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Comprehensive Summary: Autophagy is a multi‐step cell metabolism process in which cells remove damaged and unwanted materials. During autophagy, autophagosomes fuse with lysosomes to form autophagosomes. Autophagosomal membrane components are recycled from autolysosomes through the autophagosomal components recycling (ACR), while lysosomal components circulate on the autolysosomal surface through the autophagic lysosome reformation (ALR) process. Autolysosomes contain components from autophagosomes and lysosomes. However, whether there is a fusion between autolysosome and autophagosome or lysosome at the organelle level remains unknown. In this study, a pH and viscosity dual‐controlled mitochondria‐targeting fluorescent probe Mito‐Q was designed based on an asymmetric norcyanine to achieve the high‐contrast imaging of mitochondria‐containing autolysosomes. Mito‐Q not only effectively detected mitochondrial viscosity changes and mitophagy with high sensitivity, but more importantly, the fusion of mitochondria‐containing autolysosomes and autophagosomes (FMAA) was observed during autophagy by the real‐time confocal imaging of HeLa cells. [ABSTRACT FROM AUTHOR]

Photoactivatable fluorophores are useful tools in live cell imaging due to precise spatial and temporal control. Herein, a tandem visible‐light photodecaging and tautomerization strategy is proposed as an activation mechanism for the construction of photoconvertible boron dipyrromethenes (BODIPY) dyes, from which nitro‐benzyloxy BODIPY derivatives are developed as a new class of visible light photoactivated fluorophores. Upon exposure to visible light, the nitro‐benzyloxy moiety is released and the BODIPY moiety is converted to the keto‐form BODIPY analog by tautomerization. The photoconversion process not only achieves over 50 nm blue shift of absorption/emission maxima but also provides bright fluorescence for both the pre‐ and post‐activation forms. Mechanism studies indicate that no indications of radical species and singlet oxygen are involved in this unique photoconversion and both UV and visible light irradiation can efficiently activate this photoinduced release of the nitrobenzyl alcohol through photoexciting of BODIPY core rather than classical nitro‐benzyloxy photocage. Cell and vesicle imaging is successfully performed using the new photoconversion dyes. The results show that these new photoconvertible dyes are highly efficient, universal, and non‐cytotoxic, which are valuable for the development of promising photoactivated molecules. [ABSTRACT FROM AUTHOR]

Phosphorescent probes often show sensitive response toward analytes at a specific wavelength. However, oxygen quenching usually occurs at the same wavelength and thus hinders the accurate detection of analytes. In this study, we have developed dual‐emissive iridium(III) complexes that exhibit phosphorescence responses to copper(II) ions at a wavelength distinct from that where oxygen quenching occurs. The complexes displayed colorimetric phosphorescence response in aqueous solutions under different copper(II) and oxygen conditions. In cellular imaging, variation in oxygen concentration over a large range from 5 % to 80 % can modulate the intensity and lifetime of green phosphorescence without affecting the response of red phosphorescence toward intracellular copper(II) ions. [ABSTRACT FROM AUTHOR]

Phosphorescent probes often show sensitive response toward analytes at a specific wavelength. However, oxygen quenching usually occurs at the same wavelength and thus hinders the accurate detection of analytes. In this study, we have developed dual‐emissive iridium(III) complexes that exhibit phosphorescence responses to copper(II) ions at a wavelength distinct from that where oxygen quenching occurs. The complexes displayed colorimetric phosphorescence response in aqueous solutions under different copper(II) and oxygen conditions. In cellular imaging, variation in oxygen concentration over a large range from 5 % to 80 % can modulate the intensity and lifetime of green phosphorescence without affecting the response of red phosphorescence toward intracellular copper(II) ions. [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]

A library of eight different cationic emitters with emission properties in solution and in solid‐state (solution and solid‐state emitters – SSSE) is presented. These compounds, bearing either ammonium or pyridinium groups, have been investigated regarding their photophysical properties as well as their potential application in biological imaging. Besides high quantum yields as well as a high degree of stability during the imaging process, it was additionally revealed that a broad range of biological targets can be addressed, such as different bacterial strains, human cells as well as protists. The reported SSSE approach employing the mentioned robust emitters for biological imaging, will contribute to a rapid and facile way to design and apply affordable emitters with outstanding properties. Additionally, these emitters will overcome the drawbacks of classical luminophores and agents featuring well‐known aggregation‐induced emission (AIE) or aggregation‐caused quenching (ACQ) properties. [ABSTRACT FROM AUTHOR]

