Dual-Activator Codoped Upconversion Nanoprobe with Core–Multishell Structure for in Vitro and in Vivo Detection of Hydroxyl Radical

Abstract

Monitoring the fluctuation of hydroxyl radical (·OH) in the body can serve as an effective tool for the prediction of relative diseases; however, it is highly challenging due to the radical's short lifetime, high reactivity, and extremely low concentration. Sandwich structured lanthanide-doped upconversion nanoparticles (UCNPs) exhibit unique luminescence properties and great prospects in bioimaging. Nonetheless, their rather low luminescence efficiency and intensity are serious limitations for their application. Herein, we report on dual-activator codoped UCNPs with a core-multishell structure that greatly improve the luminescence intensity and lifetime by 46-fold and 2.6-fold, respectively, compared to those of the monoactivator doped sandwich structured UCNPs. Moreover, emitting ions in the designed core-multishell (CMS)-UCNPs were confined in a homogeneous and thin shell layer (∼2 nm); thus, the luminescence resonance energy transfer (LRET)-based CMS-UCNPs@azo dye nanoprobe exhibited a largely shortened energy transfer distance and a pronounced luminescence quenching yield (97%), affording the nearly zero background signal and achieving an ultrahigh sensitivity for the detection of ·OH (with limit of quantitation (LOQ) of 0.10 fM). With good biocompatibility, low biotoxicity, and enhanced luminescence intensity and lifetime, the developed nanoprobe was competent in monitoring the subtle fluctuation of ·OH concentration both in vitro and in vivo.

Recent Advances in Luminescence Imaging of Biological Systems Using Lanthanide(III) Luminescent Complexes

“…Systems capable of executing multiple functions, also called multimodal systems, are desirable due to the possibility of obtaining more information using a single system [113][114][115]. For example, NPs functionalized with the [Eu(aa) 2 (dta)(phen)] complex can be used not only in luminescence imaging but also in X-ray computed tomography imaging (CT) due to the high X-ray absorption cross-section of Eu III [116].…”

“…In the UC process through ESA, a sensitizer ion absorbs low-energy photons, followed by energy transfer to the activator ion, which then emits in a characteristic wavelength. Yb III /Er III [173][174][175][176], Yb III /Tm III [113,114], and Nd III /Yb III /Er III [177,178] are some of the most common sensitizer/activator systems. The challenge in developing molecular UC systems is to overcome the high non-radiative rates caused by vibrational coupling with O-H and C-H vibrations, inefficient 4f -4f excitation of the sensitizer ion, and long distances activator-sensitizer in Ln III complexes that lower the energy transfer rates [43].…”

Construction of Multicolor Upconversion Nanotheranostic Agent for in-situ Cooperative Photodynamic Therapy for Deep-Seated Malignant Tumors

“…The molar ratio of lanthanide ions was Y:Yb:Tm:Ho = 54.5:40:0.5:5. Then, UCNPs with a NaYF 4 @NaYF 4 :Yb,Tm,Ho@NaYF 4 structure were prepared via the layer-by-layer seed-mediated shell growth strategy (Song et al, 2017(Song et al, , 2018. Firstly, to prepare the NaYF 4 SCHEME 1 | Schematic image for the synthetic procedure of the UCNPs@SiO 2 /HA/MB/ICG@PEG-TPP nanotheranostic agent and its theranostic functions for the photodynamic therapy.…”

Opportunities for Persistent Luminescent Nanoparticles in Luminescence Imaging of Biological Systems and Photodynamic Therapy

“…Thus, luminescence imaging of biological systems is based on exciting a volume of a sample containing a luminescent compound using an adequate excitation source and wavelength and collecting the light emitted. Luminescence imaging is a sensitive technique that allows diagnosing diseases [ 15 , 16 , 17 ], reconstructing 3-D structures of tissues or cellular components [ 18 , 19 ], sensing chemical species [ 1 , 2 , 3 , 12 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], and unraveling cellular processes [ 39 , 40 , 41 ]. One of the drawbacks of this technique is the strong background emission intensity, especially in the blue and green regions of the electromagnetic spectrum that are often higher than those of the luminescent compound.…”

“…Nanomaterials 2020, 10, x FOR PEER REVIEW 2 of 37 reconstructing 3-D structures of tissues or cellular components [18,19], sensing chemical species [1][2][3]12,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], and unraveling cellular processes [39][40][41]. One of the drawbacks of this technique is the strong background emission intensity, especially in the blue and green regions of the electromagnetic spectrum that are often higher than those of the luminescent compound.…”