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Organic and polymer fluorescent nanomaterials are a frontier research focus. Here in this work, a series of fluorinated zwitterionic random copolymers end‐attached with a quasi‐chromophoric group of pyrene or tetraphenylethylene (TPE) are well synthesized via atom transfer radical polymerization with activators regenerated by electron transfer (ARGET ATRP). Those random copolymers with total degree of polymerization 100 or 200 are able to produce fluorescent single‐chain nanoparticles (SCNPs) through intra‐chain self‐folding assembly with quite uniform diameters in the range of 10–20 nm as characterized by dynamic light scattering and transmission electron microscopy. By virtue of the segregation or confinement effect, both SCNPs functionalized with pyrene or TPE group are capable of emitting fluorescence, with pyrene tethered SCNPs exhibiting stronger fluorescence emission reaching the highest quantum yield ≈20%. Moreover, such kind of fluorescent SCNPs manifest low cytotoxicity and good cell imaging performance for Hela cells. The creation of fluorescent SCNPs through covalently attached one quasi‐chromophore to the end of one fluorinated zwitterionic random copolymer provides an alternative strategy for preparing polymeric luminescence nanomaterials, promisingly serving as a new type of fluorescent nanoprobes for biological imaging applications. [ABSTRACT FROM AUTHOR]

A series of functional glycopolymer nanoparticles with 1,8‐naphthalimide motif was designed, synthesized and applied for tumor cell imaging. With the pH‐sensitive and aggregation‐induced emission (AIE) effect of the 1,8‐naphthalimide fluorescent probe, the presence of glucose‐based glycopolymers enhanced its water‐solubility and biocompatibility. Owing to the dual tumor‐targeting effects of the dense glucose part and the boronic ester modification, the obtained glycopolymers showed high affinity to tumor cells, with a much faster staining rate than normal cells, indicating a great potential for diagnosis and treatments of cancers. [ABSTRACT FROM AUTHOR]

A light controllable two‐photon near‐infrared (NIR) optical probe is conveniently constructed by multivalent supramolecular co‐assembly of amphiphilic sulfonatocalix[4]arene (SC4A), tricationic triphenylamine (TPA), and diarylethene derivative (DE). The obtained results indicate that the formed SC4A/TPA nanoparticle displays assemble‐confined behaviors and enhances the two‐photon excited NIR emission. Benefiting from the reversible ring‐opened and closed behaviors of the DE under 365 and > 600 nm light irradiation, the dicationic DE in the assembly could act as an energy acceptor after 365 nm light irradiation, then the co‐assembly of SC4A/TPA/DE could achieve a NIR fluorescence ON and OFF switch and is successfully applied in HeLa cell imaging, providing a convenient approach to supramolecular two‐photon switch for cell imaging. [ABSTRACT FROM AUTHOR]

Supramolecular luminescent nano‐assemblies for cell imaging have recently attracted increasing interest, not only because of their outstanding photophysical properties, but also because of their easy fabrication through supramolecular strategies, good biocompatibility, high stability to photo‐ and micro‐environments in cells, and facile combination of imaging and synergistic therapy for cancers. Luminescence‐based bioimaging has great advantages, such as high sensitivity, being non‐invasive, and functioning in real‐time, leading to its wide application in many fields, including disease research, drug research, cell markers, gene expression, gene function studies, and protein interaction. In this Review, recent progress in the application of macrocycle‐mediated (e.g. cyclodextrins, cucurbiturils, calixarenes, and pillar[n]arenes) and functionalized amphiphilic molecule‐based supramolecular luminescent nanoparticles in cell imaging, especially targeted cell imaging of specific organelles, is reviewed. The combination of imaging with drug delivery, gene delivery, and photodynamic therapy is also introduced. [ABSTRACT FROM AUTHOR]

In nanomedicine, lipid‐based nanoparticles (NPs) such as liposomes (LPs) have established an important position. Precise delineation of NP interaction with cells and detailed characterization of activity are becoming essential, which mainly rely on labeling with lipophilic fluorescent molecules and assuming stable association with NPs. However, because of label separation from NPs in (biological) media, or when processed by cells, fluorescence‐based detection of an NP incorporating a single label may not necessarily indicate the actual presence of an NP but may be from the dissociated label, rendering results unreliable. Herein, flow cytometry and confocal microscopy are employed to demonstrate that to verify the localization of LPs in a cell with perfect accuracy, dual‐labeling, and contemporaneous detection of both fluorescent signals in one pixel are required. This is combined with size exclusion chromatography (SEC) and mass spectrometry measurements to indicate factors involved in label dissociation, which helps to understand the possible conditions of dissociated label and NP. It is shown that determining label colocalization with, and label dissociation from, dual‐labeled NPs are needed to provide accurate spatiotemporal insight into targeting destination (colocalized signals) and disintegration (separated signals) of NPs during intracellular processing and in studying payload delivery with precision in nanomedicine. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Nanofluorophores based on aggregation‐induced emission (AIE) dyes have recently received considerable attention because of their unique optical properties and biocompatibility. In this work, we report an emission‐tunable nanofluorophore constructed by the self‐assembly of an amphiphilic block copolymer (denoted by PTN). The diblock copolymer was synthesized by RAFT polymerization. A polyethylene glycol‐based trithiocarbonate was employed as the macromolecular chain transfer agent, and a near‐infrared emitting tetraphenylethylene derivative with a vinyl terminal group was designed as the monomer. The block copolymers self‐assembled in an aqueous solution to form nanospheres, which showed near‐infrared emission at approximately 720 nm with a significant Stokes shift of approximately 260 nm. Furthermore, nanofluorophores have excellent biocompatibility, photostability, and pH‐independent emission‐tunable properties, and were successfully applied to label HeLa cells for fluorescence imaging. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) imaging in disease sites is vital to elucidate their role in cancer progression. However, limited tumor specificity remains a major barrier for traditional amplification approaches due to associated background signal leakage. Here, we report a generalizable approach via the combination of enzymatically triggered catalytic hairpin assembly with lipid nanoparticles (LNPs)‐based delivery strategy for tumor‐specific activation of signal amplification and therefore sensitive miRNA imaging. The signal amplification is established via engineering of traditional catalytic hairpin assembly with enzymatically activated motifs to achieve triggable miRNA imaging in cancer cells. Furthermore, by the introduction of LNPs to combat biological barriers, we demonstrate that the system enables amplified miRNA imaging in vivo with reduced off‐tumor signal, leading to enhanced tumor‐to‐background contrast compared with traditional methods. This approach that relies on specific triggers and controlled delivery to distinguish miRNA in cancer cells from normal cells should be useful in tumor diagnosis. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) imaging in disease sites is vital to elucidate their role in cancer progression. However, limited tumor specificity remains a major barrier for traditional amplification approaches due to associated background signal leakage. Here, we report a generalizable approach via the combination of enzymatically triggered catalytic hairpin assembly with lipid nanoparticles (LNPs)‐based delivery strategy for tumor‐specific activation of signal amplification and therefore sensitive miRNA imaging. The signal amplification is established via engineering of traditional catalytic hairpin assembly with enzymatically activated motifs to achieve triggable miRNA imaging in cancer cells. Furthermore, by the introduction of LNPs to combat biological barriers, we demonstrate that the system enables amplified miRNA imaging in vivo with reduced off‐tumor signal, leading to enhanced tumor‐to‐background contrast compared with traditional methods. This approach that relies on specific triggers and controlled delivery to distinguish miRNA in cancer cells from normal cells should be useful in tumor diagnosis. [ABSTRACT FROM AUTHOR]

