Excited Upconversion Nanoparticles Research Articles

A homogeneous biosensor for carbohydrate antigen 153 detection in human serum based on upconversion fluorescence resonance energy transfer

Quantitative determination of carbohydrate antigen 153 (CA153) in human serum plays an important role in early diagnosis of breast cancer. In this work, a highly sensitive and selective biosensor for CA153 detection was developed based on a fluorescent resonance energy transfer (FRET) strategy, in which near-infrared (NIR)-excitable upconversion nanoparticles (UCNPs) and the commercial organic dye, FAM, were employed as energy donor and energy acceptor, respectively. The two components were linked by a molecular beacon (MB) containing CA153 aptamer sequence and the upconversion fluorescence (UCF) of UCNPs can be effectively quenched by FAM. In presence of CA153, the hairpin structure was opened, resulting in the separation of UCNPs and FAM and the inhibition of FRET. The UCF showed a linear relationship with the logarithm of CA153 concentration in the range from 0.01 to 150 U/mL, with a LOD of 4.5 mU/mL in HEPES buffer. This probe can be successfully applied for CA153 assay in human serum, which may be a useful tool for early diagnosis of breast cancer.

Near-infrared manipulation of multiple neuronal populations via trichromatic upconversion

Using multi-color visible lights for independent optogenetic manipulation of multiple neuronal populations offers the ability for sophisticated brain functions and behavior dissection. To mitigate invasive fiber insertion, infrared light excitable upconversion nanoparticles (UCNPs) with deep tissue penetration have been implemented in optogenetics. However, due to the chromatic crosstalk induced by the multiple emission peaks, conventional UCNPs or their mixture cannot independently activate multiple targeted neuronal populations. Here, we report NIR multi-color optogenetics by the well-designed trichromatic UCNPs with excitation-specific luminescence. The blue, green and red color emissions can be separately tuned by switching excitation wavelength to match respective spectral profiles of optogenetic proteins ChR2, C1V1 and ChrimsonR, which enables selective activation of three distinct neuronal populations. Such stimulation with tunable intensity can not only activate distinct neuronal populations selectively, but also achieve transcranial selective modulation of the motion behavior of awake-mice, which opens up a possibility of multi-color upconversion optogenetics.

Observation of split evanescent field distributions in tapered multicore fibers for multiline nanoparticle trapping and microsensing.

The optical attractive force in tapered single-mode fibers (SMFs) is usually uniformly distributed around the tapered section and has been found to be important for trapping and manipulating targeted atoms and nanoparticles. In contrast, a peculiar phenomenon of the evanescent field splitting along the azimuth axis can be experimentally observed by tapering a weakly-coupled MCF into a strongly-coupled MCF to generate supermode interference. Moreover, the supermode interference produces a hexagonally distributed evanescent field and its six vertices give rise to the multiline optical attractive force. For such spectral resonances, the optimum extinction ratio for the transmission dips is given by 47.4 dB, this being determined using an index liquid to cover the tapered MCF. The resonant dips move to a greater extent at longer wavelengths, with the optimum tuning efficiency of 392 nm/RIU for index sensing. The split evanescent fields respectively attract the excited upconversion nanoparticles in the liquid to be linearly aligned and running down the tapered region over the fiber surface, emitting green light with 60° symmetry. The charged nanoparticles were periodically self-organized, with a period of around 1.53 µm. The parallel lines, with 60° rotational symmetry, can be useful for (1) indicating the exact locations of the side-cores or orientations of the tapered MCF; (2) as precision alignment keys for micro-optical manipulation; and (3) enhancing the upconversion light, or for use in lasers, coupling back to the MCF. The split evanescent fields can be promising for developing new evanescent field-based active and passive fiber components with nano-structures.

Independent Luminescent Lifetime and Intensity Tuning of Upconversion Nanoparticles by Gradient Doping for Multiplexed Encoding.

Luminescent materials with engineered optical properties have been developed for multiplexed labeling detection, where encoding capacity plays a pivotal role in the efficiency. However, multi-dimensional optical identities are usually not independent which essentially hinder the practical encoding numbers to access theoretical capacity. In this work, we carefully studied the sensitizer gradient doping structure in near-infrared (NIR) excitable upconversion nanoparticles (UCNPs) and managed to achieve independent emission intensity and lifetime tuning. With the orthogonally tunability, it breaks the constraint of intensity (k) and lifetime (n) correlation and expands the practical encoding number to theoretical value as (k+1)n -1 in binary encoding. This method can also be combined with previous lifetime engineering as well to realize high level multiplexing.