Dual‐state emission luminogens (DSEgens) are receiving research interest in the construction of multifunctional materials due to their inherent advantage of high emission efficiency in both the molecularly dispersed solution state and the solid state. However, it remains challenging in synthesizing DSEgens via a delicate manipulation of the molecular structures. This work presents an example of bright DSEgen synthesis by tuning the molecular electronic structures and conformations. Three coumarin‐tetraphenylethylene (TPE) molecules with a donor‐acceptor electronic structure and highly twisting conformations have been synthesized. While compound resulting from direct conjugation of coumarin with a TPE unit shows aggregation‐induced emission, compound with an N,N‐diaminoethyl modification on the 7‐position of coumarin and compound with a further phenyl linker between coumarin and TPE units feature strong dual‐state emission. Benefiting from their strong solid emission and twisting conformations, these fluorophores display reversible mechanofluorochromism. Finally, applications for rewritable information storage in the solid state and live‐cell imaging in the solution state were demonstrated. [ABSTRACT FROM AUTHOR]

Fluorescent probes are attractive in diagnosis and sensing. However, most reported fluorophores can only detect one or few analytes/parameters, notably limiting their applications. Here we have designed three phenanthridine‐based fluorophores (i.e. B1, F1, and T1 with 1D, 2D, and 3D molecular configuration, respectively) capable of monitoring various microenvironments. In rigidifying media, all fluorophores show bathochromic emissions but with different wavelength and intensity changes. Under compression, F1 shows a bathochromic emission of over 163 nm, which results in organic fluorophore‐based full‐color piezochromism. Moreover, both B1 and F1 exhibit an aggregation‐caused quenching (ACQ) behavior, while T1 is an aggregation‐induced emission (AIE) fluorophore. Further, F1 and T1 selectively concentrate in cell nucleus, whereas B1 mainly stains the cytoplasm in live cell imaging. This work provides a general design strategy of versatile fluorophores for microenvironmental monitoring. [ABSTRACT FROM AUTHOR]

Fluorescent probes are attractive in diagnosis and sensing. However, most reported fluorophores can only detect one or few analytes/parameters, notably limiting their applications. Here we have designed three phenanthridine‐based fluorophores (i.e. B1, F1, and T1 with 1D, 2D, and 3D molecular configuration, respectively) capable of monitoring various microenvironments. In rigidifying media, all fluorophores show bathochromic emissions but with different wavelength and intensity changes. Under compression, F1 shows a bathochromic emission of over 163 nm, which results in organic fluorophore‐based full‐color piezochromism. Moreover, both B1 and F1 exhibit an aggregation‐caused quenching (ACQ) behavior, while T1 is an aggregation‐induced emission (AIE) fluorophore. Further, F1 and T1 selectively concentrate in cell nucleus, whereas B1 mainly stains the cytoplasm in live cell imaging. This work provides a general design strategy of versatile fluorophores for microenvironmental monitoring. [ABSTRACT FROM AUTHOR]

In this work, the nitrogen doped carbon quantum dots (N‐CQDs) were synthesized by a simple microwave hydrothermal method using citric acid (carbon source) and urea (dopant) and optimized the preparation conditions by orthogonal tests. The synthesized N‐CQDs emitted a bright blue fluorescence with specific selectivity for Hg2+. The study revealed a static quenching mechanism of Hg2+ on the N‐CQDs. The N‐CQDs showed good linear correlation in the range of 0–120 μM for the detection of Hg2+ with a low detection limit of 22.50 nM. We also demonstrated the suitability of the N‐CQDs for the detection of Hg2+ in tap water and industrial wastewater with spiked recoveries of 97.56 %–103.58 %. In addition, the synthesized N‐CQDs with high fluorescence intensity, good optical stability and biocompatibility were successfully applied to fluorescent inks and imaging of Hela cells. This indicated that the synthesized N‐CQDs have promising applications in Hg2+ detection, bioimaging, and fluorescence anti‐counterfeiting. [ABSTRACT FROM AUTHOR]

Real‐time optical imaging of immune cells can contribute to understanding their pathophysiological roles, which still remains challenging. Current sensitive chemiluminophores have issues of short half‐lives and low brightness, limiting their ability for in vivo longitudinal monitoring of immunological processes. To tackle these issues, we report benzoazole‐phenoxyl‐dioxetane (BAPD)‐based chemiluminophores with intramolecular hydrogen bonding for in vivo imaging of neutrophils. Compared with the classical counterpart, chemiluminescence half‐lives and brightness of BAPDs in the aqueous solution are increased by ∼ 33‐ and 8.2‐fold, respectively. Based on the BAPD scaffold, a neutrophil elastase‐responsive chemiluminescent probe is developed for real‐time imaging of neutrophils in peritonitis and psoriasis mouse models. Our study provides an intramolecular hydrogen bonding molecular design for improving the performance of chemiluminophores in advanced imaging applications. [ABSTRACT FROM AUTHOR]

