Lanthanide-doped Upconversion Nanoparticles Research Articles

Pre-activated nanoparticles with persistent luminescence for deep tumor photodynamic therapy in gallbladder cancer

Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

Plasmon modulated luminescent modes of upconversion nanoparticle by coupling with AuNR@SiO2 nanostructure

Lanthanide-doped upconversion nanoparticles (UCNPs) can convert near-infrared light into visible light emission, and have attracted more and more interests due to their great potential in ultrasensitive biosensors. However, it is still a huge challenge to manipulate the intensity ratio between different emission lines and realize the modulated up-conversion. In this work, the upconversion luminescence performance of UCNPs was regulated by coupling with Au nanorod-silicon core–shell (AuNR@SiO2) nanostructures. By changing the thickness and surface charge of the silica shell, the influence of the thickness and surface charge on the energy transfer of the UCNPs was explored. It is expected that the up-conversion luminescence effect of this composite nanostructure regulated by plasmons can provide a basis for the extensive exploration of biological detection and sensing applications.

Tm3+-doped upconversion nanoparticles water probing

Water probing based on lanthanide-doped upconversion nanoparticles (UCNPs) has aroused great interest due to the advantages of high photostability, short response time, no autofluorescence background, and low toxicity. Compared with widely used Er3+-doped UCNPs, Tm3+-doped UCNPs are not considered as efficient water probes due to the phonon energy mismatch. Here, we demonstrate the water probing based on Tm3+-doped UCNPs with excellent sensitivity and linearity, and reveal that the fractional photon-assisted Förster resonance energy transfer could play a significant role in the mechanism. The recorded sensitivities of up to 6.141%/vol% and 3.932%/vol% were achieved for the hydrogen oxide and deuterium oxide detection. Based on the developed UCNPs, we developed two sensing devices, namely, an UCNPs-coated micro-fiber and UCNPs-embedded silk, for distributed and wearable humidity sensing. Our study opens an unprecedented avenue to develop real-time, high-sensitivity, high-stability, biocompatible water probes serving the fields of cytobiology, pharmaceutics, environmental health and safety, fine chemical industry, and precision agriculture.

Self-assembled ratiometric sensor for specific detection of hypoxia in living cells based on lanthanide-doped upconversion nanoparticles and gold nanoparticles

We describes the development of a self-assembled nanoprobe for ratiometric sensing of hypoxia in living cells. The probe, UC-AuNPs, is composed of azo-functionalized upconversion nanoparticles (azo-UCNPs) and gold nanoparticles functionalized with β-cyclodextrin (CD-AuNPs). Under hypoxic conditions, reductases reduce azo derivatives on the UCNPs, leading to detachment of the CD-AuNPs and subsequent fluorescence recovery of the green emission. The ratiometric measurement incorporated into the strategy reduces the impact of external factors and improves sensitivity of the probe. The use of NIR excitation effectively minimizes interference from strong luminescence backgrounds in biosystems. The UC-AuNPs nanoprobe is able to effectively sense and monitor hypoxia conditions in living cells and has the potential to distinguish hypoxia-related diseases from healthy tissue, making it a valuable tool for early clinical diagnosis.

Enhanced upconversion of sub20 nm core/shell/shell nanophosphors for temperature and rhodamine B sensing

Lanthanide-doped upconversion (UC) nanoparticles (NPs) have attracted great attention in many emerging applications. Although multilayer structures have been employed to strengthen UC intensity, balancing the energy transfer (ET) efficiency from sensitizer to activator as well as the back energy transfer (BET) efficiency remains a critical issue. Herein, the ET processes in the BaYF5-based core/shell/shell NPs are comprehensively manipulated, resulting in greatly enhanced UC intensity. By using the sub20 nm BaYF5:2Yb2Er@BaYbF5@BaYF5 nanostructure, the efficiencies of incident light absorption and ET from the sensitizer in the interlayer to the activator in the core are improved, while the BET is limited. The UC intensity of this nanostructure was approximately 3.7 times that of normal BaYF5:20Yb2Er@BaYF5 NPs. The isolation of Yb and Er can remarkably restrict the negative thermal quenching (NTQ) effect, resulting in improved temperature sensing performance. Moreover, the BaYF5:2Yb2Er@BaYbF5@BaYF5 NPs can be used for selective sensing of rhodamine B. Our results highlight the comprehensive manipulation of ET processes in a core/shell/shell nanostructure to significantly improve the UC intensity.