Fluorescent polymer nanoparticles (NPs) have great potential as bioimaging and therapeutic agents in the biomedical field. Here, a subtle method is developed to synthesize inherently fluorescent core–shell NPs with diameters less than 100 nm. The permanent fluorescence comes from the rigid conjugated structure between benzene and chloromethyl groups in the crosslinked poly(chloromethylstyrene) (PCMSt) core, which is able to be applied for the determination of Fe3+ with a detection limit of 1.39 × 10−6 m. It is further demonstrated that the galactose modification (poly (6‐O‐acryloyl‐d‐galactose), PADGal) shell can efficiently· facilitate the selective internalization of NPs by human hepatocellular carcinoma cells (HepG2), and the cells are more prone to uptake the NPs with medium crosslinking degree. The hydrophobic anticancer drug 10‐hydroxycamptothecin (HCPT) is then loaded onto PADGal@PCMSt NPs. Benefiting from the specific interactions between asialoglycoprotein (ASGP) receptors and the galactose moiety, the PADGal@PCMSt NPs can deliver HCPT with the highest efficiency to HepG2 cells in comparison with the human cervical cancer cells (HeLa), the human alveolar adenocarcinoma basal epithelial cells (A549), the mouse breast cancer cells (4T1), and the mouse fibroblast cells (NIH3T3). The present study provides a new strategy to build small‐size fluorescent polymer NPs with both bioimaging and therapeutic functions. [ABSTRACT FROM AUTHOR]

Simultaneous imaging of multiple microRNAs (miRNAs) in individual living cells is challenging due to the lack of spectrally distinct encoded fluorophores and non‐cytotoxic methods. We describe a multiplexed error‐robust combinatorial fluorescent label‐encoding method, termed fluorophores encoded error‐corrected labels (FluoELs), enabling multiplexed miRNA imaging in living cells with error‐correcting capability. The FluoELs comprise proportional dual fluorophores for encoding and a constant quantitative single fluorophore for error‐corrected quantification. Both are embedded in 260 nm core–shell silica nanoparticles modified with molecular beacon detection probes. The FluoELs are low cytotoxic and could accurately quantify and spatially resolve nine breast‐cancer‐related miRNAs and evaluate their coordination. The FluoELs enabled a single‐cell analysis platform to evaluate miRNA expression profiles and the molecular mechanisms underlying miRNA‐associated diseases. [ABSTRACT FROM AUTHOR]

Simultaneous imaging of multiple microRNAs (miRNAs) in individual living cells is challenging due to the lack of spectrally distinct encoded fluorophores and non‐cytotoxic methods. We describe a multiplexed error‐robust combinatorial fluorescent label‐encoding method, termed fluorophores encoded error‐corrected labels (FluoELs), enabling multiplexed miRNA imaging in living cells with error‐correcting capability. The FluoELs comprise proportional dual fluorophores for encoding and a constant quantitative single fluorophore for error‐corrected quantification. Both are embedded in 260 nm core–shell silica nanoparticles modified with molecular beacon detection probes. The FluoELs are low cytotoxic and could accurately quantify and spatially resolve nine breast‐cancer‐related miRNAs and evaluate their coordination. The FluoELs enabled a single‐cell analysis platform to evaluate miRNA expression profiles and the molecular mechanisms underlying miRNA‐associated diseases. [ABSTRACT FROM AUTHOR]