Real‐time optical imaging of immune cells can contribute to understanding their pathophysiological roles, which still remains challenging. Current sensitive chemiluminophores have issues of short half‐lives and low brightness, limiting their ability for in vivo longitudinal monitoring of immunological processes. To tackle these issues, we report benzoazole‐phenoxyl‐dioxetane (BAPD)‐based chemiluminophores with intramolecular hydrogen bonding for in vivo imaging of neutrophils. Compared with the classical counterpart, chemiluminescence half‐lives and brightness of BAPDs in the aqueous solution are increased by ∼ 33‐ and 8.2‐fold, respectively. Based on the BAPD scaffold, a neutrophil elastase‐responsive chemiluminescent probe is developed for real‐time imaging of neutrophils in peritonitis and psoriasis mouse models. Our study provides an intramolecular hydrogen bonding molecular design for improving the performance of chemiluminophores in advanced imaging applications. [ABSTRACT FROM AUTHOR]

Fluorescent probes provide essential tools for studying biological systems. For the prolonged imaging of cellular analytes, the fast clearance of small-molecular probes and products is a matter of concern in the quantitative analysis. Activatable probes that produce insoluble products inside cells can be used for prolonged imaging, but those with ratiometric imaging capability are rare. We disclose a novel sensing platform that is capable of prolonged imaging, in addition to ratiometric signaling for reliable quantitative analysis. Specifically, 3-(pyridin-4-yl)-8-(pyrrolidin-1-yl)-2Hbenzo[ g]chromen-2-one and its pyridinium salt as a product/ probe couple constitute the ratiometric sensing platform. As the former dye produces highly emissive insoluble nanoaggregates inside cells, a fluorescent probe in the latter form enables prolonged imaging of the target analyte in cells as well as in tissue by two-photon microscopy. [ABSTRACT FROM AUTHOR]

Bioinspired carbon dots (CDs) with excellent biocompatibility were prepared from egg white as precursors through a simple hydrothermal method at 200 °C for 4 hours. The obtained CDs exhibited bright blue fluorescence, excellent optical stability, and sensitive response to tetracycline. Under the optimized synthetic conditions, the fluorescence quantum yield is 17.6 %. The fluorescence intensity of CDs at 440 nm could be quenched linearly with the addition of tetracycline in the range of 0.1–200 μmol L−1 due to the internal filtering effect. The proposed detection platform has been applied in the determination of tetracycline in milk samples with good results. The limit of detection is 32.3 nmol L−1, and the spiked recoveries are in the range of 93–103 %. Additionally, the CDs could also be applied to cell imaging, implying good biocompatibility and low toxicity. As a type of green and effective multi‐functional fluorescence materials, the CDs have potential applications in biochemical sensing and biomedical imaging. [ABSTRACT FROM AUTHOR]

The current review describes advances in the use of fluorescent 2,1,3‐benzothiadiazole (BTD) derivatives after nearly one decade since the first description of bioimaging experiments using this class of fluorogenic dyes. The review describes the use of BTD‐containing fluorophores applied as, inter alia, bioprobes for imaging cell nuclei, mitochondria, lipid droplets, sensors, markers for proteins and related events, biological processes and activities, lysosomes, plasma membranes, multicellular models, and animals. A number of physicochemical and photophysical properties commonly observed for BTD fluorogenic structures are also described. [ABSTRACT FROM AUTHOR]

The synthesis, photophysical, and electrochemical properties of selectively mono‐, bis‐ and tris‐dimethylamino‐ and trimethylammonium‐substituted bis‐triarylborane bithiophene chromophores are presented along with the water solubility and singlet oxygen sensitizing efficiency of the cationic compounds Cat1+, Cat2+, Cat(i)2+, and Cat3+. Comparison with the mono‐triarylboranes reveals the large influence of the bridging unit on the properties of the bis‐triarylboranes, especially those of the cationic compounds. Based on these preliminary investigations, the interactions of Cat1+, Cat2+, Cat(i)2+, and Cat3+ with DNA, RNA, and DNApore were investigated in buffered solutions. The same compounds were investigated for their ability to enter and localize within organelles of human lung carcinoma (A549) and normal lung (WI38) cells showing that not only the number of charges but also their distribution over the chromophore influences interactions and staining properties. [ABSTRACT FROM AUTHOR]

