Showing papers by "Xiaogang Liu published in 2016"

In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics

Abstract: The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

Instantaneous ballistic velocity of suspended Brownian nanocrystals measured by upconversion nanothermometry

Abstract: Luminescence spectroscopy can be employed to investigate the Brownian motion of upconversion nanocrystals with high spatial resolution and thermal sensitivity.

Three-dimensional controlled growth of monodisperse sub-50 nm heterogeneous nanocrystals.

Abstract: The ultimate frontier in nanomaterials engineering is to realize their composition control with atomic scale precision to enable fabrication of nanoparticles with desirable size, shape and surface properties. Such control becomes even more useful when growing hybrid nanocrystals designed to integrate multiple functionalities. Here we report achieving such degree of control in a family of rare-earth-doped nanomaterials. We experimentally verify the co-existence and different roles of oleate anions (OA(-)) and molecules (OAH) in the crystal formation. We identify that the control over the ratio of OA(-) to OAH can be used to directionally inhibit, promote or etch the crystallographic facets of the nanoparticles. This control enables selective grafting of shells with complex morphologies grown over nanocrystal cores, thus allowing the fabrication of a diverse library of monodisperse sub-50 nm nanoparticles. With such programmable additive and subtractive engineering a variety of three-dimensional shapes can be implemented using a bottom-up scalable approach.

Aziridinyl Fluorophores Demonstrate Bright Fluorescence and Superior Photostability by Effectively Inhibiting Twisted Intramolecular Charge Transfer

Abstract: Replacing conventional dialkylamino substituents with a three-membered aziridine ring in naphthalimide leads to significantly enhanced brightness and photostability by effectively suppressing twisted intramolecular charge transfer formation. This replacement is generalizable in other chemical families of fluorophores, such as coumarin, phthalimide, and nitrobenzoxadiazole dyes. In highly polar fluorophores, we show that aziridinyl dyes even outperform their azetidinyl analogues in aqueous solution. We also proposed one simple mechanism that can explain the vulnerability of quantum yield to hydrogen bond interactions in protonic solvents in various fluorophore families. Such knowledge is a critical step toward developing high-performance fluorophores for advanced fluorescence imaging.

Inorganic nanoparticles for optical bioimaging

Abstract: The tremendous progress in the synthesis of different inorganic nanoparticles with pretailored size, shape, structural, compositional, and surface properties has significantly raised their potential applications in biomedicine. Optically active inorganic nanoparticles are those that, based on inorganic materials, can produce fluorescence or scattered light under suitable optical excitation. These outgoing radiations can be conveniently used for bioimaging purposes. In this work, the different types of optically active inorganic nanoparticles that are being used for optical bioimaging are reviewed in detail. Special attention is paid to fluorescent and inorganic persistent luminescence nanoparticles and how their different excitation mechanisms (no-photon, one-photon, or multiphoton excited fluorescence) and working spectral ranges can be conveniently applied for in vitro and in vivo high-contrast optical bioimaging.

Multicolour synthesis in lanthanide-doped nanocrystals through cation exchange in water.

Abstract: Meeting the high demand for lanthanide-doped luminescent nanocrystals across a broad range of fields hinges upon the development of a robust synthetic protocol that provides rapid, just-in-time nanocrystal preparation. However, to date, almost all lanthanide-doped luminescent nanomaterials have relied on direct synthesis requiring stringent controls over crystal nucleation and growth at elevated temperatures. Here we demonstrate the use of a cation exchange strategy for expeditiously accessing large classes of such nanocrystals. By combining the process of cation exchange with energy migration, the luminescence properties of the nanocrystals can be easily tuned while preserving the size, morphology and crystal phase of the initial nanocrystal template. This post-synthesis strategy enables us to achieve upconversion luminescence in Ce3+ and Mn2+-activated hexagonal-phased nanocrystals, opening a gateway towards applications ranging from chemical sensing to anti-counterfeiting.

Remote C-H Activation of Quinolines through Copper-Catalyzed Radical Cross-Coupling.

Abstract: Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a formidable challenge in organic chemistry. Herein, we report a novel approach to activating remote C-H bonds at the C5 position of 8-aminoquinoline through copper-catalyzed sulfonylation under mild conditions. Our strategy shows high conversion efficiency, a broad substrate scope, and good toleration with different functional groups. Furthermore, our mechanistic investigations suggest that a single-electron-transfer process plays a vital role in generating sulfonyl radicals and subsequently initiating C-S cross-coupling. Importantly, our copper-catalyzed remote functionalization protocol can be expanded for the construction of a variety of chemical bonds, including C-O, C-Br, C-N, C-C, and C-I. These findings provide a fundamental insight into the activation of remote C-H bonds, while offering new possibilities for rational design of drug molecules and optoelectronic materials requiring specific modification of functional groups.