The interrogation of metabolic parameters like pH in live‐cell experiments using optical super‐resolution microscopy (SRM) remains challenging. This is due to a paucity of appropriate metabolic probes enabling live‐cell SRM‐based sensing. Here, ultrasmall fluorescent core–shell aluminosilicate nanoparticle sensors (FAM–ATTO647N aC′ dots) that covalently encapsulate a reference dye (ATTO647N) in the core and a pH‐sensing moiety (FAM) in the shell are introduced. Only the reference dye exhibits optical blinking enabling live‐cell stochastic optical reconstruction microscopy (STORM). Using data from cells incubated for 60 min with FAM–ATTO647N aC′ dots, pixelated information from total internal reflection fluorescence (TIRF) microscopy‐based ratiometric sensing can be combined with that from STORM‐based localizations via the blinking reference dye in order to enhance the resolution of ratiometric pH sensor maps beyond the optical diffraction limit. A nearest‐neighbor interpolation methodology is developed to quantitatively address particle compositional heterogeneity as determined by separate single‐particle fluorescence imaging methods. When combined with STORM‐based estimates of the number of particles per vesicle, vesicle size, and vesicular motion as a whole, this analysis provides detailed live‐cell spatial and functional information, paving the way to a comprehensive mapping and understanding of the spatiotemporal evolution of nanoparticle processing by cells important, e.g., for applications in nanomedicine. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: The intracellular delivery of metal‐organic frameworks (MOFs) encapsulated with functional biomolecules represents a promising avenue in the field of biomedicine and biosensing. To improve the cellular uptake efficiency of MOFs, here we report the fabrication of cancer cell‐derived exosome membrane (EM)‐coated zeolitic imidazolate framework‐8 (EM‐ZIF‐8) nanoparticles by using a microfluidic sonication device. EM‐ZIF‐8 nanoparticles loaded with FITC‐labeled bovine serum albumin (BSA) can be taken up by cancer cells and evade phagocytosis more efficiently than their counterparts (ZIF‐8 nanoparticles). Moreover, we use EM‐ZIF‐8 loaded with Rhodamine B (RhB) for in situ imaging of cellular adenosine triphosphate (ATP). The shield effect of ZIF‐8 suppresses the fluorescence of RhB, and the presence of ATP disrupts the ZIF‐8 structure based on the competitive coordination between ATP and Zn2+, leading to the restoration of RhB fluorescence. This method allows accurate detection of the fluctuation of ATP in A549 cells induced by Ca2+ or 2‐DDG treatment. The devised biomimetic EM‐ZIF‐8 nanoparticles thus provide an efficient platform for intracellular drug delivery and ATP sensing. [ABSTRACT FROM AUTHOR]

Stem cell therapy has been used as a potential approach for the treatment of myocardial infarction (MI) over the last two decades. Imaging cellular behaviors of the transplanted stem cells with deep tissue penetration and high precision imaging modalities is crucial for the clinical translation of stem cell therapy approaches for MI. Herein, a gold nanostar (Au‐Star) based second near‐infrared window (NIR‐II) fluorescence/surface enhanced Raman scattering dual‐modal imaging probe (gold nanostar‐3.3′‐diethylthiatricarbocyanine iodide‐silver sulfide nanoparticles, Au‐Star‐DTTC‐Ag2S NPs, GDS NPs) is designed for labeling and precise tracking of the stem cells. The Ag2S compartment generates strong NIR‐II emission, which compensates for the deficiencies of bioluminescent imaging and enables the dynamic observation of in vivo cellular behavior. Subsequently, the specific Raman signal of Au‐Star‐DTTC compartment enables high‐resolution imaging, which could effectively delineate stem cells from the surrounding normal tissues, even at a single‐cell resolution. Using this imaging and tracking approach, it is able to track stem cells in hypodermic and MI models, with high resolution and depth‐independent imaging capabilities, which have not been reported in any other cell tracking platform. This two‐armed imaging toolkit offers new opportunities for a wide range of mechanistic stem cell therapy investigations in different organs. [ABSTRACT FROM AUTHOR]

A recent research article published in Angewandte Chemie by Rachel C. Evans et al. explores the use of ultra-small nanoparticle probes for anti-Stokes fluorescence lifetime imaging in living cells. The researchers designed these probes using triplet-triplet annihilation upconversion (TTA-UC) chromophores encapsulated in an organic-inorganic ureasil host. The study demonstrates that these nanoparticles can be used to map local oxygen diffusion across the subcellular structure, as evidenced by fluctuations in the upconversion lifetime in stained cells. The authors of the article include Bolong Zhang, Kieran D. Richards, Beatrice E. Jones, Abigail R. Collins, Rosie Sanders, Sarah R. Needham, Pu Qian, Amoghavarsha Mahadevegowda, Caterina Ducati, Stanley W. Botchway, and Rachel C. Evans. [Extracted from the article]

In a research article published in Angewandte Chemie International Edition, Rachel C. Evans et al. demonstrate the use of ultra-small nanoparticle probes for anti-Stokes fluorescence lifetime imaging in living cells. These probes are based on triplet-triplet annihilation upconversion (TTA-UC) chromophores encapsulated in an organic-inorganic ureasil host. The researchers found that the nanoparticles can be used to map local oxygen diffusion across the subcellular structure, as indicated by fluctuations in the upconversion lifetime in stained cells. The study provides valuable insights into the potential applications of these nanoparticles in imaging techniques. [Extracted from the article]

A robust platform is developed to assemble sub‐10 nm organic aggregation‐induced emission (AIE) particles using four different AIE luminogens (AIEgens) with emissions from green to the second near‐infrared window (NIR‐II). They are called AIE quantum dots (QDs) to distinguish from typical AIE dots which are larger than 25 nm. Compared with AIE dots that are larger than 25 nm, AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane‐penetrating peptides or other targeting molecules. NIR‐II AIEgens, which have nearly no background fluorescence from organisms, are used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80 mm3 and evade the liver more efficiently than AIE dots. AIE QDs hold a good promise for sensitive and precise diagnosis of the latent solid tumor in clinical medicine with much lower off‐targeting to the liver than AIE dots. [ABSTRACT FROM AUTHOR]

