Facile Synthesis of Mg2+‐Doped Carbon Dots as Novel Biomaterial Inducing Cell Osteoblastic Differentiation

Carbon dots (CDs), as an emerging fluorescent nanomaterial with low toxicity, has been widely applied in various bio‐related fields. However, investigations on their capabilities in guiding osteogenic differentiation are rarely seen, which has great significance in osteoporosis therapy and bone regeneration. Herein, for the first time, a new kind of Mg²⁺‐doped CDs is facilely synthesized through a one‐step hydrothermal method from metal gluconate salts. The CDs can serve as nanocarrier of Mg²⁺ ions entering into cells, and the bioessential metal ions subsequently stimulate osteoblastic differentiation by improving alkaline phosphatase (ALP) activity and upregulation related mRNA expression. Noteworthy, the raw material has almost negligible performance on osteoblastic differentiation compared to Mg‐CDs, which is due to the ultrasmall sizes of CDs and the efficient uptake by cells. Moreover, benefitting from the fluorescence properties, Mg‐CDs can also be applied as cell labeling agents. This work proposes a new strategy to synthesize multifunctional metal ion‐doped CDs, which might had great potential in serving as promising nanodrugs for bone loss therapy.     

Overview of Syntheses and Molecular-Design Strategies for Tetrazine-Based Fluorogenic Probes

Various bioorthogonal chemistries have been used for fluorescent imaging owing to the advantageous reactions they employ. Recent advances in bioorthogonal chemistry have revolutionized labeling strategies for fluorescence imaging, with inverse electron demand Diels–Alder (iEDDA) reactions in particular attracting recent attention owing to their fast kinetics and excellent specificity. One of the most interesting features of the iEDDA labeling strategy is that tetrazine-functionalized dyes are known to act as fluorogenic probes. In this review, we will focus on the synthesis, molecular-design strategies, and bioimaging applications of tetrazine-functionalized fluorogenic probes. Traditional Pinner reaction and “Pinner-like” reactions for tetrazine synthesis are discussed here, as well as metal-catalyzed C–C bond formations with convenient tetrazine intermediates and the fabrication of tetrazine-conjugated fluorophores. In addition, four different quenching mechanisms for tetrazine-modified fluorophores are presented.     

Novel CD-MOF NIR-II fluorophores for gastric ulcer imaging

Gastric ulcers are one of the most common stomach diseases that often accompanied by inflammation, congestion, edema, scar tissue formation, and pyloric obstruction. Fiberoptic endoscopy and X-ray analysis of the upper GI tract have become the diagnostic procedure of choice for patients. However, conventional diagnosis technology is either invasive or radioactive. Herein, a novel CD-MOF NIR-II fluorophore (GPs-CH1055) was developed. The relative fluorophore intensity was largely consistent at various media and pH buffers, and it can swell into gel particles in solvents and be completely expelled from the gastrointestinal tract without being assimilated. GPs-CH1055 has been further evaluated in vivo, and exhibited strong retention effect on the gastric ulcer sites, bright NIR-II signals with high spatial and temporal resolution. Therefore, GPs-CH1055 shows great promise for realizing real-time gastric ulcer imaging and diagnosis.     

3,4-Dinitrobenzamide Functionalized CdTe/ZnTe Quantum Dots as a Nanoprobe for Imaging Glutathione S-Transferase in Living Cells

A novel fluorescent nanoprobe for glutathione S‐transferase (GST) has been developed by incorporating 3,4‐dinitrobenzamide (a specific substrate of GST) onto CdTe/ZnTe quantum dots. The probe itself displays a low background signal due to the strong quenching effect of the electron‐withdrawing unit of 3,4‐dinitrobenzamide on the quantum dots. However, GST can efficiently catalyze the nucleophilic substitution of reduced glutathione on the p‐nitro group of the nanoprobe, leading to a large fluorescence enhancement. Most notably, this enhancement shows high selectivity and sensitivity towards GST instead of the other biological substances. With this nanoprobe, a simple fluorescence imaging method for intracellular GST has been established, and its applicability has been successfully demonstrated for imaging GST in different living cells, which reveals that A549 cells express GST about 3 times higher than NIH‐3T3 and Hela cells.     

Rational Design of an “OFF–ON” Phosphorescent Chemodosimeter Based on an Iridium(III) Complex and Its Application for Time‐Resolved Luminescent Detection and Bioimaging of Cysteine and Homocysteine