Activating ultralow upconversion nanothermometry in neodymium sublattice for heart tissue imaging rapid-responsive

The fields of biosensitivity and biological imaging have received a lot of attention from rare earth-doped upconversion nanoparticles (UCNPs). However, owing to the relatively large energy difference of rare earth ions, biological sensitivity based on UCNPs is restricted to detect at low temperature. Here, we design core-shell-shell NaErF4:Yb@Nd2O3@SiO2 UCNPs as a dual-mode bioprobe that produces blue, green, and red multi-color upconversion emissions at extremely low temperatures between 100 K and 280 K. Based on the thermally coupled energy levels (TCELs) of Er3+ (2H11/2 and 4S3/2) and Nd3+ (4F5/2 and 4F3/2) at 100 K, the greatest relative sensitivity (SR) approaches 12.7% K−1. NaErF4:Yb@Nd2O3@SiO2 injection is used to achieve blue upconversion emission imaging of frozen heart tissue, showing that this UCNP can serve as a low-temperature sensitive biological fluorescence.

Biomimetic Upconversion Nanoplatform Synergizes Photodynamic Therapy and Enhanced Radiotherapy against Tumor Metastasis.

The easy recurrence and high metastasis of fatal tumors require the development of a combination therapy, which is able to overcome the drawbacks of monomodal strategies such as surgery, photodynamic therapy (PDT), and radiotherapy (RT). Taking the complementary advantages of PDT and RT, we present herein the integration of lanthanide-doped upconversion nanoparticles (UCNPs) with chlorin e6 (Ce6)-imbedded RBC membrane vesicles as a near-infrared-induced PDT agent for achieving synchronous depth PDT and RT with reduced radiation exposure. In such a nanoagent, gadolinium-doped UCNPs with strong X-ray attenuation ability act not only as a light transductor to activate the loaded photosensitizer Ce6 to allow PDT but also as a radiosensitizer to enhance RT. PDT with enhanced low-dose RT can achieve synergistic inhibition of tumor growth by producing reactive oxygen species to destroy local tumor cells and inducing strong T-cell-dependent immunogenic cell death to arrest systemic cancer metastasis. This combination of PDT and RT might be a potential appealing strategy for tumor eradication.

Extraordinary upconversion enhancement in mono-dispersed plasmonic resonant nanocavity coupling with lanthanide doped upconversion nanoparticles

In this work, we reported a monodispersed MDM (metal–dielectric-metal) type upconversion composite material with ultrahigh emission enhancement for the first time. Different from the planar configuration of traditional MDM systems, the proposed materials here consisting of silver nanoparticles as the metallic core, upconversion nanoparticles(UCNPs) as the intermediate dielectric layer, and silver layer as the metallic shell. The structural characteristics were investigated to explore the spectral band match between the plasmonics and UCNPs. The sandwich structure can create high density hot carriers at the nearfield region around the UCNPs, leading to the remarkable excitation enhancement. According to the proper structure design, the upconversion intensity can be enhanced by over five orders of magnitude. The outer metallic layer thickness, the diameter of attached UCNPs and the ambient refractive index were found responsible for the intensity enhancement. Such upconversion materials combined the merit of monodispersity and the high emission efficiency, which can improve their performance in bioimaging and photovoltaic device.

Quantitative Point of Care Tests for Timely Diagnosis of Early-Onset Preeclampsia with High Sensitivity and Specificity.

Preeclampsia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip-based lateral flow assay (LFA) using lanthanide-doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preeclampsia. We first measured circulating plasma FKBPL and CD44 protein concentrations from individuals with early-onset preeclampsia (EOPE), using ELISA. We confirmed that the CD44/FKBPL ratio is reduced in EOPE with a good diagnostic potential. Using our rapid LFA prototypes, we achieved an improved lower limit of detection: 10 pg ml-1 for FKBPL and 15 pg ml-1 for CD44, which is more than one order lower than the standard ELISA method. Using clinical samples, a cut-off value of 1.24 for CD44/FKBPL ratio provided positive predictive value of 100 % and the negative predictive value of 91 %. Our LFA shows promise as a rapid and highly sensitive point-of-care test for preeclampsia.

