Stable,Wavelength‐Tunable Fluorescent Dyes in the NIR‐II Region for In Vivo High‐Contrast Bioimaging and Multiplexed Biosensing

Small‐molecule organic fluorophores, spectrally active in the 900–1700 nm region, with tunable wavelength and sensing properties are sought‐after for in vivo optical imaging and biosensing. A panel of fluorescent dyes ( CX ) has been developed to meet this challenge. CX dyes exhibit the wavelength tunability of cyanine dyes and have a rigidified polymethine chain to guarantee their stability. They are chemo‐ and photo‐stable in an aqueous environment and have tunable optical properties with maximal absorbing/emitting wavelength at 1089/1140 nm. They show great potential in high‐contrast in vivo bioimaging and multicolor detection with negligible optical cross talk. Förster resonance energy transfer (FRET) between CX dyes was demonstrated in deep tissue, providing an approach for monitoring drug‐induced hepatotoxicity by detection of OONO^?. This report presents a series of NIR‐II dyes with promising spectroscopic properties for high‐contrast bioimaging and multiplexed biosensing.     

Stable,Wavelength‐Tunable Fluorescent Dyes in the NIR‐II Region for In Vivo High‐Contrast Bioimaging and Multiplexed Biosensing

Small‐molecule organic fluorophores, spectrally active in the 900–1700 nm region, with tunable wavelength and sensing properties are sought‐after for in vivo optical imaging and biosensing. A panel of fluorescent dyes ( CX ) has been developed to meet this challenge. CX dyes exhibit the wavelength tunability of cyanine dyes and have a rigidified polymethine chain to guarantee their stability. They are chemo‐ and photo‐stable in an aqueous environment and have tunable optical properties with maximal absorbing/emitting wavelength at 1089/1140 nm. They show great potential in high‐contrast in vivo bioimaging and multicolor detection with negligible optical cross talk. Förster resonance energy transfer (FRET) between CX dyes was demonstrated in deep tissue, providing an approach for monitoring drug‐induced hepatotoxicity by detection of OONO^?. This report presents a series of NIR‐II dyes with promising spectroscopic properties for high‐contrast bioimaging and multiplexed biosensing.     

Syntheses and Fluorescent Properties of 6‐Methoxy‐2‐oxoquinoline‐3,4‐dicarbonitriles and 6,7‐Dimethoxy‐2‐oxoquinoline‐3,4‐dicarbonitriles

4‐Chlorocarbostyrils 3 , 12 , 17 , 24 , 26 with methoxy substituents in 6, 7, or 6,7‐position react with potassium cyanide in a p‐toluenesulfinate mediated reaction either to the highly fluorescent and stable 2‐oxoquinoline‐3,4‐dicarbonitriles 6 , 27 , 29 , 30 or at slightly lower temperatures to 4‐monocarbonitriles 5 , 13 , 18 . 4‐Chlorocarbostyril 3 and lithium p‐toluenesulfinate gave pure 4‐toluenesulfonylquinolone 4 , which reacted with potassium cyanide either to monocarbonitrile 5 or dicarbonitrile 6 , depending on the reaction conditions. 4‐Trifluoromethylquinolones 9 and 19 were prepared for fluorescence comparison from the appropriate methoxyaniline and 4,4,4‐trifluoroacetoacetate. The fluorescence properties such as emission wavelengths and quantum yields of 6‐methoxyderivatives 4 , 5 , 6 , 9 , 13 were studied and compared with those of 7‐methoxy derivatives 18 , 19 and 6,7‐dimethoxyderivatives 27 , 28 , 29 , 30 . 6,7‐Dimethoxy derivatives show best results, showing long‐waved fluorescence spectra up to 520 nm and acceptable quantum yields up to 0.46 for 3,4‐dicyano derivative 27 excited at 440 nm in acetonitrile.     

Multifunctional Core‐Shell‐Corona‐Type Polymeric Micelles for Anticancer Drug‐Delivery and Imaging

We have developed core‐shell‐corona‐type polymeric micelles that can integrate multiple functions in one system, including the capability of accommodating hydrophobic dyes into core and hydrophilic drug into the shell, as well as pH‐triggered drug‐release. The neutral and hydrophilic corona sterically stabilizes the multifunctional polymeric micelles in aqueous solution. The mineralization of calcium phosphate (CaP) on the PAA domain not only enhances the diagnostic efficacy of organic dyes, but also works as a diffusion barrier for the controlled release.     

Efficient NIR‐Light Emission from Solid‐State Complexes of Boron Difluoride with 2′‐Hydroxychalcone Derivatives

This article describes a series of nine complexes of boron difluoride with 2′‐hydroxychacone derivatives. These dyes were synthesized very simply and exhibited intense NIR emission in the solid state. Complexation with boron was shown to impart very strong donor–acceptor character into the excited state of these dyes, which further shifted their emission towards the NIR region (up to 855 nm for dye 5 b , which contained the strongly donating triphenylamine group). Strikingly, these optical features were obtained for crystalline solids, which are characterized by high molecular order and tight packing, two features that are conventionally believed to be detrimental to luminescence in organic crystals. Remarkably, the emission of light from the π‐stacked molecules did not occur at the expense of the emission quantum yield. Indeed, in the case of pyrene‐containing dye 4 , for example, a fluorescence quantum yield of about 15 % with a fluorescence emission maximum at 755 nm were obtained in the solid state. Moreover, dye 3 a and acetonaphthone‐based compounds 1 b , 2 b , and 3 b showed no evidence of degradation as solutions in CH₂Cl₂ that contained EtOH. In particular, solutions of brightly fluorescent compound 3 a (brightness: ε×Φ_f=45 000 M ^?1 cm^?1) could be stored for long periods without any detectable changes in its optical properties. All together, these new dyes possess a set of very interesting properties that make them promising solid‐state NIR fluorophores for applications in materials science.     

