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Focused on the newly secreted tumorous exosomes during melanoma immunotherapy, this work has pioneered an ultra-sensitive spatiotemporal-specific exosome detection strategy, leveraging advanced exosomal membrane engineering techniques. The proposed strategy harnesses the power of amplified lanthanide luminescence signals on these exosomes, enabling precise and real-time monitoring of the efficacy of melanoma immunotherapy. The methodology comprises two pivotal steps. Initially, Ac4ManNAz-associated metabolic labeling is employed to evolve azide groups onto the membranes of newly secreted exosomes with remarkable selectivity. These azide groups serve as versatile clickable artificial tags, enabling the precise identification of melanoma exosomes emerging during immunotherapy. Subsequently, lanthanide-nanoparticle-functionalized polymer chains are controllably grafted onto the exosome surfaces through click chemistry and in situ Fenton-RAFT polymerization, serving as robust signal amplifiers. When integrated with time-resolved fluorescence detection, this strategy yields detection signals with an exceptionally high signal-to-noise ratio, enabling ultra-sensitive detection of PD-L1 antigen expression levels on the spatiotemporal-specific exosomes. The detection strategy boasts a wide linear concentration range spanning from 1.7 × 104 to 1.7 × 109 particles/mL, with a remarkable theoretical detection limit of 1.28 × 103 particles/mL. The remarkable enhancements in detection sensitivity and accuracy facilitate the evaluation of the efficacy of immunotherapeutic interventions in the mouse B16 melanoma model, notably revealing a substantial disparity in PD-L1 levels between immunotherapy-treated and untreated groups (P < 0.01) and further emphasizing the cumulative therapeutic effect that intensifies with repeated treatments (P < 0.001).

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Rapid and quantitative detection of isoquercitrin (Isq) has been attracting much attention due to its outstanding pharmacological and physiological activities. Herein, an interesting 48-metal Zn(II)-Nd(III) nanocluster (1, molecular sizes 1.3 × 2.8 × 3.1 nm) with salen-type Schiff base ligand was constructed as molecular sensor for the luminescence detection of Isq. 1 exhibits visible ligand-centered emission and NIR luminescence of Nd(III), and shows ratiometric fluorescence response to Isq with high sensitivity even in the presence of other interferences. The fluorescence sensing behavior can be expressed by a second-order equation I1060nm/I480nm = A*[Isq]2 + B*[Isq] + C, which is used to quantitatively analyze the Isq concentrations in DMF and FCS. The LODs to Isq for the ligand-centered and lanthanide emissions of 1 in DMF are 0.21 µM and 0.11 nM, respectively. The quenching of the ligand-centered emission of 1 caused by Isq is attributed to the competitive absorption of light energy and "inner effect", while, the luminescence enhancement is due to the "antenna effect".

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A lanthanide complex based on europium (Eu) and chelidamic acid was synthesized (Eu-CHE) and characterized. The complex Eu-CHE exhibited intense luminescence at 615 nm under excitation at 300 nm and was further investigated for highly sensitive turn-off detection of l-kynurenine (l-kyn), a cancer biomarker. The probe detected l-kyn linearly from 6 nM to 0.2 µM with a limit of detection and limit of quantification of 1.37 and 4.57 nM, respectively. The probe was investigated for selectivity towards l-kyn among co-existing amino acids and further extended for detecting l-kyn from human serum and urine samples. A low-cost paper strip-based sensing platform was also developed for the visual detection of l-kyn.

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Lanthanide luminescent hydrogels have broad application prospects in various fields. However, most of lanthanide hydrogels possess relatively simple functions, which is not conducive to practical applications. Therefore, it is becoming increasingly urgent to develop multifunctional hydrogels. Herein, a multifunctional chitosan-based lanthanide luminescent hydrogel with ultra-stretchability, multi-adhesion, excellent self-healing, emission color tunability, and good antibacterial ability was prepared by a simple one-step free radical polymerization. In this work, our designed lanthanide complexes [Ln(4-VDPA)3] contain three reaction sites, which can be copolymerized with N-[tris(hydroxymethyl) methyl] acrylamide (THMA), acrylamide (AM), and diacryloyl poly(ethylene glycol) (DPEG) to form the first chemical crosslinking network, while hydroxypropyltrimethyl ammonium chloride chitosan (HACC) interacts with the hydroxyl and amino groups derived from the chemical crosslinking network through hydrogen bonds to form the second physical crosslinking network. The structure of the double network as well as the dynamic hydrogen bond and lanthanide coordination endow the hydrogel with excellent stretchability, adhesion and self-healing properties. Moreover, the introduction of lanthanide complexes and chitosan makes the hydrogel exhibit outstanding luminescence and antibacterial performances. This research not only realizes the simple synthesis of multifunctional luminescent hydrogels, but also provides a new idea for the fabrication of biomass-based hydrogels as intelligent and sustainable materials.