Red fluorescent carbon dots (R‐CDs) are special desirable for biochemical analysis due to good biological compatibility and deep penetration; however, they remain as bottlenecks due to difficulties in expanding the sp2 domain, especially those are fused from rigid polycyclic conjugated molecules (RPCMs) with heteroatom substituents due to huge steric hindrance and heteroatom blockage toward graphic lattice. Here, an RPCM with heteroatom substituents, 1,5‐diamino‐4,8‐dihydroxyanthraquinone (DDAQ), based self‐doped R‐CDs with PL emission at 635 nm is reported. Further investigations reveal that the expanding, hybrid sp2 domain with indanthrone tannin structure from DDAQ is mainly responsible for the obtained red fluorescence of R‐CDs. Taking advantage of optical properties, R‐CDs are considered to construct a colorimetric/fluorescent dual mode sensing array for quantifying trace levels of Fe3+ and glyphosate based on the static quenching, and a biomarker for cell imaging. The CD‐based sensors exhibit outstanding recovery, high selectivity, and sensitivity, also facilitated dual‐mode detection with the naked‐eye. The R‐CDs have low cytotoxicity, good cell membrane penetration for rapid cell entry, and high resolution, demonstrating their potential for biolabeling and bioanalytic applications. [ABSTRACT FROM AUTHOR]

Cyclometalated iridium (Ir) complexes having Ir(tpy)3 (tpy=2- (4'-tolyl)pyridine) scaffold exhibit promising potential for the diagnosis of cancer, as phosphorescent probes for cellular imaging and in the treatment of cancer, due to their high stability, tunable photophysical properties, and biological activities. We previously reported on the synthesis of some cationic amphiphilic Ir(III) complex-peptide hybrids (IPHs) such as 2 and 3 that contain KK(K)GG peptide units (K: lysine, G: glycine) that are attached via alkyl chain (C2~C16) linkers and induce paraptosis-like cell death in Jurkat (T-lymphocyte leukemia) cancer cells through multiple cell death pathways. Herein, we report on the design and synthesis of two IPHs, 4 and 5, which possess two and one KKKGG sequences, respectively, and an examination of the effect of the number of peptide units on their anticancer activity. Our evaluations of the anticancer properties of 3-5 suggested that 3 and 4 are more cytotoxic than 5 against Jurkat cells, indicating a positive relationship between the number of H2N-KKKGG units in 3-5 and their anticancer activity. In addition, a parallel relationship was observed between the cytotoxicity of 3-5 and Ca2+ overload in mitochondria, suggesting the direct transfer of Ca2+ from the endoplasmic reticulum to mitochondria. [ABSTRACT FROM AUTHOR]

As one of the most important minerals in the body, potassium is vital for the heart and neurons. Methods that can non‐invasively and accurately monitor changes in potassium balances would benefit disease diagnoses as well as offer insight into pathologies. Among the sensing approaches, fluorescent probes serve as a unique detection method for its simplicity, tunable detection range, and bioimaging ability. The design of new probes with highly selective K+ receptors and transduction functionality remains a challenge that is motivated by numerous sensing and detection applications. In this minireview, fluoroionophores are summarized that undergo transduction, producing fluorescence signals when interacting with, e. g. potassium ions. The properties of ionophores (afford selective interaction with potassium) and fluorophores (generate signal read‐out) are discussed. Molecular structure design and sensing mechanisms are included along with cell imaging applications. The selectivity towards K+ and the absorption/emission characteristics of the probes are of particular interest. [ABSTRACT FROM AUTHOR]

The photoluminescence (PL) saturation of CdSe/ZnS core/shell inorganic semiconductor quantum dots (QDs) and its utility as a probe for saturated excitation (SAX) microscopy are reported. Under saturating excitation power densities, the PL signal was demodulated and recorded at harmonics of the fundamental frequency. For commercially available Qdot® 655 ITK™ QDs, the power density required to achieve saturation was dependent upon the local environment of the QDs. For QDs deposited and dried on a glass substrate, the excitation power density required for PL saturation was less than 1 kW/cm2. Compared to this, saturation of PL for QDs dispersed in water required an excitation power density greater than 200 kW/cm2. This observation is manifested as a limitation in the imaging of hydrated samples, as demonstrated for HeLa cells labelled with biotinylated‐phalloidin followed by labelling with streptavidin‐coated QDs. As saturation affects the obtained spatial resolution in several imaging formats, including confocal imaging, the provided data will aid in obtaining the optimal spatial resolution when using QD probes to image biological samples. [ABSTRACT FROM AUTHOR]

Functional polymer, especially the one based on renewable and sustainable materials, has attracted increasing attention to satisfy the growing demand for the design of stimuli‐responsive devices. Methylcellulose (MC) is a water‐soluble derivative of cellulose, which has been widely used in many fields for its biocompatibility and biological inertness. In this work, MC is labeled by tetraphenylethylene (TPE) via azide–alkyne click reaction to obtain a fluorescent cellulose‐based derivative of MC‐TPE. The degree of substitution of MC‐TPE is determined to be 0.074, which can be self‐assembled into micelles in water with the size of 42 ± 6 nm. MC‐TPE shows thermoresponsivity and thermoreversibility in size, transmittance, and fluorescence, enabling it to work as a fluorescent thermosensor. Moreover, MC‐TPE exhibits nontoxicity and biocompatibility, allowing its application in MCF‐7 cell imaging. Therefore, this newly functional natural polymer shows promising potentials in the fields of sensing and bioimaging. [ABSTRACT FROM AUTHOR]