Biothiols, such as cysteine (Cys) and homocysteine (Hcy), play very crucial roles in biological systems. Abnormal levels of these biothiols are often associated with many types of diseases. Therefore, the detection of Cys (or Hcy) is of great importance. In this work, we have synthesized an excellent “OFF‐ON” phosphorescent chemodosimeter 1 for sensing Cys and Hcy with high selectivity and naked‐eye detection based on an Ir^III complex containing a 2,4‐dinitrobenzenesulfonyl (DNBS) group within its ligand. The “OFF‐ON” phosphorescent response can be assigned to the electron‐transfer process from Ir^III center and C^N ligands to the DNBS group as the strong electron‐acceptor, which can quench the phosphorescence of probe 1 completely. The DNBS group can be cleaved by thiols of Cys or Hcy, and both the ³M LCT and ³LC states are responsible for the excited‐state properties of the reaction product of probe 1 and Cys (or Hcy). Thus, the phosphorescence is switched on. Based on these results, a general principle for designing “OFF‐ON” phosphorescent chemodosimeters based on heavy‐metal complexes has been provided. Importantly, utilizing the long emission‐lifetime of phosphorescence signal, the time‐resolved luminescent assay of 1 in sensing Cys was realized successfully, which can eliminate the interference from the short‐lived background fluorescence and improve the signal‐to‐noise ratio. As far as we know, this is the first report about the time‐resolved luminescent detection of biothiols. Finally, probe 1 has been used successfully for bioimaging the changes of Cys/Hcy concentration in living cells.     

Controlled Click‐Assembly of Well‐Defined Hetero‐Bifunctional Cubic Silsesquioxanes and Their Application in Targeted Bioimaging

A general procedure for the assembly of hetero‐bifunctional cubic silsesquioxanes with diverse functionality and a perfectly controlled distribution of functional groups on the inorganic framework has been developed. The method is based on a two‐step sequence of mono‐ and hepta‐functionalization through the ligand‐accelerated copper(I)‐catalyzed azide–alkyne cycloaddition of a readily available octaazido cubic silsesquioxane. The stoichiometry of the reactants and the law of binomial distribution essentially determine the selectivity of the key monofunctionalization reaction when a copper catalyst with strong donor ligands is used. The methodology has been applied to the preparation of a set of bifunctional nano‐building‐blocks with orthogonal reactivity for the controlled assembly of precisely defined hybrid nanomaterials and a fluorescent multivalent probe for application in targeted cell‐imaging. The inorganic cage provides an improved photostability to the covalently attached dye as well as a convenient framework for the 3D multivalent display of the pendant epitopes. Thus, fluorescent bioprobes based on well‐defined cubic silsesquioxanes offer interesting advantages over more conventional fully organic analogues and ill‐defined hybrid nanoparticles and promise to become powerful tools for the study of cell biology and for biomedical applications.     

Carbon Dots Prepared by Hydrothermal Treatment of Dopamine as an Effective Fluorescent Sensing Platform for the Label‐Free Detection of Iron(III) Ions and Dopamine

A facile, economic and green one‐step hydrothermal synthesis route using dopamine as source towards photoluminescent carbon nanoparticles (CNPs) is proposed. The as‐prepared CNPs have an average size about 3.8 nm. The emission spectra of the CNPs are broad, ranging from approximately 380 (purple) to approximately 525 nm (green), depending on the excitation wavelengths. Due to the favorable optical properties, the CNPs can readily enter into A549 cells and has been used for multicolor biolabeling and bioimaging. Most importantly, the as‐prepared CNPs contain distinctive catechol groups on their surfaces. Due to the special response of catechol groups to Fe³⁺ ions, we further demonstrate that such wholly new CNPs can serve as a very effective fluorescent sensing platform for label‐free sensitive and selective detection of Fe³⁺ ions and dopamine with a detection limit as low as 0.32 μM and 68 nM , respectively. The new “mix‐and‐detect” strategy is simple, green, and exhibits high sensitivity and selectivity. The present method was also applied to the determination of Fe³⁺ ions in real water samples and dopamine in human urine and serum samples successfully.     

共轭聚合物荧光纳米粒子研究进展

近年来,共轭聚合物荧光纳米粒子因其优异的光学性能,在化学、医学和环境科学等研究领域显示了极其广阔的应用前景.相比于传统无机半导体荧光纳米材料,共轭聚合物荧光纳米粒子具有结构多样性、功能可设计性、生物相容性好等显著优势.本文从共轭聚合物荧光粒子的制备方法、光学性能、表面功能化修饰出发,重点讨论了近年来共轭聚合物纳米粒子作为荧光探针在细胞成像及生物化学检测方面的研究进展,阐述了当前研究的主要发展方向和仍需解决的问题.     

o‐Fluorination of Aromatic Azides Yields Improved Azido‐Based Fluorescent Probes for Hydrogen Sulfide: Synthesis,Spectra, and Bioimaging

Hydrogen sulfide (H₂S) is an endogenously produced gaseous signaling molecule with multiple biological functions. To visualize the endogenous in situ production of H₂S in real time, new coumarin‐ and boron‐dipyrromethene‐based fluorescent turn‐on probes were developed for fast sensing of H₂S in aqueous buffer and in living cells. Introduction of a fluoro group in the ortho position of the aromatic azide can lead to a greater than twofold increase in the rate of reaction with H₂S. On the basis of o‐fluorinated aromatic azides, fluorescent probes with high sensitivity and selectivity toward H₂S over other biologically relevant species were designed and synthesized. The probes can be used to in situ to visualize exogenous H₂S and D ‐cysteine‐dependent endogenously produced H₂S in living cells, which makes them promising tools for potential applications in H₂S biology.