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Here, we demonstrate a label-free dual optical response strategy for the detection of cytochrome c (Cyt c) with ultrahigh sensitivity using highly luminescent lanthanides containing inorganic-organic hybrid nanotubular sensor arrays. These sensor arrays are formed by the sequential incorporation of the photosensitizers 2,3-dihydroxynaphthalene (DHN) or 1,10-phenanthroline (Phen), and trivalent lanthanide terbium ions (Tb3+) into sodium lithocholate (NaLC) nanotube templates. Our sensing platform relies on the detection and quantification of Cyt c in solution by providing dual photoluminescence quenching responses from the nanotubular hybrid arrays in the presence of Cyt c. The large quenching of the sensitized Tb3+ emission within the DHN/Phen-Tb3+-NaLC nanotubular sensor arrays caused by the strong binding of the photosensitizers to Cyt c provides an important signal response for the selective detection of Cyt c. This long-lived lanthanide emission response-based sensing strategy can be highly advantageous for the detection of Cyt c in a cellular environment eliminating background fluorescence and scattering signals through time-gated measurements. The DHN containing nanotubular sensor arrays (DHN-NaLC and DHN-Tb3+-NaLC) provide an additional quenching response characterized by a unique spectral valley splitting with quantized quenching dip on the DHN fluorescence emission. This spectral quenching dip resulting from efficient FRET between the protein bound DHN photosensitizer and the heme group of Cyt c serves as an important means for specific detection and quantification of Cyt c in the concentration range of 0-30 µM with a low detection limit of around 20 nM.

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The synthesis of a family of chiral and enantiomerically pure pyridyl-diamide (pda) ligands that upon complexation with europium [Eu(CF3SO3)3] result in chiral complexes with metal centered luminescence is reported; the sets of enantiomers giving rise to both circular dichroism (CD) and circularly polarized luminescence (CPL) signatures. The solid-state structures of these chiral metallosupramolecular systems are determined using X-ray diffraction showing that the ligand chirality is transferred from solution to the solid state. This optically favorable helical packing arrangement is confirmed by recording the CPL spectra from the crystalline assembly by using steady state and enantioselective differential chiral contrast (EDCC) CPL Laser Scanning Confocal Microscopy (CPL-LSCM) where the two enantiomers can be clearly distinguished.

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There is an unmet need for easy-to-visualize drug carriers that can deliver therapeutic cargoes deep into solid tumors. Herein, we report the preparation of ultrasmall luminescent imine-based lanthanide nanocages, Eu60 and Tb60 (collectively Ln60 ), designed to encapsulate anticancer chemotherapeutics for tumor therapy. The as-prepared nanocages possess large cavities suitable for the encapsulation of doxorubicin (DOX), yielding DOX@Ln60 nanocages with diameters around 5 nm. DOX@Ln60 are efficiently internalized by breast cancer cells, allowing the cells to be visualized via the intrinsic luminescent property of Ln(III). Once internalized, the acidic intracellular microenvironment promotes imine bond cleavage and the release of the loaded DOX. DOX@Ln60 inhibits DNA replication and triggers tumor cell apoptosis. In a murine triple negative breast cancer (TNBC) model, DOX@Ln60 was found to inhibit tumor growth with negligible side effects on normal tissues. It proved more effective than various controls, including DOX and Ln60 . The present nanocages thus point the way to the development of precise nanomedicines for tumor imaging and therapy.

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Developing smart materials capable of solid-state multicolor photoluminescence (PL) switching in response to multistimuli is highly desirable for advanced anticounterfeiting. Here, a ternary MOF hybrid showing hydro-photo-thermo-responsive multicolor PL switching in the solid state is presented. This hybrid is constructed by co-immobilizing Eu3+ and methyl viologen (MV) cations within an anionic MOF via the cation-exchange approach. The confined guest cations are well arranged in the framework channels, facilitating the synergistic realization of stimuli-responsive multiple PL color-switching through intermolecular coupling. The hybrid undergoes a rapid and reversible PL color-switching from red to blue upon water simulation, which is achieved by activating the blue emission of the framework linker while simultaneously quenching the Eu3+ emission. Furthermore, the hybrid displays photo-thermo-responsive PL switching from red to dark. UV-light irradiation or heating triggers the chromic conversion of MV to its colored radical form, which exhibits perfect spectral overlap with Eu3+ , thus activating Förster resonance energy transfer (FRET) from Eu3+ to MV radicals and quenching the Eu3+ emission. Inspired by these results, PL morse patterns are designed and fabricated using a novel triple-level encryption strategy, showcasing the exciting potential of this hybrid in advanced anticounterfeiting applications.