A robust platform is developed to assemble sub‐10 nm organic aggregation‐induced emission (AIE) particles using four different AIE luminogens (AIEgens) with emissions from green to the second near‐infrared window (NIR‐II). They are called AIE quantum dots (QDs) to distinguish from typical AIE dots which are larger than 25 nm. Compared with AIE dots that are larger than 25 nm, AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane‐penetrating peptides or other targeting molecules. NIR‐II AIEgens, which have nearly no background fluorescence from organisms, are used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80 mm3 and evade the liver more efficiently than AIE dots. AIE QDs hold a good promise for sensitive and precise diagnosis of the latent solid tumor in clinical medicine with much lower off‐targeting to the liver than AIE dots. [ABSTRACT FROM AUTHOR]

A method is developed to fabricate tumor microenvironment (TME) stimuli‐responsive nanoplatform for fluorescence (FL) imaging and synergistic cancer therapy via assembling photosensitizer (chlorine e6, Ce6) modified carbon dots (CDs‐Ce6) and Cu2+. The as‐obtained nanoassemblies (named Cu/CC nanoparticles, NPs) exhibit quenched FL and photosensitization due to the aggregation of CDs‐Ce6. Their FL imaging and photodynamic therapy (PDT) functions are recovered efficiently once they entering tumor sites by the stimulation of TME. Introducing of Cu2+ not only provides extra chemodynamic therapy (CDT) function through reaction with hydrogen peroxide (H2O2), but also depletes GSH in tumors by a redox reaction, thus amplifying the intracellular oxidative stress and enhancing the efficacy of reactive oxygen species (ROS) based therapy. Cu/CC NPs can act as a FL imaging guided trimodal synergistic cancer treatment agent by photothermal therapy (PTT), PDT, and thermally amplified CDT. [ABSTRACT FROM AUTHOR]

Photoswitchable luminescent supramolecular assemblies based on cyclodextrins have attracted considerable attention owing to their potential applications as smart materials, but most of the assemblies reported to date emit green or blue light with low contrast and high interference. In this study, novel photoluminescent red‐luminescent quaternary supramolecular nanoparticles (2) are constructed from a dithienylethene derivative (1), a β‐cyclodextrin‐functionalized ruthenium complex (Ru‐HOP‐CD), Pluronic F‐127, and cetrimonium bromide. Compared with the binary assembly 1@Ru‐HOP‐CD, the quaternary nanoparticles exhibit high fluorescence resonance energy transfer efficiency, with Ru‐HOP‐CD acting as the donor and 1 as the acceptor. Owing to the reversible photoswitched interconversion of the two forms of the dithienylethene component, the fluorescence of the nanoparticles could be switched on/off by irradiation with UV or visible light, both in solution and in the solid state. As a result, the nanoparticles could be used as a photoerasable red‐luminescent ink and as a photocontrolled cell‐imaging agent. These functional nanoparticles can be expected to be useful in the fields of information security and biology. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbon with extended conjugation and broad absorption properties are interesting due to their easy accessibility, response to external stimuli and high stability. Herein, we report synthesis and full characterization of four compounds having multiple photoactive units in conjugation with a central pyrene group. The compound 2 with extended conjugation showed high fluorescence intensity in the solid state. Since the target molecules are non‐toxic and highly fluorescent, water dispersible nanoparticles were prepared from these molecules and explored for cellular imaging. [ABSTRACT FROM AUTHOR]

Herein, a facile, green and eco‐friendly approach has been applied for the synthesis of fluorescent green‐blue carbon dots (GB‐CDs) through the one‐pot hydrothermal treatment of Artocarpus lakoocha seeds for the first time and entirely characterized via a variety of instrumental techniques like fluorescent spectroscopy, Transmission Electron Microscopy (TEM), X‐Ray Photoelectron Spectra (XPS), X‐Ray diffraction (XRD) and Fourier Transform Infra‐red (FTIR) analysis. The as‐prepared GB‐CDs displayed high fluorescent quantum yield (QY) up to 38.5% and high photostability based on which GB‐CDs were successfully applied as a sensitive nanoprobe for the detection of Fe3+ ion. The sensing of Fe3+ shows a linear range from 2 to 6 μM and the limit of detection was found to be 0.62 μM. The sensing of Fe3+ was further investigated in the bona fide sample like river water and human blood serum. In addition, to explore the potential application, MTT assay was carried out on SH‐SY5Y neuroblastoma cells. The results showed negligible cytotoxicity as well as high cell viability, which revealed that GB‐CDs could be utilized as a fluorescent probe in living cells. [ABSTRACT FROM AUTHOR]

Manganese‐zinc ferrite nanoparticles were synthesized by using a hydrothermal treatment, coated with silica, and then tested as efficient cellular labels for cell tracking, using magnetic resonance imaging (MRI) in vivo. A toxicity study was performed on rat mesenchymal stem cells and C6 glioblastoma cells. Adverse effects on viability and cell proliferation were observed at the highest concentration (0.55 mM) only; cell viability was not compromised at lower concentrations. Nanoparticle internalization was confirmed by transmission electron microscopy. The particles were found in membranous vesicles inside the cytoplasm. Although the metal content (0.42 pg Fe/cell) was lower compared to commercially available iron oxide nanoparticles, labeled cells reached a comparable relaxation rate R2, owing to higher nanoparticle relaxivity. Cells from transgenic luciferase‐positive rats were used for in vivo experiments. Labeled cells were transplanted into the muscles of non‐bioluminescent rats and visualized by MRI. The cells produced a distinct hypointense signal in T2‐ or T2*‐weighted MR images in vivo. Cell viability in vivo was verified by bioluminescence. Track and trace: Nanoparticles with manganese‐zinc ferrite cores coated with silica are synthetized, characterized, and used as cell labels for cell tracking using magnetic resonance imaging (MRI). Particles enabled noninvasive visualization of transplanted labeled cells in vivo using MRI; their viability was verified by bioluminescence. [ABSTRACT FROM AUTHOR]

