Currently, enzyme-responsive nanomaterials have shown great promise in prognosis or diagnosis of disease biomarker. However, the great obstacle for conventional enzyme-responsive nanomaterials frequently lies in autofluorescence interference, poor monodispersity, uncontrollable size and morphology, low optical stability, and biotoxicity, which fundamentally impede their practical application in biological systems. To overcome these deficiencies, we proposed a novel strategy for reliable and precise detection of an enzyme disease biomarker, alkaline phosphatase (ALP), through lanthanide (Ln³⁺) nucleotide nanoparticles (LNNPs) with extremely improved monodispersity and uniformity, which were achieved by the coordination self-assembly between ATP and Ln³⁺ inside micellar nanoreactor. Specifically, for ATP-Ce/Tb LNNPs, highly improved photoluminescence (PL) emission of Tb³⁺ can be achieved via efficient Ce³⁺ sensitization. We demonstrated that ALP could specifically cleave the phosphorus–oxygen (P–O) bonds of ATP and result in the collapse of ATP-Ce/Tb scaffold, finally leading to the PL quenching of Tb³⁺. By taking advantage of time-resolved (TR) PL technique, the fabricated ATP-Ce/Tb LNNPs presented superior selectivity and sensitivity for the ALP bioassay in complicated serum samples, thus revealing the great potential of ATP-Ce/Tb LNNPs in the areas of ALP-related disease prognosis and diagnosis.

Hybrid composites made of metal-organic frameworks (MOFs) and lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable interest for their synergistically enhanced functions in various applications such as chemical sensing, photocatalysis, anticounterfeiting and nanomedicine. However, precise assembly of MOF/UCNP hybrid composites with tunable morphologies remains a challenge due to the lack of effective synthetic methods and fundamental understanding of the growth mechanisms. Herein, we propose a modulator-directed assembly strategy to synthesize a series of ZIF-8@UCNP composites (ZIF-8 = zeolitic imidazolate framework-8). The UCNPs densely paved on the surface of ZIF-8 microcrystals and endowed the composites with intense upconversion blue emission, which were verified by steady-state/transient photoluminescence (PL) spectroscopy and single-particle imaging. Ethylenediamine (EDA) was firstly used as a modulator to fine-tune the predominant MOF facets and realized distinct morphologies of the composites. By adjusting the concentration of EDA from 0 to 25 mmol/L, the morphology of the ZIF-8@UCNP composites was tuned from rhombic dodecahedron (RD) to truncated rhombic dodecahedron (TRD), cube with truncated edges (CTE), cube, and finally a unique form of interpenetration twins (IT). The nucleation and growth process of the ZIF-8@UCNP composites was monitored by time-dependent scanning electron microscopy (SEM) images and the formation mechanism was thoroughly revealed. Furthermore, we demonstrated that the strategy for assembly of morphology-controllable ZIF-8@UCNP composites was generally applicable to various UCNPs with different sizes and shapes. The proposed strategy is expected to open up new avenues for the controllable synthesis of MOF/UCNP composites toward diverse applications.

Luminescent metal halides doped with ns²-metal ions such as 6s²-metal Bi³⁺ have aroused reviving interest owing to their outstanding optical properties; however, the origin of the photoluminescence (PL) remains controversial and unclear. Herein, we report a strategy for the controlled synthesis of Bi³⁺-doped vacancy-ordered double perovskite Cs₂SnCl₆ nanocrystals (NCs) and unravel the triplet excited-state dynamics of Bi³⁺ through temperature-dependent PL and ultrafast femtosecond transient absorption spectroscopies. Owing to the aliovalent Bi³⁺ doping in the spatially confined zero-dimensional (0D) structure of Cs₂SnCl₆, Bi³⁺ ions experience an enhancive Jahn-Teller distortion in the excited state, which results in intense broadband blue PL originating from the inter-configurational ³P_0,1 → ¹S₀ transitions of Bi³⁺ at 450 nm, with a large Stokes shift and a quantum yield of 35.2%. Specifically, an unusual thermal-enhanced Jahn-Teller splitting of the excitation band and a remarkable transition of the PL lifetime from ms at 10 K to μs at 300 K were observed, as solid evidence for the isolated Bi³⁺ emission. These findings clarify the controversy about the PL origin in ns²-metal ion-doped lead-free luminescent metal halides, thereby paving the way for exploring their optoelectronic applications.