Independent Luminescent Lifetime and Intensity Tuning of Upconversion Nanoparticles by Gradient Doping for Multiplexed Encoding

AbstractLuminescent materials with engineered optical properties have been developed for multiplexed labeling detection, where encoding capacity plays a pivotal role in the efficiency. However, multi‐dimensional optical identities are usually not independent which essentially hinder the practical encoding numbers to access theoretical capacity. In this work, we carefully studied the sensitizer gradient doping structure in near‐infrared (NIR) excitable upconversion nanoparticles (UCNPs) and managed to achieve independent emission intensity and lifetime tuning. With the orthogonally tunability, it breaks the constraint of intensity (k) and lifetime (n) correlation and expands the practical encoding number to theoretical value as (k+1)n−1 in binary encoding. This method can also be combined with previous lifetime engineering as well to realize high level multiplexing.

An aptamer biosensor for CA125 quantification in human serum based on upconversion luminescence resonance energy transfer

CA125 is the most widely used biomarker for the early detection of ovarian cancer. Luminescence resonance energy transfer (LRET)-based probes show pronounced specificity and simplicity for CA125 detection, but they suffer from strong interference from autofluorescence of biosamples. To resolve this problem, near-infrared (NIR)-excitable upconversion nanoparticles (UCNPs) was employed as energy donor to fabricate CA125 biosensor. Carbon dots (CDs) were utilized as energy acceptor for the overlap between the upconversion luminescence (UCL) spectrum of UCNPs and the absorption spectrum of CDs. Aptamer-modified UCNPs were combined with CDs through π-π stacking interaction, which triggered the LRET process and induce UCL quenching with a high quenching efficiency of up to 90%. In presence of CA125, the formation of CA125-aptamer complex blocked the π-π stacking and recovered UCL. The UCL intensity increased linearly with the logarithm of CA125 concentration in the range from 0.01 to 100 U·mL−1. A detection limit of 9.0 × 10−3 U·mL−1 was obtained. This probe is also available for CA125 detection in human serum and may be a useful tool for the early detection of ovarian cancer.

In Vitro Imaging of Animal Tissue with Upconversion Nanoparticles (UCNPs) as a Molecular Probing Agent Using Swept Source Optical Coherence Tomography (SSOCT)

The aim of the current study is to demonstrate the potential of rare earth (RE) based upconversion nanoparticles (UCNPs) as molecular probing agents for non-invasive depth-resolved bioimaging technique, swept-source optical coherence tomography (SSOCT). The Na+ doped La2O3:Er3+/Yb3+ UCNPs were synthesized using a solution combustion route with characterization for emission spectra and morphological study. A custom made SSOCT system was also incorporated for tissue imaging with an A-scan rate of 100 kHz/s, the central wavelength of 1060 nm, an axial and lateral resolution of ~ 4.5 µm and ~ 13 µm in tissue, respectively. UCNPs are utilized as exogenous molecular probing agents to improve local scattering in inner tissue layers. In vitro imaging of chicken breast tissue is functioned with and without excited UCNPs. Time-dependent dynamic changes in scattering coefficients of local tissue and contrast to noise ratio (OCT B-scans) is presented with a new mathematical model. Substantial enhancement in OCT image contrast, local scattering coefficients, and depth range of OCT was observed. The penetration dynamics of excited and non-excited UCNPs with time is reported. Excitation of the UCNPs enhance the scattering coefficients which lead to high contrast OCT images. It also enables the tunable characteristics of UCNPs as targeted molecular probes.