Thermal Scanning at the Cellular Level by an Optically Trapped Upconverting Fluorescent Particle.

Abstract: 3D optical manipulation of a thermal-sensing upconverting particle allows for the determination of the extension of the thermal gradient created in the surroundings of a plasmonic-mediated photothermal-treated HeLa cancer cell.

Enabling Förster Resonance Energy Transfer from Large Nanocrystals through Energy Migration.

Abstract: The stringent distance dependence of Forster resonance energy transfer (FRET) has limited the ability of an energy donor to donate excitation energy to an acceptor over a Forster critical distance (R0) of 2–6 nm. This poses a fundamental size constraint (<8 nm or ∼4R0) for experimentation requiring particle-based energy donors. Here, we describe a spatial distribution function model and theoretically validate that the particle size constraint can be mitigated through coupling FRET with a resonant energy migration process. By combining excitation energy migration and surface trapping, we demonstrate experimentally an over 600-fold enhancement over acceptor emission for large nanocrystals (30 nm or ∼15R0) with surface-anchored molecular acceptors. Our work shows that the migration-coupled approach can dramatically improve sensitivity in FRET-limited measurement, with potential applications ranging from facile photochemical synthesis to biological sensing and imaging at the single-molecule level.

Unraveling Epitaxial Habits in the NaLnF4 System for Color Multiplexing at the Single-Particle Level

Abstract: We report an epitaxial growth technique for scalable production of hybrid sodium rare-earth fluoride (NaLnF4 ) microcrystals, including NaYF4 , NaYbF4 , and NaLuF4 material systems. The single crystalline nature of the as-synthesized products makes them strong upconversion emission. The freedom of combining a lanthanide activator (Er(3+) or Tm(3+) ) with a sensitizer (Yb(3+) ) at various doping concentrations readily gives access to color multiplexing at the single-particle level. Our kinetic and thermodynamic investigations on the epitaxial growth of core-shell microcrystals using NaLnF4 particle seeds suggest that within a certain size regime it is plausible to exert precise control over shell thickness and growth orientation under hydrothermal conditions.

Thiazole derivative-modified upconversion nanoparticles for Hg 2+ detection in living cells

Abstract: Mercury ion (Hg2+) is an extremely toxic ion, which will accumulate in human bodies and cause severe nervous system damage. Therefore, the sensitive and efficient monitoring of Hg2+ in human bodies is of great importance. Upconversion nanoparticle (UCNPs) based nano probes exhibit no autofluorescence, deep penetration depth and chemical stability in biological samples, as well as a large anti-stokes shift. In this study, we have developed thiazole-derivative-functionalized UCNPs, and employed an upconversion emission intensity ratio of 540 nm to 803 nm (I540/I803) as a ratiometric signal to detect Hg2+ in living cells showing excellent photo stability and high selectivity. Our nano probe was characterized using transmission electron microscopy (TEM) and powder X-ray diffraction (PXRD). The low cytotoxicity of our probe was confirmed by an MTT assay and the UCL test in HeLa cells was carried out by confocal microscopy. Our results demonstrated that organic-dye-functionalized UCNPs should be a good strategy for detecting toxic metal ions when studying cellular biosystems.

Development of a Highly Selective, Sensitive, and Fast Response Upconversion Luminescent Platform for Hydrogen Sulfide Detection

Abstract: Hydrogen sulfide (H2S) has been recognized as one of most important gaseous signaling molecules mediated by a variety of physiological and pathological processes. Yet, its functions remain largely elusive due to the lack of potent monitoring methods. Hereby this issue is addressed with a powerful new platform—dye-assembled upconversion nanoparticles (UCNPs). A series of chromophores with different absorption bands and fast responses towards H2S is combined with UCNPs and results in a library of H2S sensors with responsive emission signals ranging from the visible to the near-infrared (NIR) region. These nanoprobes demonstrate highly selective and rapid responses to H2S in vitro and in cells. Furthermore, H2S levels in blood can be detected using the developed nanoprobes. Hence the reported H2S sensing platform can serve as a powerful diagnostic tool to research H2S functions and to investigate H2S-related diseases.