Inorganic luminescent nanocrystals (NCs) doped with main-group ns²-metal ions have evoked tremendous interest in many technological fields owing to their superior optical properties. Herein, we report a new class of luminescent nanoprobes based on 5s²-metal Sb³⁺-doped CaS NCs that are excitable by using a near ultraviolet light-emitting diode. The optical properties and excited-state dynamics of Sb³⁺ in CaS NCs are comprehensively surveyed through temperature-dependent steady-state and transient photoluminescence (PL) spectroscopies. Owing to the strong electron–phonon coupling of Sb³⁺ in CaS NCs, Sb³⁺ ions experience a dynamic Jahn-Taller distortion on the excited state, which results in bright green PL of Sb³⁺ with a broad emission band, a large Stokes shift, and a high PL quantum yield up to 17.3%. By taking advantage of the intense PL of Sb³⁺, we show in proof-of-concept experiments the application of biotinylated CaS: Sb³⁺ NCs as sensitive luminescent nanoprobes for biotin receptor-targeted cancer cell imaging and zebrafish imaging with a high imaging contrast. These findings provide fundamental insights into the excited-state dynamics of Sb³⁺ in CaS NCs, thus laying a foundation for future design of novel and versatile luminescent nanoprobes via main-group ns²-metal doping.

Multiplexed intracellular detection is desirable in biomedical sciences for its higher efficiency and accuracy compared to the single-analyte detection. However, it is very challenging to construct nanoprobes that possess multiple fluorescent signals to recognize the different intracellular species synchronously. Herein, we proposed a novel dual-excitation/dual-emission upconversion strategy for multiplexed detection through the design of upconversion nanoparticles (UCNP) loaded with two dyes for sensitization and quenching of the upconversion luminescence (UCL), respectively. Based on the two independent energy transfer processes of near-infrared (NIR) dye IR845 to UCNP and UCNP to visible dye PAPS-Zn, ClO^- and Zn²⁺ were simultaneously detected with a limit of detection (LOD) of 41.4 and 10.5 nM, respectively. By utilizing a purpose-built 830/980 nm dual-laser confocal microscope, both intrinsic and exogenous ClO^- and Zn²⁺ in live MCF-7 cells have been accurately quantified. Such dual-excitation/dual-emission ratiometric UCL detection mode enables not only monitoring multiple intracellular analytes but also eliminating the detection deviation caused by inhomogeneous probe distribution in cells. Through modulation of NIR dye and visible dye with other reactive groups, the nanoprobes can be extended to analyze various intracellular species, which provides a promising tool to study the biological activities in live cells and diagnose diseases.

Lanthanide-based luminescent anti-counterfeiting materials are widely used in various kinds of products. However, the emission color of traditional lanthanide-based luminescent materials usually remains nearly unaltered upon different excitation lights, which may only work for single-level anti-counterfeiting. Herein, the NaYbF₄: 2%Er@NaYF₄ core/shell nanoplates (NPs) with "chameleon-like" optical behavior are developed. These NPs display single-band red or green downshifting (DS) emission upon excitation at 377 or 490 nm, respectively. Upon 980 nm excitation, the color of upconversion (UC) emission can be finely tuned from green to yellow, and to red with increasing the excitation power density from 0.1 to 4.0 W/cm². The proposed materials readily integrate the advantages of excitation wavelength-dependent DS single-band emissions and sensitive excitation power-dependent UC multicolor emissions in one and the same material, which has never been reported before. Particularly, the proposed NPs exhibit excellent performance as security labels on trademark tag and security ink on painting, thus revealing the great potential of these lanthanide-doped fluoride NPs in multilevel anti-counterfeiting applications.