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Ischemic stroke (IS) is one of the most dangerous medical conditions resulting in high mortality and morbidity. The increased brain temperature after IS is closely related to prognosis, making it highly significant for the early diagnosis and the progression evaluation of IS. Herein, a temperature-responsive near infrared (NIR) emissive lanthanide luminescence nanoparticle is developed for the early diagnosis and brain temperature detection of IS. After intravenous injection, the nanoparticles can pass through the damaged blood-brain barrier of the ischemic region, allowing the extravasation and enrichment of nanoparticles into the ischemic brain tissue. The NIR luminescence signals of the nanoparticles are used not only to judge the location and severity of the cerebral ischemic injury but also to report the brain temperature variation in the ischemic area through a visualized way. The results show that the designed nanoparticles can be used for the early diagnosis of ischemic stroke and minimally invasive temperature detection of cerebral ischemic tissues in transient middle cerebral artery occlusion mice model, which is expected to make the clinical diagnosis of ischemic stroke more rapid and convenient, more accurately evaluate the state of brain injury in stroke patients and also guide stroke hypothermia treatment.

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The brightness of doped luminescent materials is usually limited by the ubiquitous concentration quenching phenomenon resulting in an intractable tradeoff between internal quantum efficiency and excitation efficiency. Here, an intrinsic suppression of concentration quenching in sensitized luminescent systems, by exploiting the competitive relationship between light emitters and quenchers in trapping excitation energies from sensitizers, is reported. Although Cr3+ sensitizers and trivalent lanthanide (Ln3+ , Ln = Yb, Nd, and Er) emitters themselves are highly susceptible to concentration quenching, the unprecedentedly high-brightness luminescence of Cr3+ -Ln3+ systems is demonstrated in the short-wave infrared (SWIR) range employing high concentrations of Cr3+ , whereby a record photoelectric efficiency of 23% is achieved for SWIR phosphor-converted light-emitting diodes, which is about twice as high as those previously reported. The results underscore the beneficial role of emitters in terminating excitation energies, opening up a new dimension for developing efficient sensitized luminescent materials.

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Macrocyclic confinement-induced supramolecular luminescence materials have important application value in the fields of bio-sensing, cell imaging, and information anti-counterfeiting. Herein, a tunable multicolor lanthanide supramolecular assembly with white light emission is reported, which is constructed by co-assembly of cucurbit[7]uril (CB[7]) encapsulating naphthylimidazolium dicarboxylic acid (G1 )/Ln (Eu3+ /Tb3+ ) complex and carbon quantum dots (CD). Benefiting from the macrocyclic confinement effect of CB[7], the supramolecular assembly not only extends the fluorescence intensity of the lanthanide complex G1 /Tb3+ by 36 times, but also increases the quantum yield by 28 times and the fluorescence lifetime by 12 times. Furthermore, the CB[7]/G1 /Ln assembly can further co-assemble with CD and diarylethene derivatives (DAE) to realize the intelligently-regulated full-color spectrum including white light, which results from the competitive encapsulation of adamantylamine and CB[7], the change of pH, and photochromic DAE. The multi-level logic gate based on lanthanide supramolecular assembly is successfully applied in anti-counterfeiting system and information storage, providing an effective method for the research of new luminescent intelligent materials.

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Metallo-supramolecular polymers offer a highly controllable platform for sensing. Their modular characteristics obtained by the ability of varying both building blocks, the metal ion and the organic ligand, provide tunability of their optical and chemical properties. Specifically, polymers based on lanthanide ions and conjugated aromatic ligands exhibit enhanced luminescence properties that can be altered by external stimulation. Herein, using europium-based polymers, we demonstrate the ability to detect different pharmaceutical amines, including in complex biological media, based on their luminescence quenching efficiency as a result of their polymer dissociation capacity. A combination of absorption, luminescence, and NMR measurements reveals combined static and dynamic quenching mechanisms that enable selective sensing of strong basic amines with high pKa values.

