Biocompatible Upconverting Nanoprobes for Dual-Modal Imaging and Temperature Sensing

Abstract

The demand for multimodal nanomaterials has intensified in recent years driven by the need for ultrasensitive bioimaging probes and accurate temperature monitoring in biological objects. Among the different multimodal nanomaterials that have been extensively studied in the past decade, upconverting nanoparticles are among the most promising. In this paper, we report the synthesis of upconverting nanoparticles with complex core-shell compositions, capable of being excited by 808 or 980 nm laser irradiation and exhibiting a good MRI response. The synthesized nanoparticles also demonstrated high colloidal stability in both aqueous and biological media as well as temperature-sensing capabilities, including the physiological range. Furthermore, the upconversion nanoparticles exhibited significantly lower cytotoxicity for HEK293T cells than the commercially available MRI contrast agent Gd-DTPA.

Figure 1

Schematic illustration of UCNPs synthesis via a coprecipitation method (a). Powder XRD patterns (b) of reference (PDF ICDD 00-027-0699), NaGdF₄:Yb,Er (core) (1), NaGdF₄:Yb,Er@NaGdF₄:Yb (core–shell) (2), and NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd (core–shell) UCNPs (3). SEM and TEM images of NaGdF₄:Yb,Er (c,f), NaGdF₄:Yb,Er@NaGdF₄:Yb (d,g), and NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd NPs (e,h). High-resolution TEM images of NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd UCNPs (i,j) showing different interplanar distances. FT-IR spectra of NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd UCNPs before and after ligand removal (k). Particle size distribution (PSD) (from DLS measurements) of NaGdF₄:Yb,Er (l), NaGdF₄:Yb,Er@NaGdF₄:Yb (m), and NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd UCNPs (n) suspended in DI water.

Figure 2

Simplified energy-level diagram of Yb³⁺ and Er³⁺ (a); emission spectra of UCNPs (core or core–shell with different compositions) dispersed in cyclohexane (b); PL decay curves with calculated UC emission rise time (τ_r) and UC lifetime (τ) values for different emission transitions: ⁴G_11/2 → ⁴I_15/2 (c), ²H_9/2 → ⁴I_15/2 (d), ²H_11/2 → ⁴I_15/2 (e), ⁴S_3/2 → ⁴I_15/2 (f), and ⁴F_9/2 → ⁴I_15/2 (g).

Figure 3

Energy-level scheme and optical transitions of Nd³⁺, Yb³⁺, and Er³⁺ (a); emission spectra of NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd core–shell UCNPs in the visible and NIR regions (b); PL decay curves with calculated UC emission rise time and UC emission lifetime values for different emission transitions: ⁴G_11/2 → ⁴I_15/2 (c), ²H_9/2 → ⁴I_15/2 (d), ²H_11/2 → ⁴I_15/2 (e), ⁴S_3/2 → ⁴I_15/2 (f), ⁴F_9/2 → ⁴I_15/2 (g), and ²F_5/2 → ²F_7/2 (Yb³⁺) (h) of UCNPs dispersed in DI water or cyclohexane under 808 nm laser excitation.

Figure 4

Zeta potential of ligand-free NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd UCNPs in water as a function of pH (a) and colloidal stability of NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd UCNPs in DI water and DMEM media supplemented with 10% FBS evaluated as change of emission (λ_em = 539.5 nm) intensity in time (b).

Figure 5

Temperature-dependent emission spectra (λ_ex = 808 nm laser) of NaGdF₄:Yb,Er@NaGdF₄:Yb,Nd (a) and emission intensity contour plot (range 510–545 nm) as a function of temperature (b). Logarithmic ratio of sum intensity of ²H_11/2 → ⁴I_15/2 and ⁴S_3/2 → ⁴I_15/2 emission transitions as a function of 1/T (c); relative (S_r, blue dots) and absolute (S_a, red line) sensitivity as a function of temperature (d).

Figure 6

Viability of HEK 293T kidney cells exposed to different concentrations of UCNPs and the commercial MRI contrast agent Gd-DTPA (a); MRI signal intensity greyscale comparison of commercial gadolinium complex (Gd-DTPA) and UCNPs with different architectures and compositions at various concentrations (b); longitudinal T₁w (c) and transverse T₂w (d) MRI intensity as a function of NPs concentration (μg/mL); longitudinal (1/T₁) (e) and transverse (1/T₂) (f) relaxivity plotted as a function of molar Gd³⁺ concentration. The slopes in parts (e) and (f) represent the molar relaxivities of the UCNPs and Gd-DTPA, respectively. Please note that the black color in the grayscale images represents the MRI response of pure DI water at 37 °C.