Fluorescence imaging using poly(phenylene ethynylene) (PPE) based conjugated polyelectrolytes (CPEs) has garnered considerable attention in the recent past due to their remarkable photophysical properties. In this report, we studied the fluorescence imaging properties of a set of six PPE‐based CPEs appended with side chains varying in structure and number of cationic charges. The photophysical and aggregation features of the CPEs depend on the overall charge density on the polymer in water. The cytotoxicity of the CPEs was evaluated against MCF‐7 mammalian cells, which revealed that polyelectrolytes with less cationic charge are less cytotoxic and vice versa. Confocal laser scanning microscopy (CLSM) studies showed that all the CPEs could efficiently penetrate into the MCF‐7 cells after 10 h of incubation. The transit of CPEs into the lysosomes was confirmed by comparison with the uptake of LysoTracker Red DND‐99 dye, which also revealed that the polyelectrolytes are highly photostable. We also demonstrated that the imidazolium‐functionalized CPEs could selectively stain bacteria over mammalian cells, suggesting the importance of CPEs for clinical applications. [ABSTRACT FROM AUTHOR]

We have recently reported photocaged nanobodies, termed photobodies, that can be light‐activated in their antigen binding properties due to the removal of the photolabile protection group. We aimed to establish the delivery and activation of photobodies inside mammalian cells, because intracellular protein manipulation and detection by using antibodies and antibody fragments like nanobodies is highly attractive, however, the spatial and temporal control of their application in cells is extremely limited. AntiGFP photobodies with ortho‐nitrobenzyltyrosine in the paratope region were delivered into HeLa cells using the bead‐loading technique. Light‐activation was carried out with spatial control in single cells to trigger binding to a GFP tag fused to endogenously expressed target proteins. By means of its fused nuclear localization sequence, an activated photobody dragged the GFP fusion protein into the nucleus, the kinetics of which could be monitored using live cell microscopy. These results show the potential of photobodies for intracellular applications. [ABSTRACT FROM AUTHOR]

A new series of aza‐BODIPYs (CN−X) with significantly red‐shifted absorbances were designed and synthesized by installation of various electron‐donating groups on the para‐positions of 3,5‐phenyl groups while strong electron‐withdrawing groups (nitrile groups) were fixed on the para‐positions of 1,7‐phenyl moieties. Interestingly, strong electron‐donating groups such as N'N‐dimethylaniline (CN−NMe2) could provide strong NIR absorption up to 857 nm and weak fluorescence emission up to 967 nm, whereas strong evidence supported heat production via non‐radiative decay after excitation. Electrochemical studies revealed that the substituents on the dyes showed strong effects on the oxidation potentials where the oxidation wave of CN−NMe2 occurred at the lowest overpotential, followed by CN−OMe, CN−Me, CN−Br and CN−H, respectively. Calculations were also performed to understand the push‐pull effect of the substituents on the aza‐BODIPY systems. Finally, applications of dyes in NIR cancer cell imaging and the NIR‐II photothermal effect were also investigated. [ABSTRACT FROM AUTHOR]

Two structurally unique aggregation induced emission (AIE)‐active luminogens have been designed and synthesized based on the furocarbazole skeleton. Such small molecule AIEgens were designed based on forbidden planarity and engineering a twist into the scaffold to realize induction of emission in the aggregated states. The structures were fully characterized and their thermal stabilities, electronic properties, photophysical and electrochemical properties were systematically investigated. The unique twist in the molecules as evident from their X‐ray crystal structure along with the short intermolecular interactions enhances the structural rigidification and restricts detrimental π–π stacking interactions, restricting the internal rotations (RIR) accompanied by a curb of the ICT process, resulting in enhanced emission in the aggregated state. This intriguing luminescent property enabled one of the luminogens to selectively detect trinitrophenol (TNP) over other nitroaromatics in both aqueous and organic media at nanomolar concentrations. Moreover, the good photostabilities and biocompatibilities empowered both luminogens to function as fluorescent bioprobes for cancer cell imaging. [ABSTRACT FROM AUTHOR]