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The photophysics of a europium(III) complex of 1,4,7,10-tetraazacycododecane-1,4,7-triacetic acid-10-(2-methylene)-1-azathioxanthone was investigated in three buffer systems and at three pH values. The buffers-phosphate buffered saline (PBS), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), and universal buffer (UB)-had no effect on the europium luminescence, but a lower overall emission intensity was determined in HEPES. It was found that this was due to quenching of the 1-azathioxanthone first excited singlet state by HEPES. The effect of pH on the photophysics of the complex was found to be minimal, and protonation of the pyridine nitrogen was found to be irrelevant. Even so, pH was shown to change the intensity ratio between 1-azathioxanthone fluorescence and europium luminescence. It was concluded that the full photophysics of a potential molecular probe should be investigated to achieve the best possible results in any application.

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Undoubtably, it is challenging to simultaneously determine the identity, enantiomeric excess (ee), and total concentration of an enantiomer by just one optical measurement. Herein, we design a chiral tetrahedron Eu4(LR)4 with circularly polarized luminescence (CPL), which presents highly selective/stereoselective, rapid, and "turn-on" CPL response to chiral diamines, rather than the monoamino compounds, such as monoamines or amino alcohols. By recording the left- and right-CPL intensities of the Eu3+ ion at 591 nm, the enantiomeric composition and concentration of chiral diamines can be simultaneously determined by monitoring the glum value and total emission intensity (IL + IR), respectively. Spectroscopy analyses demonstrate that the variations of glum depend on the inversion and maintenance of configuration around the Eu3+ ion (Δ â†” Λ), while the "turn-on" response arises from the raising of the T1 state of the ligand. The molecule/electron structural variations are proposed from the synergetic supramolecular interactions of NH2 groups with pendant diols and trifluoroacetyl groups.

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Luminescent aerogels based on sodium alginate cross-linked with ions of rare earth elements (Eu3+, Tb3+, Sm3+) and containing phenanthroline, thenoyltrifluoroacetone, dibenzoylmethane, and acetylacetone as ligands introduced into the matrix during the impregnation of alginate aerogels (AEG), were obtained for the first time in a supercritical carbon dioxide medium. The impregnation method used made it possible to introduce organically soluble sensitizing ligands into polysaccharide matrices over the entire thickness of the sample while maintaining the porous structure of the aerogel. It is shown that the pore size and their specific area are 150 nm and 270 m2/g, respectively. Moreover, metal ions with content of about 23 wt.%, acting as cross-linking agents, are uniformly distributed over the thickness of the sample. In addition, the effect of sensitizing ligands on the luminescence intensity of cross-linked aerogel matrices is considered. The interaction in the resulting metal/ligand systems is unique for each pair, which is confirmed by the detection of broad bands with individual positions in the luminescence excitation spectra of photoactive aerogels.

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Detecting luminescence beyond 750-800 nm becomes problematic as most conventional detectors are less sensitive in this range, and as simple corrections stops being accurate. Lanthanide luminescence occurs in narrow bands across the spectrum from 350-2000 nm. The most emissive lanthanide(III) ions have bands from 450 nm to 850 nm, some with additional bands in the NIR. Investigating NIR bands are hard, but the difficulties already start at 700 nm. In general, the photon flux from lanthanide(III) emitters is not great, and the bands beyond 700 nm are very weak, we therefore decided to build a spectrometer based on cameras for microscopy with single-photon detection capabilities. This was found to allieviate all limitations and to allow for fast and efficient recording of luminescence spectra in the range from 450 to 950 nm. The spectrometer characteristics were investigated and the performance was benchmarked against two commercial spectrometers. We conclude that this spectrometer is ideal for investigating lanthanide luminescence, and all other emitters with emission in the target range.

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EuIII and YbIII complexes with the carbazole-dipicolinato ligand dpaCbz2-, namely K3[Eu(dpaCbz)3] and K3[Yb(dpaCbz)3], were isolated. The EuIII complex displayed metal-centred emission upon one-photon excitation with a sensitized emission efficiency Φ L Ln of 1.8±0.3 %, corresponding to an intrinsic emission efficiency Φ Ln Ln of 46% and a sensitization efficiency of ηsens 3.9%, with an emission lifetime of the emissive state τ of 1.087±0.005 ms. The YbIII complex displayed Φ L Ln of 0.010±0.001 %, and a τ of 2.32±0.06 µs. The EuIII-centred emission was sensitized as well upon two-photon excitation and a two-photon absorption cross-section σ2PA of 63 GM at 750 nm was determined for the complex. The one- or two-photon sensitized emission intensity of the EuIII complex changes by more than two-fold when the solvent viscosity is varied in the range 0.5 - 200 cP and the emission is independent of dissolved oxygen. The YbIII complex displays a change in emission intensity as well. However, in this case, a dependence of the emission intensity on dissolved oxygen content was observed.