Abstract: Diketopyrrolopyrroles (DPPs) have recently attracted much interest as very bright and photostable red‐emitting molecules. However, their tendency to form nonfluorescent aggregates in water through the aggregation‐caused quenching (ACQ) effect is a major issue that limits their application under the microscope. Herein, two DPP molecules have been incorporated into the membrane of highly stable and water‐soluble quatsomes (QS; nanovesicles composed of surfactants and sterols), which allow their nanostructuration in water and, at the same time, limits the ACQ effect. The obtained fluorescent organic nanoparticles showed superior structural homogeneity, along with long‐term colloidal and optical stability. A thorough one‐ (1P) and two‐photon (2P) fluorescence characterization revealed the promising photophysical features of these fluorescent nanovesicles, which showed a high 1P and 2P brightness. Finally, the fluorescent QSs were used for the in vitro bioimaging of Saos‐2 osteosarcoma cell lines; this demonstrates their potential as nanomaterials for bioimaging applications. [ABSTRACT FROM AUTHOR]

The imaging of real-time fluxes of K+ ions in live cell with high dynamic range (5-150 × 10-3 m) is of paramount importance for neuroscience and physiology of the gastrointestinal tract, kidney, and other tissues. In particular, the research on high-performance deep-red fluorescent nanoparticle-based biosensors is highly anticipated. It is found that boron-dipyrromethene (BODIPY)- based K+-sensitive fluoroionophore FI3 encapsulated in cationic polymer RL100 nanoparticles displays unusually strong efficiency in staining of broad spectrum of cell models, such as primary neurons and intestinal organoids. Using comparison of brightness, photostability, and fluorescence lifetime imaging microscopy, it is confirmed that FI3 nanoparticles display distinctively superior intracellular staining compared to the free dye. FI3 nanoparticles in real-time live cell imaging are evaluated and it is found highly useful for monitoring intra- and extracellular K+ dynamics in cultured neurons. Proof-ofconcept in vivo brain imaging confirms applicability of the biosensor for visualization of epileptic seizures. Collectively, these data make fluoroionophore FI3 a versatile cross-platform fluorescent biosensor, broadly compatible with diverse experimental models, and crown-ether-based polymer nanoparticles can provide a new venue for the design of efficient fluorescent probes. [ABSTRACT FROM AUTHOR]

Abstract: Multifunctional materials with cell imaging and therapeutic functions are anticipated to provide promising agents in cancer treatment. Herein, folic acid modified conjugated polymer nanoparticles (FA‐CPNs) are exploited to target cancer cells and destroy the neighboring cancer cells. Folic acid in FA‐CPNs enables the strong binding with high affinity to folate receptor, a cancer‐cell‐associated protein, to target cancer cells. FA‐CPNs are able to produce cytotoxic reactive oxygen species upon irradiation 600 nm light, and therefore cause the cell death of folate receptor‐overexpressed cancer cells effectively. Therefore, the conjugated polymer‐based nanoparticles provide a multifunctional system for targeting cancer cells and photodynamic therapy. [ABSTRACT FROM AUTHOR]

Upconversion NaLuF4 nanophosphors (UCNPs), with excellent upconversion luminescence (UCL) and good biocompatibility, have been synthesized by the solvothermal method. The surfaces of the NaLuF4 UCNPs have been modified with the tripeptide arginylglycylaspartic acid (RGD) for targeting tumor cells, based on their high and specific affinity to the transmembrane receptor αvβ3 integrin. The morphology, size, and UCL properties of the UCNPs have been investigated in detail. The methyl thiazolyl tetrazolium assay suggests low cytotoxicity of the UCNPs to tumor cells and normal cells, indicative of their suitability for bioapplications. The RGD-modified NaLuF4 nanocrystals have been used for UCL-targeted cell imaging in U87MG tumor cells. The results demonstrate that RGD modification yields NaLuF4 UCNPs suitable for UCL-targeted cell imaging under excitation at 980 nm, owing to the high and specific affinity between RGD and αvβ3 integrin. [ABSTRACT FROM AUTHOR]

Biocompatible fluorescent polymeric nanoparticles (FPNs) are promising luminescent probes in cellular bioimaging, while the fabrication of high-quantum-yield FPN using nonconjugated heterochain polymers derived from step-growth polymerization is still in its infancy. Herein, the nonconjugated polyarylene ether nitrile (PEN) is endowed with aggregation-induced emission (AIE) feature by incorporation of an AIEgen named of 1,2-di(4-hydroxyphenyl)-1,2-diphenylethene into macromolecular backbone. Furthermore, the AIE-active PEN is crosslinked into water soluble fluorescent nanospheres showing good biocompatibility and strong emission ≈480 nm with a quantum yield of 21% in the presence of Ca2+, which allows the successful bioimaging of cancer cells. Due to the facile fabrication of FPNs and their effective bioimaging performance, the current work will open the way for the biomedical applications of various high performance polyarylene ethers. [ABSTRACT FROM AUTHOR]