Nonlinear spectral and lifetime management in upconversion nanoparticles by controlling energy distribution

Abstract: Optical tuning of lanthanide-doped upconversion nanoparticles has attracted considerable attention over the past decade because this development allows the advance of new frontiers in energy conversion, materials science, and biological imaging. Here we present a rational approach to manipulating the spectral profile and lifetime of lanthanide emission in upconversion nanoparticles by tailoring their nonlinear optical properties. We demonstrate that the incorporation of energy distributors, such as surface defects or an extra amount of dopants, into a rare-earth-based host lattice alters the decay behavior of excited sensitizers, thus markedly improving the emitters’ sensitivity to excitation power. This work provides insight into mechanistic understanding of upconversion phenomena in nanoparticles and also enables exciting new opportunities of using these nanomaterials for photonic applications.

Optical Torques on Upconverting Particles for Intracellular Microrheometry

Abstract: Precise knowledge and control over the orientation of individual upconverting particles is extremely important for full exploiting their capabilities as multifunctional bioprobes for interdisciplinary applications. In this work, we report on how time-resolved, single particle polarized spectroscopy can be used to determine the orientation dynamics of a single upconverting particle when entering into an optical trap. Experimental results have unequivocally evidenced the existence of a unique stable configuration. Numerical simulations and simple numerical calculations have demonstrated that the dipole magnetic interactions between the upconverting particle and trapping radiation are the main mechanisms responsible of the optical torques that drive the upconverting particle to its stable orientation. Finally, how a proper analysis of the rotation dynamics of a single upconverting particle within an optical trap can provide valuable information about the properties of the medium in which it is suspended is d...

Multilayer Dye Aggregation at Dye/TiO2 Interface via π…π Stacking and Hydrogen Bond and Its Impact on Solar Cell Performance: A DFT Analysis.

Abstract: Multilayer dye aggregation at the dye/TiO2 interface of dye-sensitized solar cells is probed via first principles calculations, using p-methyl red azo dye as an example. Our calculations suggest that the multilayer dye aggregates at the TiO2 surface can be stabilized by π…π stacking and hydrogen bond interactions. Compared with previous two-dimensional monolayer dye/TiO2 model, the multilayer dye aggregation model proposed in this study constructs a three-dimensional multilayer dye/TiO2 interfacial structure, and provides a better agreement between experimental and computational results in dye coverage and dye adsorption energy. In particular, a dimer forms by π…π stacking interactions between two neighboring azo molecules, while one of them chemisorbs on the TiO2 surface; a trimer may form by introducing one additional azo molecule on the dimer through a hydrogen bond between two carboxylic acid groups. Different forms of multilayer dye aggregates, either stabilized by π…π stacking or hydrogen bond, exhibit varied optical absorption spectra and electronic properties. Such variations could have a critical impact on the performance of dye sensitized solar cells.

First-Principles Study of Molecular Adsorption on Lead Iodide Perovskite Surface: A Case Study of Halogen Bond Passivation for Solar Cell Application

Abstract: Organic molecules have recently been used to modify the surface/interface structures of lead halide perovskite solar cells to enhance device performance. Yet, the detailed interfacial structures and adsorption mechanism of the molecular modified perovskite surface remain elusive. This study presents a nanoscopic structural view on how organic molecules interact with the perovskite surface. We focus on the halogen bond passivated lead iodide perovskite surface, based on first-principles calculations. Our calculations show that organic molecules can interact with the perovskite surface via halogen bonds, which modifies the interfacial structures of the perovskite surface. We also constructed a detailed potential energy surface of the perovskite surface by moving the adsorbed molecule along different axes of the unit cell in order to comprehensively understand perovskite surface structures. This study demonstrates the effectiveness of modifying the perovskite surface structure via a molecular adsorption appr...

Designing Upconversion Nanocrystals Capable of 745 nm Sensitization and 803 nm Emission for Deep‐Tissue Imaging

Abstract: A crystal design strategy is described that generates hexagonal-phased NaYF4 :Nd/Yb@NaYF4 :Yb/Tm luminescent nanocrystals with the ability to emit light at 803 nm when illuminated at 745 nm. This is accomplished by taking advantage of the large absorption cross-section of Nd(3+) between 720 and 760 nm plus efficient spatial energy transfer and migration through Nd(3+) →Yb(3+) →Yb(3+) →Tm(3+) . Mechanistic investigations suggest that a cascaded two-photon energy transfer upconversion process underlies the emission mechanism. This protocol enables deep-tissue imaging to be achieved while mitigating the attenuation effect associated with the visible emission and the overheating constraint imposed by conventional 980 nm excitation.

Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease.