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Two lanthanide-containing porous coordination polymers, [Ln2(bpdc)6(phen)2]·nH2O (1) and [Ln2(bpdc)6(terpy)2]·3H2O (2) (Ln = Pr, Nd, or Sm-Dy; bpdc: 2,2'-bipyridine-5,5'-dicarboxylic acid; phen: 1,10-phenanthroline; and terpy: 2,2':6',2″-terpyridine), have been hydrothermally synthesized and structurally characterized by powder and single-crystal X-ray diffraction. Crystallographic analyses reveal that compounds 1 and 2 feature Ln3+-containing dimeric nodes that form a porous two-dimensional (2D) and nonporous three-dimensional (3D) framework, respectively. Each material is stable in aqueous media between pH 3 and 10 and exhibits modest thermal stability up to ∼400 °C. Notably, a portion of the phen and bpdc ligands in 1 can be removed thermally, without compromising the crystal structure, causing the surface area and pore volume to increase. The optical properties of 1 and 2 with Gd3+, Sm3+, Tb3+, and Eu3+ are explored in the solid state using absorbance, fluorescence, and lifetime spectroscopies. The analyses reveal a complex blend of metal and ligand emission in the materials containing Sm3+ and Tb3+, while those featuring Eu3+ are dominated by intense metal-based emission. Compound 1 with Eu3+ shows promise for the capture and detection of the uranyl cation (UO2)2+ from aqueous media. In short, uranyl capture is observed at pH 4, and the adsorption thereof is detectable via vibrational and fluorescence spectroscopies and colorimetrically as the off-white color of 1 turns yellow with uptake. Finally, both 1 and 2 with Eu3+ produce bright red emission upon irradiation with Cu Kα X-ray radiation (8.04 keV) and are candidate materials for applications in solid-state scintillation.

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Rapid and accurate detection of phosphate (Pi) in complex biological fluid is of critical importance for timely warning of Pi accumulation and monitoring Pi related pathological process. Up to date, various luminescent probes have been developed for Pi determination in aqueous media. However, the huge obstacles of the current probes suffer from the inherent issues such as time-consuming, tedious preparation and unavoidable background interference during Pi detection. To circumvent this limitation, we proposed a universal and facile strategy to fabricate a novel sensitizer-Ln3+@surfactant micelle probe with time-resolved luminescent (TRL) superiority through the self-assembly of sensitizer, Ln3+ and surfactant. Through this design, the sensitizer-Ln3+ chelate can be encapsulated into the surfactant constructed micelle and Ln3+ luminescence can be substantially lighted up through the effective energy transfer from the coordinated sensitizer and the assistance of Triton X-100. Such high TRL signal can be sensitively and specifically quenched by Pi, which was attributed to the specific coordination competition between sensitizer and Pi towards Ln3+. Benefitting from the background-free interference and highly sensitive TRL response of the sensitizer-Ln3+@surfactant probe, we achieved the rapid, selective and sensitive detection of Pi in the range of 0.5-120 µM with a limit of detection (LOD) of 0.19 µM. Furthermore, the accuracy of the proposed method based on the Ln3+ involved micelle probes was further verified through the quantitation of Pi in real biological samples.

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The recent discoveries of the first proteins that bind lanthanides as part of their biological function not only are relevant to the emerging field of lanthanide-dependent biology, but also hold promise to revolutionize the technologically critical rare earths industry. Although protocols to assess the thermodynamics of metal-protein interactions are well established for "traditional" metal ions in biology, the characterization of lanthanide-binding proteins presents a challenge to biochemists due to the lanthanides' Lewis acidity, propensity for hydrolysis, and high-affinity complexes with biological ligands. These properties necessitate the preparation of metal stock solutions with very low buffered "free" metal concentrations (e.g., femtomolar to nanomolar) for such determinations. Herein we describe several protocols to overcome these challenges. First, we present standardization methods for the preparation of chelator-buffered solutions of lanthanide ions with easily calculated free metal concentrations. We also describe how these solutions can be used in concert with analytical methods including UV-visible spectrophotometry, circular dichroism spectroscopy, Förster resonance energy transfer (FRET), and sensitized terbium luminescence, in order to accurately determine dissociation constants (Kds) of lanthanide-protein complexes. Finally, we highlight how application of these methods to lanthanide-binding proteins, such as lanmodulin, has yielded insights into selective recognition of lanthanides in biology. We anticipate that these protocols will facilitate discovery and characterization of additional native lanthanide-binding proteins, will motivate the understanding of their biological context, and will prompt their applications in biotechnology.

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