Fluorescence photoswitching using nanomaterials has recently emerged as a promising approach for the imaging of biological targets. However, despite intensive research efforts during the last decade, practical microscopy of biological targets using photoswitchable nanoparticles in real time remains challenging. To address this problem, we have developed live macrophage cell imaging and single particle imaging methods, using photoswitchable fluorescent diarylethene-doped polymer nanoparticles (P-dots) under Xe lamp irradiation. We established a 34-times prolonged 'off-state', using P-dots doped with a diarylethene-containing methoxy substituent, upon visible-light irradiation using a Xe lamp and a green fluorescent protein filter cube. To demonstrate the practicality of doped P-dots imaging, we imaged lysosomes in macrophage cells, and observed 11-times slower recovery of the fluorescence from the 'off-state' to the 'on-state', indicating their potential for cellular imaging. [ABSTRACT FROM AUTHOR]

A simple and mild light-triggered fluorescent labeling approach, based on the photolysis and reactive carbene insertion of diazirine, to rapidly generate fluorescent nanoparticles is reported. Proof of concept studies demonstrated that the non-fluorescent SiNPs could be covalently labeled by diazirine-conjugated fluorescein (dFITC) upon photo irradiation ( λ=365 nm) to afford fluorescent SiNPs with good fluorescent stability and low cytotoxicity. In vitro cellular imaging results indicated that the internalization of SiNPs into living cells could be readily visualized based on fluorescein-labeled SiNPs (F-SiNPs) in real time. We believe that the light-triggered labeling approach may offer a valuable method for surface modification of nanomaterials to achieve new functions. [ABSTRACT FROM AUTHOR]

Luminescent silicon nanoparticles have recently attracted attention due to their remarkable stability, covalent functionalisation and tunable photoemission properties. Owing to their biocompatibility, low toxicity, and the small particle size that can be achieved by different synthetic approaches, these nanomaterials are candidates as cellular probes in the field of bioimaging, and potentially for in vivo applications. Tailoring the surface of the particles with active biomolecules such as sugar moieties can be an interesting strategy to increase the kinetics of internalisation or to vary the localisation of nanosystems in living cells. In this study, we synthesised and modified ultrasmall silicon nanoparticles with glucose covalently linked on their surface. Moreover, by varying the ratio between the amount of silicon nanoparticles and the saccharide groups, the amount of glucose, as a capping moiety, can be well controlled. FTIR spectroscopy, NMR spectroscopy, zeta potential measurements and anisotropy decay analysis confirmed the covalent binding of glucose to the nanoparticles. The photophysical behaviour of the surface-functionalised silicon quantum dots was not significantly different to that of the unmodified nanoparticles. In vitro studies demonstrated faster internalisation of the glucose-functionalised nanoparticles into HeLa cells. Different localisation and uptake kinetics of the glucose-modified particles compared to the unmodified particles are discussed in order to reveal the role played by the sugar molecules. [ABSTRACT FROM AUTHOR]

Enzyme, In Vivo, Lipid Nanoparticles, MiRNA Imaging, Signal Amplification Back Cover: An Enzymatically Gated Catalytic Hairpin Assembly Delivered by Lipid Nanoparticles for the Tumor-Specific Activation of Signal Amplification in miRNA Imaging (Angew. Keywords: Enzyme; In Vivo; Lipid Nanoparticles; MiRNA Imaging; Signal Amplification EN Enzyme In Vivo Lipid Nanoparticles MiRNA Imaging Signal Amplification 1 1 1 12/14/22 20221219 NES 221219 B Tumor-specific miRNA imaging b is achieved through the integration of enzyme-triggered catalytic hairpin assembly with lipid-nanoparticle-based delivery. [Extracted from the article]

Noble metal clusters is an emerging class of fluorescent probes, avoiding most of the drawbacks of common fluorescent compounds, and they are simple to prepare and have good water solubility, good biocompatibility and excellent fluorescence properties. In this study, we have explored the synthesis of the cytidine mediated gold-silver nanoclusters (AuAg NCs) and applied it for both in vitro cellular imaging and tumor in vivo detection. Experimental results show that the as-prepared AuAg NCs can be used as a sensitive fluorescent probe for cancer cells/tissue detection. Especially, it is evident that under the relevant light irradiation with the wavelength of 488 nm, obviously bright fluorescence signal could be readily detected from focus location of inoculating tumor mouse, implying its possible application for the effective in vivo tumor bioimaging. [ABSTRACT FROM AUTHOR]

In this study, we present a new application of the transmission electron microscopy dark field mode for cell imaging. We have applied this imaging mode to two types of cellular systems: human HeLa cells to analyze molecular membrane systems and HC11 mouse mammary cells containing lipid molecule droplets. We have also studied a third macromolecular system, copolymer nanoparticles for the characterization of core-shell structures. We want to show the effective use of diffraction contrast, even on amorphous systems for increasing the image contrast and the signal/noise ratio. We discuss the TEM dark field advantages for the analysis of polymers and other macromolecular systems, including biological, systems compared to the bright field mode. [ABSTRACT FROM AUTHOR]

A benign, clonable tag for the localization of proteins by electron microscopy of cells would be valuable, especially if it provided labelling with high signal-to-noise ratio and good spatial resolution. Here we explore the use of metallothionein as such a localization marker. We have achieved good success with desmin labelled in vitro and with a component of the yeast spindle pole body labelled in cells. Heavy metals added after fixation and embedding or during the process of freeze-substitution fixation provide readily visible signals with no concern that the heavy atoms are affecting the behaviour of the protein in its physiological environment. However, our methods did not work with protein components of the nuclear pore complex, suggesting that this approach is not yet universally applicable. We provide a full description of our optimal labelling conditions and other conditions tried, hoping that our work will allow others to label their own proteins of interest and/or improve on the methods we have defined. [ABSTRACT FROM AUTHOR]