Hydrogenated Titanium Oxide Decorated Upconversion Nanoparticles: Facile Laser Modified Synthesis and 808 nm Near-Infrared Light Triggered Phototherapy

With multiphoton excited upconversion nanoparticles (UCNPs) as energy transducer, ultraviolet (UV) light responsive titanium dioxide (TiO2) can be triggered indirectly by near-infrared (NIR) light for deep-tissue photodynamic therapy (PDT) through the fluorescence resonance energy transfer (FRET) strategy. Compared to pristine TiO2, absorption of hydrogenated black TiO2 (H-TiO2) in visible (vis) and NIR regions presents a marked improvement in performance, which leads H-TiO2 to enhance its overall activity. Owing to the light absorption enhancement, the single component H-TiO2 can be served as vis-driven photosensitizers (PSs) for PDT as well as NIR-triggered photothermal agents (PTAs) for photothermal therapy (PTT) simultaneously. Herein, H-TiO2 decorated Nd3+-sensitized-UCNPs (Nd:UCNPs@H-TiO2) nanocomposites (NCs) were synthesized by Nd:Y3Al5O12 (Nd:YAG) pulsed-laser irradiation of Nd:UCNPs@TiO2 precursors in suspended aqueous solution. Pulsed-laser modified synthesis is the optimum selection for prepar...

Optical Temperature Sensing With Infrared Excited Upconversion Nanoparticles.

Upconversion Nanoparticles (UCNPs) enable direct measurement of the local temperature with high temporal and thermal resolution and sensitivity. Current studies focusing on small animals and cellular systems, based on continuous wave (CW) infrared excitation sources, typically lead to localized thermal heating. However, the effects of upconversion bioimaging at the molecular scale, where higher infrared intensities under a tightly focused excitation beam, coupled with pulsed excitation to provide higher peak powers, is not well understood. We report on the feasibility of 800 and 980 nm excited UCNPs in thermal sensing under pulsed excitation. The UCNPs report temperature ratiometrically with sensitivities in the 1 × 10−4 K−1 range under both excitation wavelengths. Our optical measurements show a ln(I525/I545) vs. 1/T dependence for both 800 nm and 980 nm excitations. Despite widespread evidence promoting the benefits of 800 nm over 980 nm CW excitation in avoiding thermal heating in biological imaging, in contrary, we find that given the pulsed laser intensities appropriate for single particle imaging, at both 800 and 980 nm, that there is no significant local heating in air and in water. Finally, in order to confirm the applicability of infrared imaging at excitation intensities compatible with single nanoparticle tracking, DNA tightropes were exposed to pulsed infrared excitations at 800 and 980 nm. Our results show no appreciable change in the viability of DNA over time when exposed to either wavelengths. Our studies provide evidence for the feasibility of exploring protein-DNA interactions at the single molecule scale, using UCNPs as a reporter.

Enhanced red emission of 808 nm excited upconversion nanoparticles by optimizing the composition of shell for efficient generation of singlet oxygen

With the aim to enhance the upconversion luminescence (UCL) intensity, much attention was paid to reduce the energy-back transfer from Er3+ ions to Nd3+ ions by constructing various kinds of multilayer upconversion nanoparticles (UCNPs). However, the energy-back transfer was difficult to be completely eliminated. Also, the thick shell of multilayer UCNPs is not favourable for effective Förster resonance energy transfer (FRET) in photodynamic therapy (PDT) system. Herein, an effective and facile method was applied to prepare UCNPs by optimizing the composition to largely enhance the red emission (at 660 nm) for efficient generation of singlet oxygen (1O2). In detail, the concentrations of Nd3+ ions and Yb3+ ions doped in the sensitizing shell were systematically researched to balance the energy back-transfer and the light harvest ability. The optimal emission and a relatively high Red/Green (R/G) ratio of NaYF4:Yb,Er,Nd@NaYF4:Yb0.1Nd0.2 UCNPs were obtained simultaneously. Furthermore, the emission under 980 nm excitation demonstrated the energy back-transfer from Er3+ to Yb3+ ions was also notable which was largely ignored previously. Then, UCNPs were encapsulated into mesoporous silica shell, and the photosensitizer Chlorin e6 (Ce6) was covalently conjugated to form a non-leaking nanoplatform. The efficiency of 1O2 generation obviously increased with the enhanced emission of UCNPs.