Luminescent Color Controller-Based Bilayer PC-UCNPs-PC Dynamically Modulate Photon Propagation

Lanthanide-doped upconversion nanoparticles (UCNPs) exhibit abundant emission wavelengths under near infrared (NIR) excitation. This property enables UCNPs to have potential for multicolor output. However, the realization of multicolor-tunable emission output in UCNPs at a fixed composition has remained challenging. Here, a luminescent color controller that can dynamically control the upconversion luminescence (UCL) colors from UCNPs is reported. By constructing bilayer photonic crystals (PCs) in which the UCNPs are distributed between the two-layer PCs, the propagation of green and red emission can be modulated by the top and bottom PCs, respectively. Moreover, the photonic bandgap (PBG) could be varied by changing the reflected angles, according to Bragg diffraction. Thus, the variation in the viewing angles also results in the yellow to blue and red to cyan structural color changes on the top and bottom bilayer PC-UCNPs-PC films. Correspondingly, the emission color outputs are changed from red to yellow-green and green to yellow-green, respectively. These findings provide a general method to achieve multicolor-tunable UCL by a bilayer PC-UCNPs-PC film. Moreover, the UCNPs with multicolor emissions in this work enrich the upconversion system and should have potential applications in display and anticounterfeiting.

UV Emission from Lanthanide-Doped Upconversion Nanoparticles in Super-Resolution Microscopy: Potential for Cellular Damage

Upconversion nanoparticles (UCNPs) co-doped with lanthanide ions have recently attracted significant attention as fluorescent probes for super-resolution microscopy (SRM). This is due to the advantages of UCNPs over other fluorescence probes, such as fluorescent proteins, owing to their unique optical properties, limited photobleaching, and sharp emissions. However, the concurrent emission of ultraviolet (UV) wavelength radiation by UCNPs and the potential for cell photodamage, which may limit useful live-cell analysis, have been overlooked. Here, UCNPs synthesized with eight commonly used combinations of Yb/Tm and Yb/Tm/Gd dopants were excited by either pulsed- or continuous-wave (CW) lasers to evaluate their UV emission. The ratio of emitted UV-A and UV-B was measured relative to blue emission at 475 nm, which is traditionally used for imaging during SRM. We demonstrate that most UCNP samples emit UV light and that the dopant concentration has a key role in generating UV emissions. In addition, the use of pulsed or CW lasers for excitation can lead to a large variation in the amount of UV emitted. This work highlights the importance of considering upconversion dopant composition and concentration, as well as analyzing the emission of synthesized UCNPs before their use to prevent unwanted cell photodamage during live-cell imaging by SRM. Moreover, it established a need to improve the visible light emission of UCNPs with respect to UV emission for SRM applications.

Plasmonic Photocatalysis Driven by Indirect Gold Excitation Via Upconversion Nanoparticle Emission Monitored In Situ by Surface-Enhanced Raman Spectroscopy

Lanthanide-doped upconversion nanoparticles (UCNPs) absorb low-energy photons, in the near-infrared region (NIR), and emit high-energy photons, in the visible or ultraviolet region (UV/Vis). The higher energy radiation emissions can be used to promote plasmonic photocatalytic reactions by coupling UCNPs with plasmonic nanoparticles. Thus, in this work, highly crystalline β-NaYF4:Yb3+,Er3+@NaYF4:Nd3+@NaYF4 UCNPs capped with an amino-modified nanosized silica shell were coupled with Au nanospheres (13 ± 2 nm). The plasmonic-driven dimerization of 4-aminothiophenol (4-ATP) to 4,4′-dimercaptoazobenzene (DMAB) was carried out solely by using the UCNP visible emissions to excite the Au nanoparticle localized surface plasmon resonance band. The reaction was monitored in situ through surface-enhanced Raman spectroscopy (SERS) and optimal conditions were achieved in order to eliminate secondary influences during spectra acquisition. The SERS substrates containing either UCNPs@SiO2-NH2/Au or SiO2-NH2/Au nanoparticles were prepared by the drop-cast method in silicon substrates. In the studied reaction conditions, plasmonic photocatalytic activity was observed only in the substrates containing UCNPs and Au nanoparticles. The plasmonic-driven reaction was achieved by UCNPs excitation with a 980 nm laser (25.7 mW), aligned in a Raman spectrometer, only after 5 s of exposition. Interactive document mapping (IDMAP), which is an unsupervised pattern recognition method, was applied to analyze the numerous SERS spectra acquired during the plasmonic photocatalytic measurements. The high values found for the silhouette coefficient (0.88 for the Si_SiO2-NH2/Au and 0.76 for the Si_NYF@SiO2-NH/Au substrate) indicate that strong discrimination among the Raman spectra was achieved. Thus, through IDMAP, it was observed that the SERS spectra obtained for the substrates containing either UCNPs@SiO2-NH2/Au or SiO2-NH2/Au corresponded to spectral features, respectively, from the DMAB product and the 4-ATP reagent, evidencing that, in the optimized reaction conditions, the dimerization occurred only through the interaction of the UCNPs with the Au nanospheres.