Synthetic strategies were developed for the preparation of indolo‐imine boron difluoride (IIBD) dyes based on indolo[3,2‐b]carbazole structures. Four new IIBD dyes were synthesized and were subsequently converted into the corresponding ‐BPh2/‐BOR2 and N‐t‐Boc/N‐benzoyl derivatives. The photophysical properties of all dyes were determined in both solution and solid media. All dyes absorb in the UV/Vis region, show negative solvatochromism, and are fluorescent in both media. The absorbance and fluorescence properties of the dyes can be tuned over a wide range by synthetic modifications. These findings are rationalized by theoretical calculations that correspond well to the experimental shifts, explain the negative solvatochromism, and allow quantification of charge transfer (CT). Similarly, the HOMO–LUMO energies measured by CV are in good agreement with the theoretically calculated values. Interestingly, the energy gaps of the dyes can also be tuned by structural modulations using the developed chemical route. Charge transport properties of the dyes were checked and showed that the N‐benzoyl derivative has the highest hole mobility which is useful for organic field effect transistor (OFET) applications. In addition, easy cellular uptake of the dyes, their low toxicity and high stability inside the cells associated with bright fluorescence in the cytoplasm will be useful for their future application as cellular imaging agents. All of these aspects highlight the interest of this new class of dyes. [ABSTRACT FROM AUTHOR]

Organic fluorophores are essential in microscopic imaging of biological systems. New fluorophores with distinct features are in demand for bioimaging. Herein we report new bent benzocoumarin dyes that are fluorescent both in solution and in the solid state. The latter property enables us to form fluorescent nanoparticles with a mean size of 120–157 nm or larger depending on conditions. Some of the new dyes provide bright fluorescent images in cell, with formation of particulate spots that persist even after several washout procedures, and, furthermore, in tissue under two‐photon excitation at 900 nm. Such dyes have potential for the development of fluorescent probes for enhanced cellular fluorescence. [ABSTRACT FROM AUTHOR]

Phytomedicines have been beneficial to humankind for the treatment of implacable ailments from time immemorial. In this report, we have synthesized a carbon dots as a photomedicine from traditional phytomedicine Andrographis paniculata which is widely spread across Southern and Southeastern Asia. Interestingly, these carbon dots exhibited unique pink fluorescence that is perceptibly distinctive from the previous reports. The inherent properties of carbon dots were characterised using Transmission Electron Microscopy, Fluorescence spectroscopy, Absorption spectroscopy, Fourier transform infrared spectroscopy, Selected area diffraction, X‐Ray Diffraction, and Energy Dispersive X‐ray Spectroscopy. Furthermore, thermal stability of carbon dots was determined using Thermo gravimetric analysis. The carbon dots are fabricated to possess breast cancer cell bioimaging applications apart from anti‐bacterial activities against clinically isolated strains of gram‐positive and gram‐negative bacteria and free radicals sensing and scavenging attributes. These findings establish carbon dots as a potential photomedicine with wide healthcare applications. [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]

In this study, we successfully synthesized CuxCoyS supraparticles (SPs) on the nanoscale featuring multiple pores inside and strong absorption from 400 to 900 nm. Porous CuxCoyS SPs produced the highest reactive oxygen species (ROS) yield (1.39) when illuminated with near‐infrared (NIR) light. Furthermore, we demonstrated that CuxCoyS SPs could be used to identify cancer cells through intracellular telomerase‐responsive fluorescence (FL) imaging in living cells. Because the CuxCoyS SPs were associated with telomerase‐responsive bioimaging and high ROS production, they can be efficiently used in the diagnosis and therapy of tumors with high selectivity and excellent therapeutic effects in vivo. This study provides a new vision for the creation of multifunctional SPs, which can be used as cellular sensors and control tools for pathologies across a broad range of biological systems. [ABSTRACT FROM AUTHOR]

A fluorescent, diselenide‐containing 9,10‐distyrylanthracene (DSA) derivative (SeDSA) with aggregation‐induced emission (AIE) characteristic was successfully synthesized and SeDSA nanoparticles (NPs) were prepared through a nanoprecipitation method. SeDSA could coassemble with an antitumor prodrug, diselenide‐containing paclitaxel (SePTX), which could be obtained by precipitation, to form SeDSA‐SePTX Co‐NPs (Co‐NPs). Molecular dynamics (MD) simulations reveal that the driving forces for the self‐assembly behaviors of SeDSA NPs and SePTX NPs are π–π interactions and hydrophobic interactions, respectively, while the driving forces for Co‐NPs include hydrophobic interactions between SeDSA and SePTX, π–π interactions between SeDSA molecules and hydrophobic interactions between SePTX molecules. Meanwhile, Se‐Se bonds play a crucial role in balancing the intramolecular forces. These diselenide‐containing nanoparticles (SeDSA NPs, SePTX NPs and Co‐NPs) exhibit a high stability under physiological conditions and excellent reduction‐sensitivity in the presence of the redox agent glutathione (GSH) because of the selenium‐sulfur exchange reaction between diselenide and GSH. Both SeDSA NPs and Co‐NPs show strong orange fluorescence emissions on the account of the AIE feature of SeDSA and they were easily internalized by HeLa and HepG2 cells. Distinctively, the Co‐NPs combine the advantage of SeDSA and SePTX for cell imaging and antineoplastic activity, and exhibit selectivity of cytotoxicities between neoplasia cells and normal cells. This study highlights the development of diselenide‐containing AIEgens as a unique approach to prepare uniform and stable fluorescent nanoparticles for the application in cell imaging and tumor treatment. [ABSTRACT FROM AUTHOR]