Emerging ≈800 nm Excited Lanthanide-Doped Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles can tune near-infrared light to visible or even ultra-violet light in emissions. Due to their unique photophysical and photochemical properties, as well as their promising bioapplications, there has been a great deal of enthusiastic research performed to study the properties of lanthanide-doped upconversion nanoparticles in the past few years. Despite the considerable progress in this area, numerous challenges associated with the nanoparticles, such as a low upconversion efficiency, limited host materials, and a confined excitation wavelength, still remain, thus hindering further development with respect to their applications and in fundamental science. Recently, innovative strategies that utilize alternative sensitizers have been designed in order to engineer the excitation wavelengths of upconversion nanoparticles. Here, focusing on the excitation wavelength at ≈800 nm, recent advances in the design, property tuning, and applications of ≈800 nm excited upconversion nanoparticles are summarized. Benefiting from the unique features of ≈800 nm light, including deep tissue penetration depth and low photothermal effect, the ≈800 nm excited upconversion nanoparticles exhibit superior potential for biosensing, bioimaging, drug delivery, therapy, and three dimensional displays. The critical aspects of such emerging nanoparticles with regards to meeting the ever-changing needs of future development are also discussed.

G-C3N4 Coated Upconversion Nanoparticles for 808 nm Near-Infrared Light Triggered Phototherapy and Multiple Imaging

Exploring novel photosensitizer (PS) with good stability and high light converting efficiency and designing novel structure to integrate deep penetrating near-infrared (NIR) light excitable up-conversion nanoparticles (UCNPs) and PS into one system are highly fascinating in the photodynamic therapy (PDT) field. In this study, a novel core–shell structured platform (UCNPs@g-C3N4–PEG) with all-in-one “smart” functions for simultaneous photodynamic therapy, photothermal therapy (PTT), and trimodal imaging properties has been rationally designed and fabricated. This system is composed of a core–shell–shell structured NaGdF4:Yb/Tm@NaGdF4:Yb@NaNdF4:Yb up-conversion luminescence (UCL) core and photoactive graphitic-phase carbon nitride (g-C3N4) mesoporous shell closely coated on individual core. This designed structure allows large specific surface area, high loading amount, close proximity to the UCL core, and almost no leakage of g-C3N4 PS, thus ensuring sufficient reactive oxygen species (ROS) to damage tumor...

Facile and high spatial resolution ratio-metric luminescence thermal mapping in microfluidics by near infrared excited upconversion nanoparticles

A local area temperature monitor is important for precise control of chemical and biological processes in microfluidics. In this work, we developed a facile method to realize micron spatial resolution of temperature mapping in a microfluidic channel quickly and cost effectively. Based on the temperature dependent fluorescence emission of NaYF4:Yb3+, Er3+ upconversion nanoparticles (UCNPs) under near-infrared irradiation, ratio-metric imaging of UCNPs doped polydimethylsiloxane can map detailed temperature distribution in the channel. Unlike some reported strategies that utilize temperature sensitive organic dye (such as Rhodamine) to achieve thermal sensing, our method is highly chemically inert and physically stable without any performance degradation in long term operation. Moreover, this method can be easily scaled up or down, since the spatial and temperature resolution is determined by an optical imaging system. Our method supplied a simple and efficient solution for temperature mapping on a heterogeneous surface where usage of an infrared thermal camera was limited.

Optimization of upconversion luminescence of Nd(3+)-sensitized BaGdF5-based nanostructures and their application in dual-modality imaging and drug delivery.

808 nm excited upconversion nanoparticles (UCNPs) have received extensive attention in the biomedical areas. However, one of the limitations of UCNPs is their lower luminescence efficiency. Aimed at this problem, a series of BaGdF5-based UCNPs were prepared by a layer-by-layer procedure. And UC luminescence properties are optimized by varying the doping concentration of rare earth ions, amount and types of shells. It is found that if the amount of core BaGdF5:20%Yb(3+)/2%Er(3+) was fixed at 0.5 mmol, the optimized conditions of three shell layers are 0.3 mmol of BaGdF5:10%Yb(3+), 0.5 mmol of BaNdF5 and 0.5 mmol of BaGdF5. Thus the UC luminescence intensity of the resultant nanoparticles BaGdF5:20%Yb(3+)/2%Er(3+)@BaGdF5:10%Yb(3+)@BaNdF5@BaGdF5 (Er@Yb@Nd@Gd) is enhanced more than four times compared with that of BaGdF5:20%Yb(3+)/2%Er(3+)@BaGdF5:10%Yb(3+)@BaNdF5 (Er@Yb@Nd). To further improve the biocompatibility and applications in the biological field, carboxymethyl chitosan (CMC), a type of biocompatible water-transfer agent, was used as a capping ligand to modify the surface of Er@Yb@Nd@Gd. An antitumor drug doxorubicin (DOX) was loaded to the CMC-modified Er@Yb@Nd@Gd nanocarriers by electrostatic interactions. The DOX can be selectively released in an acidic environment, which shows a pH-triggered drug release behavior. On the other hand, Er@Yb@Nd@Gd nanoparticles have excellent magnetic properties due to the presence of Gd components. T1-weighted magnetic resonance imaging (MRI) reveals the concentration-dependent brightening effect with longitudinal relaxivity (r1) as high as 43.77 s(-1) (mM)(-1), much higher than that of previous Gd(3+)-based counterparts. The results indicate that this multifunctional drug delivery system is expected to be a promising platform for simultaneous cancer therapy and bioimaging.