Frequency-Domain Method for Characterization of Upconversion Luminescence Kinetics.

The frequency-domain (FD) method provides an alternative to the commonly used time-domain (TD) approach in characterizing the luminescence kinetics of luminophores, with its own strengths, e.g., the capability to decouple multiple lifetime components with higher reliability and accuracy. While extensively explored for characterizing luminophores with down-shifted emission, this method has not been investigated for studying nonlinear luminescent materials such as lanthanide-doped upconversion nanoparticles (UCNPs), featuring more complicated kinetics. In this work, employing a simplified rate-equation model representing a standard two-photon energy-transfer upconversion process, we thoroughly analyzed the response of the luminescence of UCNPs in the FD method. We found that the FD method can potentially obtain from a single experiment the effective decay rates of three critical energy states of the sensitizer/activator ions involved in the upconversion process. The validity of the FD method is demonstrated by experimental data, agreeing reasonably well with the results obtained by TD methods.

In Situ Transformable Nanoplatforms with Supramolecular Cross-Linking Triggered Complementary Function for Enhanced Cancer Photodynamic Therapy.

In vivo cross-linking of nanoparticles is widely used to increase accumulation of therapeutic agents at tumor site for enhanced therapy. However, the components in nanoplatforms usually only play for one role and are independent of each other, unable to amplify their biofunctions. Herein, a complementary functioning tumor microenvironment triggered, supramolecular coordination-induced nanoparticle cross-linking strategy is constructed for enhanced photodynamic therapy. Manganese oxide (MnOx ) and polyhydroxy photosensitizer hypericin (Hyp) are coated and loaded onto lanthanide-doped upconversion nanoparticles (UCNPs) to form transformable UCNP@MnOx -Hyp. In CT26mouse colon cancer cells and xenograft tumors, UCNP@MnOx -Hyp is reduced by glutathione and H2 O2 , releasing Mn2+ and Hyp for in situ cross-linking to transform to UCNP@Mn2+ -Hyp. Compared to the simple photosensitizer-loaded UCNP@PEI-Hyp, the Mn2+ -Hyp coordination redshifts absorbance of Hyp and improves the energy transfer efficiency from UCNPs to Hyp (5.6-fold). In turn, the supramolecular coordination-induced UCNPs cross-linking exhibits enhanced luminescence recovery and increased intracellular accumulation of both UCNPs and Hyp, thus enhancing the photodynamic therapy efficacy both at cellular level (2.1-fold) and in vivo, realizing the function amplification of each component after responsive transformation and offering a new avenue for enhanced cancer therapy.

NIR light-driven photocatalytic NAD(P)H oxidation and H2O2 generation in situ for enhanced chemodynamic therapy and immune response

Chemodynamic therapy (CDT) is an appealing cancer treatment that converts endogenous H2O2 into highly toxic hydroxyl radicals to kill cancer cells. However, the limited amount of H2O2 in tumor cells constrains the application of CDT. Therefore, the strategy that can increase H2O2 level in situ could broaden its clinical application. Herein, we synthesized a supramolecule [Ru(bpy)2(Nabpy)](PF6)2 (Ru1) which can efficiently photo-catalyze NAD(P)H oxidation with simultaneous generation of H2O2 with a high yield at 76.4 %. The Ru1 and Fe2+ were then loaded on the mesoporous silica-encapsulated rare earth-doped upconversion nanoparticles (UCSRF), the intracellular H2O2 level can be elevated by 2.8 times upon the irradiation of near-infrared (NIR) light irradiation. Then, the intracellular H2O2 was transformed into hydroxyl radicals through Fenton reaction to achieve efficient CDT both in vitro and in vivo. Furthermore, we demonstrated that UCSRF could effectively enhance immunogenic cell death (ICD) effect, resulting in the reprogramming of the immunosuppressive tumor microenvironment to stimulate immune response. This work represents the first proof-of-concept study on photo-catalytically enhancing H2O2 production in situ upon NIR irradiation for spatiotemporal CDT.

Orthogonal Trichromatic Upconversion with High Color Purity in Core‐Shell Nanoparticles for a Full‐Color Display

AbstractMaterials with tunable emission colors has attracted increasing interest in both fundamental research and applications. As a key member of light‐emitting materials family, lanthanide doped upconversion nanoparticles (UCNPs) have been intensively demonstrated to emit light in any color upon near‐infrared excitation. However, realizing the trichromatic emission in UCNPs with a fixed composition remains a great challenge. Here, without excitation pulsed modulation and three different near‐infrared pumping, we report an experimental design to fine‐control emission in the full color gamut from core–shell‐structured UCNPs by manipulating the energy migration through dual‐channel pump scheme. We also demonstrate their potential application in full‐color display. These findings may benefit the future development of convenient and versatile optical methos for multicolor tuning and open up the possibility of constructing full‐color volumetric display systems with high spatiotemporal resolution.