This report describes the development of a facile method for the synthesis of cross-linked proteins with gold nanoclusters (CP-GNC). The synthesis reaction is completed within 15 min at 97 °C. The synthesized CP-GNC are characterized by using UV-vis absorption, fluorescence, X-ray photoelectron spectroscopy, and transmission electron microscopy. CP-GNC are approximately 100 nm in diameter and 700 nm in length, whereas AuNCs within the nanorods are approximately 6 nm in size. These materials are highly fluorescent with quantum yield of 7.2% and can be absorbed onto and release from bacterial cells in a pH-dependent and reversible manner. The recent data show that CP-GNC can be a useful, new tool with potential applications in fluorescent cell imaging and antibiotic targeting. [ABSTRACT FROM AUTHOR]

Lanthanide-doped upconversion nanoparticles (UCNPs) have shown great promise in versatile bioapplications. For the first time, organosilica-shelled β-NaLuF4:Gd/Yb/Er nanoprobes with a rattle structure have been designed for dual-modal imaging and photodynamic therapy (PDT). Benefiting from the unique rattle structure and aromatic framework, these nanoprobes are endowed with a high loading capacity and the disaggregation effect of photosensitizers. After loading of β-carboxyphthalocyanine zinc or rose Bengal into the nanoprobes, we achieved higher energy transfer efficiency from UCNPs to photosensitizers as compared to those with conventional core-shell structure or with pure-silica shell, which facilitates a large production of singlet oxygen and thus an enhanced PDT efficacy. We demonstrated the use of these nanoprobes in proof-of-concept X-ray computed tomography (CT) and UC imaging, thus revealing the great potential of this multifunctional material as an excellent nanoplatform for cancer theranostics. [ABSTRACT FROM AUTHOR]

Aggregation-induced emission (AIE) dye-based fluorescent glycopolymers nanoparticles (FGNs) are synthesized with abundant carbohydrate groups on the surface for the first time. This is carried out firstly by free radical polymerization between AIE monomer (PhE) and a renewable biobased monomer itaconic anhydride (ITA), then by the ring-opening reaction between ITA and glucosamine hydrochloride, to obtain glycopolymers with plenty of glycosyl groups on them. The resulted amphiphilic glycopolymer is prone to self-assemble into nanoparticles with high water dispersibility due to the surplus carboxyl groups and glycosyl groups covered on the surface, which can also be further functionalized. The obtained nanoparticles demonstrate strong fluorescence emission, owning to the AIE dyes in the core of nanoparticles. Biocompatibility evaluation and cell uptake behavior of the nanoparticles are further investigated to explore their potential biomedical applications; the demonstrated excellent biocompatibility makes them promising for cell imaging. [ABSTRACT FROM AUTHOR]

Persistent luminescence nanoparticles (PLNPs) hold great promise for the detection and imaging of biomolecules. Herein, we have demonstrated a novel nanoprobe, based on the manganese dioxide (MnO2)-modified PLNPs, that can detect and image glutathione in living cells and in vivo. The persistent luminescence of the PLNPs can be efficiently quenched by the MnO2 nanosheets. In the presence of glutathione (GSH), MnO2 was reduced to Mn2+ and the luminescence of PLNPs can be restored. The persistent luminescence property can allow detection and imaging without external excitation and avoid the background noise originating from the in situ excitation. This strategy can offer a promising platform for detection and imaging of reactive species in living cells or in vivo. [ABSTRACT FROM AUTHOR]

Aggregation-induced emission (AIE) dye-based cross-linked fluorescent polymeric nanoparticles (FPNs) are facilely prepared via a two-step polymerization process including emulsion polymerization and subsequent anhydride cross-linking. Then, a variety of characterization methods are carried out to determine the performance of the FPNs, which show high dispersibility and strong fluorescence in an aqueous solution due to the hydrophilic carboxyl groups on the surfaces and the AIE components as the cores. Biocompatibility evaluation and cell imaging results suggest that these FPNs are biocompatible for cell imaging. More importantly, this cross-linking strategy is proven to overcome the issue of critical micelle concentration and opens the opportunity to develop more robust fluorescent bioprobes. [ABSTRACT FROM AUTHOR]

Confocal Raman microscopy, a noninvasive, label-free, and high-spatial resolution imaging technique, in combination with K-mean cluster analysis and a correlation coefficient map, was employed to trace titanium dioxide (TiO2) nanoparticles in living MCF-7 and TERT cells. The penetration of TiO2 nanoparticles into cells revealed a gradual time-dependent diffusion of nanoparticles over the entire cell. Cell apoptosis was monitored by tracing cytochrome c diffusion into the cytoplasm. A comparison with the mitochondrial clustering indicated that cytochrome c was inside the mitochondria for TiO2 concentration of 2 µg ml−1. This result demonstrates that the presence of TiO2 particles within a cell does not induce apoptosis. We demonstrated that confocal Raman microscopy allow to follow penetration of TiO2 particles in cell and to monitor the apoptotic status of the penetrated cells. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Four new fluorescent dyes containing tetrahydro[5]helicene moiety characterized by three-primary emission colors (blue-green-red) are designed and synthesized, and their structures are characterized by NMR, MS, and single crystal X-ray crystallography. Organic nanoparticles based on the fluorescent dyes are then prepared by re-precipitation method, and their photophysical properties are investigated. These nanoparticles retain the strong emissions of the organic dyes, and multicolor nanoparticles were also prepared by simply tuning the ratios of the three-primary colors dyes. These organic nanoparticles exhibit low cytotoxicity, good photostability, and high quantum yields. Moreover, the nanoparticles can also be applied in the cell fluorescence imaging. Especially, it is interestingly found that the stained regions of these nanoparticles from membrane to cytoplasm for HeLa cells show obvious structure-dependent properties. This strategy provides a new perspective to fluorescence probe by molecular design for specific location imaging of living cells. [ABSTRACT FROM AUTHOR]