Metal nanoclusters (NCs) are considered ideal nanomaterials for biological applications owing to their strong photoluminescence (PL), excellent photostability, and good biocompatibility. This study presents a simple and versatile strategy to design proteins, via incorporation of a di‐histidine cluster coordination site, for the sustainable synthesis and stabilization of metal NCs with different metal composition. The resulting protein‐stabilized metal NCs (Prot‐NCs) of gold, silver, and copper are highly photoluminescent and photostable, have a long shelf life, and are stable under physiological conditions. The biocompatibility of the clusters was demonstrated in cell cultures in which Prot‐NCs showed efficient cell internalization without affecting cell viability or losing luminescence. Moreover, the approach is translatable to other proteins to obtain Prot‐NCs for various biomedical applications such as cell imaging or labeling. [ABSTRACT FROM AUTHOR]

Metal nanoclusters (NCs) are considered ideal nanomaterials for biological applications owing to their strong photoluminescence (PL), excellent photostability, and good biocompatibility. This study presents a simple and versatile strategy to design proteins, via incorporation of a di‐histidine cluster coordination site, for the sustainable synthesis and stabilization of metal NCs with different metal composition. The resulting protein‐stabilized metal NCs (Prot‐NCs) of gold, silver, and copper are highly photoluminescent and photostable, have a long shelf life, and are stable under physiological conditions. The biocompatibility of the clusters was demonstrated in cell cultures in which Prot‐NCs showed efficient cell internalization without affecting cell viability or losing luminescence. Moreover, the approach is translatable to other proteins to obtain Prot‐NCs for various biomedical applications such as cell imaging or labeling. [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]

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]

Bioimaging techniques that allow the visualization of ferrocene in living cells do not exist. This work addresses this challenging problem, and a new indirect approach for the bioimaging of ferrocenyl compounds in living and fixed cells is proposed. It is based on the structural similarity of metallocenyl (ferrocenyl and ruthenocenyl) groups to their metal-free [2.2]paracyclophanyl congeners. Three adequately designed compounds were obtained. They share a 5-(1-ethynylpyrenyl)uracil group as a common structural motif and differ in their three-dimensional aromatic substituents, namely, [2.2]paracyclophanyl, ferrocenyl and ruthenocenyl. The first substituent allows pyrenyl luminescence to occur, whereas the latter two act as quenchers. The accumulation of the luminescent derivative in the membranes, cytoplasm and mitochondria of living and fixed cells was confirmed by confocal microscopy. Microscopy studies were further correlated with high-resolution continuum-source atomic absorption spectroscopy (HR-CS AAS) measurements of the ruthenocenyl compound that confirmed the uptake of ruthenium into the cells. Thus, taking into account the overall similarity of the compounds under study, it can be hypothesized that the metallocenyl derivatives are localized in the membranes, cytoplasm and mitochondria of the assayed cells. This is the basis for the more general concept of the utilization of luminescent [2.2]paracyclophanes as probes in indirect bioimaging studies of metallocene derivatives. [ABSTRACT FROM AUTHOR]

Photolabile protecting groups (or "photocages") enable precise spatiotemporal control of chemical functionality and facilitate advanced biological experiments. Extant photocages exhibit a simple input-output relationship, however, where application of light elicits a photochemical reaction irrespective of the environment. Herein, we refine and extend the concept of photolabile groups, synthesizing the first Ca2+- sensitive photocage. This system functions as a chemical coincidence detector, releasing small molecules only in the presence of both light and elevated [Ca2+]. Caging a fluorophore with this ion-sensitive moiety yields an "ion integrator" that permanently marks cells undergoing high Ca2+ flux during an illumination-defined time period. Our general design concept demonstrates a new class of light-sensitive material for cellular imaging, sensing, and targeted molecular delivery. [ABSTRACT FROM AUTHOR]