Orthogonal Trichromatic Upconversion with High Color Purity in Core-Shell Nanoparticles for a Full-Color Display.

Materials with tunable emission colors has attracted increasing interest in both fundamental research and applications. As a key member of light-emitting materials family, lanthanide doped upconversion nanoparticles (UCNPs) have been intensively demonstrated to emit light in any color upon near-infrared excitation. However, realizing the trichromatic emission in UCNPs with a fixed composition remains a great challenge. Here, without excitation pulsed modulation and three different near-infrared pumping, we report an experimental design to fine-control emission in the full color gamut from core-shell-structured UCNPs by manipulating the energy migration through dual-channel pump scheme. We also demonstrate their potential application in full-color display. These findings may benefit the future development of convenient and versatile optical methos for multicolor tuning and open up the possibility of constructing full-color volumetric display systems with high spatiotemporal resolution.

Recent advances in lanthanide-doped up-conversion probes for theranostics.

Up-conversion (or anti-Stokes) luminescence refers to the phenomenon whereby materials emit high energy, short-wavelength light upon excitation at longer wavelengths. Lanthanide-doped up-conversion nanoparticles (Ln-UCNPs) are widely used in biomedicine due to their excellent physical and chemical properties such as high penetration depth, low damage threshold and light conversion ability. Here, the latest developments in the synthesis and application of Ln-UCNPs are reviewed. First, methods used to synthesize Ln-UCNPs are introduced, and four strategies for enhancing up-conversion luminescence are analyzed, followed by an overview of the applications in phototherapy, bioimaging and biosensing. Finally, the challenges and future prospects of Ln-UCNPs are summarized.

DUCNP@Mn-MOF/FOE as a Highly Selective and Bioavailable Drug Delivery System for Synergistic Combination Cancer Therapy.

Heterostructures comprising lanthanide-doped upconversion nanoparticles (DUCNPs) and metal-organic frameworks (MOFs) are emerging as promising nanosystems for integrating medical diagnosis and treatment. Here, the DUCNP@Mn-MOF nanocarrier was developed, which showed good efficiency for loading and delivering a cytotoxic antitumor agent (3-F-10-OH-evodiamine, FOE). The combined advantages of the pH-responsive and peroxidase-like properties of Mn-MOF and the unique optical features of DUCNPs granted the DUCNP@Mn-MOF/FOE system synergistic chemodynamic and chemotherapeutic effects. The DUCNP@Mn-MOF nanocarrier effectively overcame the intrinsic limitations of FOE, such as its unfavorable physicochemical properties and limited in vivo potency. This complexed nanosystem was responsive to the tumor microenvironment and showed excellent tumor targeting capability. Thus, DUCNP@Mn-MOF/FOE exhibited highly selective and bioavailable drug delivery properties and is promising for cancer therapy. In a mouse breast cancer model, DUCNP@Mn-MOF/FOE inhibited tumor growth without significant toxicity. Therefore, the proposed nanosystem represents a promising theragnostic platform for multimodal combination diagnosis and therapy of tumors.

Dual Band-Edge Enhancing Overall Performance of Upconverted Near-Infrared Circularly Polarized Luminescence for Anticounterfeiting

Circularly polarized luminescence (CPL) is one of the critical chiroptical properties for chiral nanomaterials, which exhibit wide potential applications in many research fields. However, it remains a big challenge for real application, limited by their small luminescence dissymmetry factor or low emission intensity. Here, an upconverted near-infrared circularly polarized luminescence (UC-NIR-CPL) system is constructed based on the chiroptical property of chiral liquid crystals, embedding with the lanthanide-doped upconversion nanoparticles. More importantly, a strategy for improving the overall performance of UC-NIR-CPL was proposed and realized by taking advantage of the "dual-band-edge enhancement effect", wherein the glum value was amplified, while the NIR emission intensity showed dual enhancement and the threshold of excitation was decreased. Based on the improved overall performance of the UC-NIR-CPL, which can be used as a distinctive covert light, a kind of photonic barcode with multiple encryptions was realized. These findings will upgrade the level of information encryption through improving the overall performance of CPL-active materials.