CuInS₂ semiconductor nanocrystals (NCs) exhibit large absorption coefficient, size-dependent photoluminescence and low toxicity, making them excellent candidates in a variety of bioapplications. However, precise control of both their composition and morphology to improve the luminescent efficiency remains a great challenge via conventional direct synthesis. Herein, we present a novel low-temperature template synthesis of highly efficient luminescent CuInS₂ nanoprobes from In₂S₃ NCs via a facile cation exchange strategy. The proposed strategy enables synthesis of a series of CuInS₂ NCs with broad size tunability from 2.2 to 29.6 nm. Through rationally manipulating the stoichiometry of Cu/In, highly efficient luminescence of CuInS₂ with the maximum quantum yield of 28.6% has been achieved, which is about one order of magnitude improvement relative to that of directly synthesized NCs. By virtue of the intense emission of CuInS₂ nanoprobes, we exemplify their application in sensitive homogeneous biodetection for an important biomolecule of adenosine triphosphate (ATP) with the limit of detection down to 49.3 nM. Moreover, the CuInS₂ nanoprobes are explored for ATP-targeted cancer cell imaging, thus revealing their great potentials in the field of cancer diagnosis and prognosis.

The accurate detection of blood glucose is of critical importance in the diagnosis and management of diabetes and its complications. Herein, we report a novel strategy based on an upconversion nanoparticles-polydopamine (UCNPs-PDA) nanosystem for the accurate detection of glucose in human serum and whole blood through a simple blending of test samples with ligand-free UCNPs, dopamine, and glucose oxidase (GOx). Owing to the high affinity of lanthanide ions exposed on the surface of ligand-free UCNPs, dopamine monomers could spontaneously attach to the UCNPs and further polymerize to form a PDA shell, resulting in a remarkable upconversion luminescence (UCL) quenching (97.4%) of UCNPs under 980-nm excitation. Such UCL quenching can be effectively inhibited by H₂O₂ produced from the GOx/glucose enzymatic reaction, thus enabling the detection of H₂O₂ or glucose based on the UCL quenching/inhibition bioassay. Owing to the highly sensitive UCL response and background-free interference of the UCNPs-PDA nanosystem, we achieved a sensitive, selective, and high-throughput bioassay for glucose in human serum and whole blood, thereby revealing the great potential of the UCNPs-PDA nanosystem for the accurate detection of blood glucose or other H₂O₂-generated biomolecules in clinical bioassays.

Sensitive detection of cancer biomarker microRNAs (miRNAs) is of vital importance for cancer diagnosis and treatment. Nonetheless, the detection sensitivity in the existing miRNA bioassays is severely limited by the structural characteristics of miRNA (including small length and high sequence homology) because most of these methods are based on target amplification. Herein, we report a novel approach to sensitive and specific detection of low-abundance miRNA via a unique strategy of nanoprobe dissolution-enhanced fluorescence amplification, in which a capture probe featuring molecular beacon structure is designed. By means of this strategy, miRNA-21 was detected in a linear range from 10 fM to 100 pM with a detection limit as low as 1.38 fM. High selectivity of the newly developed biosensor was demonstrated by the good discrimination against a target with a single-base mismatch. Furthermore, this assay was used for the detection of miRNA-21 added into fetal bovine serum samples with the recovery in the range of 90.2%–108% and coefficients of variation below 10.1%, indicating its promising applications to RNA immunoassays and early cancer diagnosis.

Rattle structure is a topic of great interest in design and application of nanomaterials due to the unique core@void@shell architecture and the integration of functions. Herein, we developed a novel "ship-in-a-bottle" method to fabricate upconverting (UC) luminescent nanorattles by incorporating lanthanide-doped fluorides into hollow mesoporous silica. The size of nanorattles and the filling amount of fluorides can be well controlled. In addition, the modification of silica shell (with phenylene and amine groups) and the variation of efficient UC fluorides (NaYF₄: Yb, Er, NaLuF₄: Yb, Er, NaGdF₄: Yb, Er and LiYF₄: Yb, Er) were readily achieved. The resulting nanorattles exhibited a high capacity and pH-dependent release of the anti-cancer drug doxorubicin (DOX). Furthermore, we employed these nanorattles in proof-of-concept UC-monitoring drug release by utilizing the energy transfer process from UC fluorides to DOX, thus revealing the great potential of the nanorattles as efficient cancer theranostic agent.