Red fluorescent organic nanopaticles (FONs) based on a diarylacrylonitrile derivative conjugated molecule were facilely prepared by surfactant modification. Such red FONs showed excellent water solubility and biocompatibility, making them promising for cell imaging applications. [ABSTRACT FROM AUTHOR]

Multicolor upconversion (UC) luminescence of NaYF4:Yb3+/Er3+ nanoparticles (NPs) was successfully tuned by simply controlling the NaF dosage. Unlike UC nanocrystals previously reported in the literature with multicolor emission obtained by varying the rare-earth dopants, the current work developed a new approach to tune the UC emission color by controlling the NaF concentration without changing the ratio and dosage of rare-earth ions. TEM and powder XRD were used to characterize the shape, size, and composition of the UC luminescent nanocrystals. The luminescence images, emission spectra, and multicolor emission mechanism of the NPs have also been demonstrated. As a result of the excellent ability of this new method to manipulate color emission, this will open up new avenues in the areas of bioprobes, light-emitting devices, color displays, lasers, and so forth. To demonstrate their biological applications, the water-stable, biocompatible, and bioconjugatable NaYF4:Yb3+/Er3+@poly(acrylic acid) NPs were synthesized by this developed strategy and applied in targeted-cell UC luminescence imaging. [ABSTRACT FROM AUTHOR]

This paper demonstrates the development of pH and thermo-responsive fluorescent nanoparticles, which are composed of graphene oxide (GO) with BODIPY conjugated PEG, to trigger the detection of cancer cells through imaging based on intracellular accommodation. Responsiveness to pH is studied using atomic force microscopy and apparent thickness differences are seen with changes in pH. Confocal images of the nanoparticles (NPs) exhibit remarkably bright fluorescence at lysosomal pH, while no fluorescence is observed under a physiological environment, making the NPs a novel fluorescent probe. The NPs are able to accumulate the hydrophobic anticancer drug DOX due to the hydrophobic surface of GO and show excellent drug release behavior. Therefore, the NPs developed are novel candidates for a fluorescent probe to identify cancer cells and a drug carrier for cancer therapy. [ABSTRACT FROM AUTHOR]

Chitosan with tetraphenylethene pendants (TPE-CS) are synthesized by reaction between amine and isothiocyanate groups of chitosan and tetraphenylethene (TPE), respectively. Nanoparticles of TPE-CS (TPE-CS NPs) are fabricated by ionic gelation method. The NPs are uniform in size, spherical in shape, monodispersed, and positive in surface charge. The suspension of TPE-CS NPs emits strong blue fluorescence under photoexcitation due to the aggregation-induced emission characteristics of the TPE moieties. The NPs can be internalized into cytoplasm through endocytosis pathway and retain inside the live cells to image the cells. Cytotoxicity assay reveals that TPE-CS NPs are cytocompatible and thus can be used for long-term live cell imaging. [ABSTRACT FROM AUTHOR]

Small (2-28 nm) NaREF4 (rare earth (RE)=Nd-Lu, Y) nanoparticles (NPs) were prepared by an oil/water two-phase approach. Meanwhile, hydrophilic NPs can be obtained through a successful phase-transition process by introducing the amphiphilic surfactant sodium dodecylsulfate (SDS) into the same reaction system. Hollow-structured NaREF4 (RE=Y, Yb, Lu) NPs can be fabricated in situ by electron-beam lithography on solid NPs. The MTT assay indicates that these hydrophilic NPs with hollow structures exhibit good biocompatibility. The as-prepared hollow-structured NPs can be used as anti-cancer drug carriers for drug storage/release investigations. Doxorubicin hydrochloride (DOX) was taken as model drug. The release of DOX from hollow α-NaLuF4:20 % Yb3+, 2 % Er3+ exhibits a pH-sensitive release patterns. Confocal microscopy observations indicate that the NPs can be taken up by HeLa cells and show obvious anti-cancer efficacy. Furthermore, α-NaLuF4:20 % Yb3+, 2 % Er3+ NPs show bright-red emission under IR excitation, making both the excitation and emission light fall within the 'optical window' of biological tissues. The application of α-NaLuF4:20 % Yb3+, 2 % Er3+ in the luminescence imaging of cells was also investigated, which shows a bright-red emission without background noise. [ABSTRACT FROM AUTHOR]

Intracellular detection is highly desirable for biological research and clinical diagnosis, yet its quantitative analysis with noninvasivity, sensitivity, and accuracy remains challenging. Herein, a near‐infrared (NIR) dual‐excitation strategy is reported for ratiometric intracellular detection through the design of dye‐sensitized upconversion probes and employment of a purpose‐built NIR dual‐laser confocal microscope. NIR dye IR808, a recognizer of intracellular analyte hypochlorite, is introduced as energy donor and Yb,Er‐doped NaGdF4 upconversion nanoparticles are adopted as energy acceptor in the as‐designed nanoprobes. The efficient analyte‐dependent energy transfer and low background luminescence endow the nanoprobes with ultrahigh sensitivity. In addition, with the nonanalyte‐dependent upconversion luminescence (UCL) excited by 980 nm as a self‐calibrated signal, the interference from environmental fluctuation can be alleviated. Furthermore, the dual 808/980 nm excited ratiometric UCL is demonstrated for the quantification of the level of intracellular hypochlorite. Particularly, the intrinsic hypochlorite with only nanomolar concentration in live MCF‐7 cells in the absence of exogenous stimuli is determined. Such an NIR dual‐excitation ratiometric strategy based on dye‐sensitized UCL probes can be easily extended to detect various intracellular analytes through tailoring the reactive NIR dyes, which provides a promising tool for probing biochemical processes in live cells and diagnosing diseases. [ABSTRACT FROM AUTHOR]