Titania coated upconversion nanoparticles for near-infrared light triggered photodynamic therapy.

Because of the limited penetration depth of visible light that generally excites most of the available photosensitizers (PSs), conventional photodynamic therapy (PDT) is limited to the treatment of superficial and flat lesions. Recently, the application of deep penetrating near-infrared (NIR) light excitable upconversion nanoparticles (UCNs) in conjunction with PDT has shown to have clear potential in the treatment of solid tumors due to its ability to penetrate thick tissue. However, various constructs developed so far have certain limitations such as poor or unstable PS loading, reducing their therapeutic efficacy and limiting their application to solution or cell-based studies. In this work, we present a method to fabricate uniform core-shell structured nanoconstruct with a thin layer of photocatalyst or PS-titanium dioxide (TiO2) stably coated on individual UCN core. Our design allows controllable and highly reproducible PS loading, preventing any leakage of PS compared to previously developed nanoconstructs, thus ensuring repeatable PDT results. Further surface modification of the developed nanoconstructs with polyethylene glycol (PEG) rendered them biocompatible, demonstrating good therapeutic efficacy both in vitro and in vivo.

Upconversion Fluorescence-SERS Dual-Mode Tags for Cellular and in Vivo Imaging

Fluorescent-surface enhanced Raman scattering (F-SERS) dual mode tags showed great potential for bioimaging due to the combined advantages of intuitive, fast imaging of fluorescence and multiplex capability of SERS technique. In previously reported F-SERS tags, organic fluorescent dyes or quantum dots were generally selected to generate fluorescence signal. Herein, we reported the first proof-of-concept upconversion fluorescence (UCF)-SERS dual mode tags based on near infrared (NIR) laser (980 nm) excited upconversion nanoparticles (UCNPs) for live-cell and in vivo imaging. Three components involved in this tag: NaYF4:Yb,Er UCNPs@SiO2 serving as the fluorescent core of the tag; silver nanoparticles in situ grown on the surface of UCNPs@SiO2 for generating characteristic Raman signal; and denatured BSA coating rendering the tag's stability and biocompatibility. The UCF-SERS tags integrated the NIR imaging capability of both fluorescent UCNPs and plasmonic SERS nanoprobe, which facilitated dual mode bioimaging investigation, especially for living animals. Ex vivo experiments revealed that with 980 nm and 785 nm NIR laser irradiations, the UCF and SERS signals of the tags could be detected from 3 and 7 mm deep pork tissues, respectively. Furthermore, the in vivo imaging capabilities of UCF-SERS tags were successfully demonstrated on living mice. The developed dual modality tags held great potential for medical diagnostics and therapy.

Engineering the Upconversion Nanoparticle Excitation Wavelength: Cascade Sensitization of Tri‐doped Upconversion Colloidal Nanoparticles at 800 nm

Cascade-sensitized 800 nm excited tri-doped upconversion nanoparticles (UCNPs) are developed for the first time. This novel class of UCNPs employ Nd3+ as an 800 nm photon sensitizer and Yb3+ as a bridging ion, and show strong upconversion emission without photobleaching. They outperform classical 980 nm excited UCNPs in regard to significantly decreased NIR photon absorption in water and decreased laser-induced water heating effects.