eu_0.4³⁺ nanoparticles at 100 nm scale. (b) PL spectra of Y_1−xVO₄:Eu_x³⁺ nanoparticles at various Eu³⁺ ion-doping concentrations (x = 0.01, 0.025, 0.05, 0.1, 0.15, 0.25, 0.4, 0.5, and 0.6) (λ_ex = 310 nm). (c) PLQYs (left) and PL lifetimes (right) of Y_1−xVO₄:Eu_x³⁺ nanoparticles as a function of Eu³⁺ ion-doping concentration; the inset shows photographs of the nanoparticle powder samples (x = 0.01, 0.05, 0.1, 0.25, 0.4, and 0.5) under 254 nm UV irradiation [70].

Figure 5

(a) TEM image at 20 nm scale and (b) particle diameter distribution of Eu³⁺ ion-doped CaMoO₄ nanoparticles. (c) PLQYs (left) and PL lifetimes (right) of Eu³⁺ ion-doped CaMoO₄ nanoparticles as a function of Eu/Ca ratio. (d) PL spectra of Eu³⁺ ion-doped CaMoO₄ nanoparticles at various Eu/Ca ratios (λ_ex = 280 nm) [72].

Figure 6

(a) TEM image of Y_1.9O₃:Eu_0.1³⁺ nanoparticles at 10 nm scale. The inset shows a magnified TEM image at 2 nm scale, displaying lattice fringes with a lattice distance of 0.306 nm for the (222) plane. (b) Particle diameter distribution obtained from dynamic light scattering for Y_1.9O₃:Eu_0.1³⁺ nanoparticles dispersed in deionized water. The inset shows photographs of Y_1.9O₃:Eu_0.1³⁺ nanoparticle colloids in aqueous media with (left) and without (right) 254 nm UV irradiation. (c) PL spectrum of Y_1.9O₃:Eu_0.1³⁺ nanoparticles recorded using 246 nm excitation. The inset shows the CIE color coordinates of red emission (x = 0.5941, y = 0.3039). (d) Time-resolved fluorescent spectrum and double-exponential fitting using lifetime parameters (τ₁ and τ₂) [73].

Figure 7

(a) TEM image of as-prepared La_0.4PO₄:Ce_0.1³⁺,Tb_0.5³⁺ nanoparticles at 5.0 nm scale. The inset shows a magnified TEM image, displaying the lattice distance of 0.276 nm for the (102) plane. (b) Excitation and (c) PL spectra of La_1−0.1−xPO₄:Ce_0.1³⁺,Tb_x³⁺ nanoparticles with different Tb³⁺ ion-doping concentrations (i.e., x = 0.3, 0.4, 0.5, 0.6, and 0.7). The inset in PL spectra shows magnified PL spectra between 320 and 400 nm. (d) PLQYs (left) and PL lifetimes (right) of La_1−0.1−xPO₄:Ce_0.1³⁺,Tb_x³⁺ nanoparticles as a function of Tb³⁺ ion-doping concentrations (i.e., x = 0.3, 0.4, 0.5, 0.6, and 0.7). The inset shows photographs of La_1−0.1−xPO₄:Ce_0.1³⁺,Tb_x³⁺ nanoparticles under 254 nm UV irradiation [33].

Figure 8

(a) TEM image of NaY_{0. 4}F_4:Ce³⁺_0.2,Tb³⁺_0.4 nanoparticles at 20 nm scale. (b) Excitation and (c) PL spectra of NaY_1−0.2−xF₄:Ce³⁺_0.2,Tb³⁺_x nanoparticles (x = 0.2, 0.3, 0.4, 0.5, and 0.6). (d) PLQYs (left) and PL lifetimes (right) of NaY_1−0.2−xF₄:Ce³⁺_0.2,Tb³⁺_x nanoparticles (x = 0.2, 0.3, 0.4, 0.5, and 0.6); the inset shows photographs of NaY_1−0.2−xF₄:Ce³⁺_0.2,Tb³⁺_x nanoparticles (x = 0.2, 0.3, 0.4, 0.5, and 0.6) under 254 nm UV irradiation [36].

Figure 9

(a) (I) TEM image and (II) magnified TEM image of S-LTbH:Gd at 200 nm scales. (b) PL spectra of (i) NO₃-LTbH, (ii) NO₃-LTbH: Gd, (iii) S-LTbH, and (iv) S-LTbH: Gd [85]. The inset shows photographs of samples under 254 nm UV irradiation.

Figure 10

(a) TEM image of Gd₂O₃:Dy³⁺ nanoparticles annealed at 600 °C at 50 nm scale. (b) Excitation spectra of Gd₂O₃:Dy³⁺ nanoparticles prepared at annealing temperatures of 600, 700, and 800 °C with a monitoring emission wavelength of 572 nm. (c) PL spectra of Gd₂O₃:Dy³⁺ nanoparticles prepared at different annealing temperatures at an excitation wavelength of 274 nm. The inset shows magnified PL spectra between 650 and 700 nm. (d) CIE plot of Gd₂O₃:Dy³⁺ nanoparticles prepared at different annealing temperatures (600, 700, and 800 °C) [46].