Abstract: The objective of this study was to identify novel causal genes involved in the pathogenesis of Kashin-Beck disease (KBD). A representative grade III KBD sib pair with serious skeletal growth and development failure was subjected to exome sequencing using the Illumina Hiseq2000 platform. The detected gene mutations were then filtered against the data of 1000 Genome Project, dbSNP database, and BGI inhouse database, and replicated by a genome-wide association study (GWAS) of KBD. Ninety grade II or III KBD patients with extreme KBD phenotypes and 1627 healthy controls were enrolled in the GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was applied for genotyping. PLINK software was used for association analysis. We identified a novel 106T>C at the 3'UTR of the FGF12 gene, which has not been reported by now. Sequence alignment observed high conversation at the mutated 3'UTR+106T>C locus across various vertebrates. In the GWAS of KBD, we detected nine SNPs of the FGF12 gene showing association evidence (P value < 0.05) with KBD. The most significant association signal was observed at rs1847340 (P value = 1.90 × 10(-5)). This study suggests that FGF12 was a susceptibility gene of KBD. Our results provide novel clues for revealing the pathogenesis of KBD and the biological function of FGF12.

A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease

Abstract: Kashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value = 9.25 × 10−9) with the KBD. Replication study observed significant association signal at rs1278300 (p-value = 0.007) and rs1710287 (p-value = 0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate = 47.59 ± 7.79%) compared to healthy articular cartilage (average positive chondrocyte rate = 64.73 ± 5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD.

Catalysis to Build Molecular Complexity with Atomic Precision.

Abstract: The smaller, the better: Catalysis takes many forms and has a vast number of applications. Be it heterogeneous or homogeneous, organic, transition-metal or biocatalysis, the many facets of the discipline enable efficient synthetic routes and open up new avenues to previously inaccessible compounds. This special issue is about the catalysis and transformation of complex molecules.

High-Precision Pinpointing of Luminescent Targets in Encoder-Assisted Scanning Microscopy Allowing High-Speed Quantitative Analysis

Abstract: Compared with routine microscopy imaging of a few analytes at a time, rapid scanning through the whole sample area of a microscope slide to locate every single target object offers many advantages in terms of simplicity, speed, throughput, and potential for robust quantitative analysis. Existing techniques that accommodate solid-phase samples incorporating individual micrometer-sized targets generally rely on digital microscopy and image analysis, with intrinsically low throughput and reliability. Here, we report an advanced on-the-fly stage scanning method to achieve high-precision target location across the whole slide. By integrating X- and Y-axis linear encoders to a motorized stage as the virtual “grids” that provide real-time positional references, we demonstrate an orthogonal scanning automated microscopy (OSAM) technique which can search a coverslip area of 50 × 24 mm2 in just 5.3 min and locate individual 15 μm lanthanide luminescent microspheres with standard deviations of 1.38 and 1.75 μm in X ...

PPARGC1B gene is associated with Kashin-Beck disease in Han Chinese.

Abstract: Kashin-Beck disease (KBD) is a chronic osteochondropathy. The genetic basis of KBD remains elusive now. To investigate the relationship between PPARGC1B gene polymorphism and KBD, we conducted a two-stage association study using 2743 unrelated Han Chinese subjects. In the first stage, three SNPs rs1078324, rs4705372, and rs11743128 of PPARGC1B gene were genotyped in 559 KBD patients and 467 health controls using Sequenom MassARRAY platform. In the second stage, the association analysis results of PPARGC1B with KBD were replicated using an independent sample of 1717 subjects. SNP association analysis was conducted by PLINK software. Genotype imputation was conducted by IMPUTE 2.0 against the reference panel of the 1000 genome project. Bonferroni multiple testing correction was performed. We observed a significant association signal at rs4705372 (P = 0.0160) and a suggestive association signal at rs11743128 (P = 0.0290). Further replication study confirmed the association signals of rs4705372 (P = 0.0026) and rs11743128 (P = 0.0387) in the independent validation sample. Our study results suggest that PPARGC1B is a novel susceptibility gene of KBD.

Remote C—H Activation of Quinolines Through Copper‐Catalyzed Radical Cross‐Coupling.

Abstract: Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a formidable challenge in organic chemistry. Herein, we report a novel approach to activating remote C-H bonds at the C5 position of 8-aminoquinoline through copper-catalyzed sulfonylation under mild conditions. Our strategy shows high conversion efficiency, a broad substrate scope, and good toleration with different functional groups. Furthermore, our mechanistic investigations suggest that a single-electron-transfer process plays a vital role in generating sulfonyl radicals and subsequently initiating C-S cross-coupling. Importantly, our copper-catalyzed remote functionalization protocol can be expanded for the construction of a variety of chemical bonds, including C-O, C-Br, C-N, C-C, and C-I. These findings provide a fundamental insight into the activation of remote C-H bonds, while offering new possibilities for rational design of drug molecules and optoelectronic materials requiring specific modification of functional groups.