Advanced tools for cell imaging are of great interest for the detection, localization, and quantification of molecular biomarkers of cancer or infection. We describe a novel photopolymerization method to coat quantum dots (QDs) with polymer shells, in particular, molecularly imprinted polymers (MIPs), by using the visible light emitted from QDs excited by UV light. Fluorescent core-shell particles specifically recognizing glucuronic acid (GlcA) or N-acetylneuraminic acid (NANA) were prepared. Simultaneous multiplexed labeling of human keratinocytes with green QDs conjugated with MIPGlcA and red QDs conjugated with MIP-NANA was demonstrated by fluorescence imaging. The specificity of binding was verified with a non-imprinted control polymer and by enzymatic cleavage of the terminal GlcA and NANA moieties. The coating strategy is potentially a generic method for the functionalization of QDs to address a much wider range of biocompatibility and biorecognition issues. [ABSTRACT FROM AUTHOR]

Advanced tools for cell imaging are of great interest for the detection, localization, and quantification of molecular biomarkers of cancer or infection. We describe a novel photopolymerization method to coat quantum dots (QDs) with polymer shells, in particular, molecularly imprinted polymers (MIPs), by using the visible light emitted from QDs excited by UV light. Fluorescent core-shell particles specifically recognizing glucuronic acid (GlcA) or N-acetylneuraminic acid (NANA) were prepared. Simultaneous multiplexed labeling of human keratinocytes with green QDs conjugated with MIPGlcA and red QDs conjugated with MIP-NANAwas demonstrated by fluorescence imaging. The specificity of binding was verified with a non-imprinted control polymer and by enzymatic cleavage of the terminal GlcA and NANA moieties. The coating strategy is potentially a generic method for the functionalization of QDs to address a much wider range of biocompatibility and biorecognition issues. [ABSTRACT FROM AUTHOR]

A facile approach for preparation of photoluminescent (PL) carbon dots (CDs) is reported. The three resulting CDs emit bright and stable red, green and blue (RGB) colors of luminescence, under a single ultraviolet-light excitation. Alterations of PL emission of these CDs are tentatively proposed to result from the difference in their particle size and nitrogen content. Interestingly, up-conversion (UC)PL of these CDs is also observed. Moreover, flexible full-color emissive PVA films can be achieved through mixing two or three CDs in the appropriate ratios. These CDs also show low cytotoxicity and excellent cellular imaging capability. The facile preparation and unique optical features make these CDs potentially useful in numerous applications such as light-emitting diodes, full-color displays, and multiplexed (UC)PL bioimaging. [ABSTRACT FROM AUTHOR]

Aminonaphthalimide-BODIPY energy transfer cassettes were found to show very fast ( kEET≈1010-1011 s−1) and efficient BODIPY fluorescence sensitization. This was observed upon one- and two-photon excitation, which extends the application range of the investigated bichromophoric dyads in terms of accessible excitation wavelengths. In comparison with the direct excitation of the BODIPY chromophore, the two-photon absorption cross-section δ of the dyads is significantly incremented by the presence of the aminonaphthalimide donor [ δ≈10 GM for the BODIPY versus 19-26 GM in the dyad at λexc=840 nm; 1 GM (Goeppert-Mayer unit)=10−50 cm4 s molecule−1 photon−1]. The electronic decoupling of the donor and acceptor, which is a precondition for the energy transfer cassette concept, was demonstrated by time-dependent density functional theory calculations. The applicability of the new probes in the one- and two-photon excitation mode was demonstrated in a proof-of-principle approach in the fluorescence imaging of HeLa cells. To the best of our knowledge, this is the first demonstration of the merging of multiphoton excitation with the energy transfer cassette concept for a BODIPY-containing dyad. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC)‐based vaccines for immunotherapy have already achieved promising results in the last decade. To further improve current treatment protocols and enhance the therapeutic outcome, noninvasive in vivo tracking of DCs remains of crucial importance. Persistent luminescent nanoparticles (PLNPs) are inorganic materials which show an afterglow for hours after the optical excitation has ceased. If the afterglow is in the near‐infrared, the emission of injected particles can be tracked in vivo. However, stability and toxicity issues limit the use of bare PLNPs for biological applications. Therefore, appropriate surface functionalization is needed to improve their biocompatibility. In this study, it is demonstrated that near‐infrared light emitting LiGa5O8:Cr3+ nanoparticles can be functionalized with a biocompatible lipid coating which provides them with outstanding stability in biological media. In vitro experiments show efficient uptake, absence of cytotoxicity even at very high particle concentrations, and no adverse effects on the maturation potential of DCs. DCs labeled with lipid‐coated LiGa5O8:Cr3+ nanoparticles injected in mice can be imaged over days, confirming efficient in vivo migration to the popliteal lymph node. Together the results show that lipid coated LiGa5O8:Cr3+ nanoparticles possess excellent possibilities for further use in research and development of DC based vaccines. [ABSTRACT FROM AUTHOR]