Figure 11

(a) TEM image of YVO₄:2Dy nanoparticles annealed at 500 °C at 20 nm scale: the inset displays a magnified TEM image, showing the lattice distance of 0.157 nm for the (004) plane. (b) Excitation spectra of YVO₄:2Dy nanoparticles monitored at 574 nm without and with annealing at temperatures of 500 and 900 °C. (c) PL spectra of YVO₄:2Dy nanoparticles at 320 nm excitation wavelength without and with annealing at temperatures of 500 and 900 °C. (d) PL spectra at 320 nm excitation of Ba²⁺ ion co-doped YVO₄:2Dy nanoparticles with different Ba²⁺ ion concentrations annealed at 900 °C [45].

Figure 12

(a) TEM image of GdVO₄:Eu³⁺/Tb(BA)₃Phen sub-microflowers at 200 nm scale. (b) PL spectra of GdVO₄:Eu³⁺/Tb(BA)₃Phen at various Tb³⁺ ion concentrations (A1 = 0, A2 = 0.1, A3 = 0.2, A4 = 0.4, A5 = 0.6, A6 = 0.8, and A7 = 1.0 mmol) under 290 nm excitation. (c) Digital camera photographs of fluorescent samples under 254 nm UV irradiation [55]. (d) PL spectra of Y_1.9−yO₃:Eu³⁺_0.1,Tb³⁺_y nanoparticles (y = 0.0015, 0.0025, 0.005, and 0.01). The inset shows the variation in PL intensity with changing y values [57].

Figure 13

Fluorescence images of Giardia lamblia stained with SA-labeled nanoparticles (a-I) without and (a-II) with time delay (100 μs). The excitation wavelength was 380–420 nm. Scale bars: 10 µm [12]. (b) TG fluorescence microscopy images of HeLa cells incubated with photosensitized Tb-NPs for 24 h at different concentrations (shown on the top of Figure 13). The time delay was 10 μs. Scale bars: 10 μm [13]. DIC: differential interference contrast imaging mode in optical microscope. (c) In vitro FI of CNE2 cells incubated with Gd₂O₃:1%Dy³⁺ nanoparticles: (c-I,c-III) bright field images and (c-II,c-IV) fluorescence images captured using blue and yellow filters, respectively. Scale bars: 50 μm for (c-I,c-II), and 20 μm for (c-III,c-IV) [166].

Figure 14

In vivo fluorescence imaging of HAP:Eu/Gd (2:1.5) nanosheets in BALB/c-nu mice: (a) before and (b) 10 min after IP injection, displaying a distinct fluorescent signal (red-orange) in enterocoelia. The arrows indicate signal intensity enhancement [167]. In vivo tumor imaging of ⁸⁹Zr-uEuNP@PET on CT26 tumor-bearing mice: (c) 48 h tumor site ROI measurement spectrum vs. the regular Cerenkov spectrum and (d) 48 h Cerenkov imaging postinjection under 620 nm filter [164].

Figure 15

(a) In vitro cell viability of PAA/PDA–Ln₂O₃ (Ln = Eu, Tb, or Dy) nanoparticles in AML12 and HEK293 cells after 48 h of incubation, exhibiting nearly no cellular toxicity [18]. (b) Cell viability of PEG–TbNRs in N13 cells after 24 h of incubation, exhibiting no cellular toxicity [134]. (c) Hematoxylin and eosin-stained tissue sections harvested from mice before and 7 days after injection of Ir-Eu-MSN. No noticeable abnormality was observed in various organs such as the liver, spleen, heart, lung, and kidneys [9].

Figure 16

CSM images of PC-3 cells incubated with DOTA-GdVO4:4%Eu-DGEA NSs (labeled as Target, a1–a3) and DOTA-GdVO4:4%Eu (labeled as Control, b1–b3) with the concentration of 200 mg/mL for 4 h (scale bar = 20 μm). Eu red emission (λ_ex = 488 nm). DAPI blue emission (λ_ex = 405 nm) [180]. Scale bars: 20 μm.

Figure 17

In vivo PL imaging of mice after subcutaneous injection (a) without and (b) with EuGd-MSNs (Eu³⁺:Gd³⁺ = 1:1) at an excitation wavelength of 430 nm. Red circles indicate tumor. (c) Tumor growth curves for HeLa tumor cell-bearing mice from 0 to 23 days; error bars were determined using 3 mice in each group [187].

Figure 17

In vivo PL imaging of mice after subcutaneous injection (a) without and (b) with EuGd-MSNs (Eu³⁺:Gd³⁺ = 1:1) at an excitation wavelength of 430 nm. Red circles indicate tumor. (c) Tumor growth curves for HeLa tumor cell-bearing mice from 0 to 23 days; error bars were determined using 3 mice in each group [187].