Ultrathin and Large‐area Macroporous Polymeric Membranes Formed Through Self‐assembly of Sub‐10 nm Elastic Nanoparticles

A variety of sub‐10 nm nanoparticles are successfully prepared by crosslinking of polystyrene‐b‐poly(1,3‐butadiene) (PS‐b‐PB) and polystyrene‐b‐poly(4‐vinyl pyridine) (PS‐b‐P4VP) block copolymer micelles and inverse micelles. Among them, the core‐crosslinked PS‐b‐PB micelles can self‐assemble into ultrathin (< 10 nm) macroporous (pore size <1 µm) membranes in a facile way, i.e., by simply drop‐coating the particle solution onto a mica surface. No continuous/porous membranes are produced from shell‐crosslinked PS‐b‐PB micelles and both forms of PS‐b‐P4VP micelles. This suggests that the unique structure of the block copolymer precursor, including the very flexible core‐forming block and the glassy corona‐forming block and the specific block length ratio, directly determines the formation of the macroporous membrane.

     

Polymeric nanospheres with tunable sizes,water dispersibility,and thermostability from heating‐enabled micellization of polysulfone‐block‐polyethylene glycol

Polymeric nanospheres with uniform sizes, functional surfaces, and high mechanical strength and thermostability are attracting wide interest in different applications. Here, a new kind of polysulfone micellar spheres with PEGylated surfaces is prepared via directly heating the solution of an amphiphilic block copolymer, polysulfone‐b‐polyethylene glycol (PSF‐b‐PEG). The sizes of the micelles are uniform and tunable between ∼42 and ∼443 nm. TEM characterizations show that the micelles are core‐shell structures with PEG as the corona and PSF as the core. PEG endows the micelles with dispersibility in water and good biocompatibility, while PSF provides the mechanical strength and thermostability. The effects of PEG contents, polymer solution concentrations, solvent types, and heating temperatures are systematically investigated. Furthermore, heat resistance tests show that the micelles are stable at 150–180 °C. These PSF‐b‐PEG micellar spheres are expected to be applied in demanding environmental conditions such as heating involved surface modification process. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 769–777     

Amine‐Reactive PEGylated Nanoparticles for Potential Bioconjugation

Water‐dispersible PEGylated nanoparticles (NPs) presenting amine‐reactive conjugation sites at their surfaces were synthesized and their ability to react with amines was demonstrated. An amphiphilic block copolymer bearing an N‐succinimidyl ester at its water‐soluble end was synthesized by the consecutive controlled radical polymerization of poly(ethylene glycol) methacrylate and styrene from a functional halide initiator. After purification of the copolymer, NPs of approximately 40 nm were obtained by a self‐assembly process in water. The reactivity of the NPs was evidenced by reacting them with primary amines, including a fluorescent dye. The activated ester remained stable throughout all synthetic steps and a nearly quantitative coupling efficiency was obtained.

     

Efficient blue‐green‐emitting poly[(5‐diphenylamino‐1,3‐phenylenevinylene)‐alt‐(2,5‐dihexyloxy‐1,4‐phenylenevinylene)] derivatives: Synthesis and optical properties

New poly(phenylene vinylene) derivatives with a 5‐diphenylamino‐1,3‐phenylene linkage (including polymers 2 , 3 , and 5 ) have been synthesized to improve the charge‐injection properties. These polymers are highly photoluminescent with fluorescent quantum yields as high as 76% in tetrahydrofuran solutions. With effective π‐conjugation interruption at adjacent m‐phenylene units, chromophores of different conjugation lengths can be incorporated into the polymer chain in a controllable manner. In polymer 2 , the structural regularity leads to an isolated, well‐defined emitting chromophore. Isomeric polymer 3 of a random chain sequence, however, allows the effective emitting chromophores to be joined in sequence by sharing a common m‐phenylene linkage (as shown in a molecular fragment). Double‐layer light‐emitting‐diode devices using 2 , 3 , and 5 as emitting layers have turn‐on voltages of about 3.5 V and produce blue‐green emissions with peaks at 493, 492, and 482 nm and external quantum efficiencies up to 1.42, 0.98, and 1.53%, respectively. In comparison with a light‐emitting diode using 2 , a device using 3 shows improved charge injection and displays increased brightness by a factor of ～3 to 1400 cd/m² at an 8‐V bias. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2307–2315, 2006     

Local viscosity analysis of triblock copolymer micelle with cyanine dyes as a fluorescent probe

The local viscosity of Pluronic F127 triblock copolymer micelles in water was determined with cyanine dyes as fluorescent probes. These dyes show very weak fluorescence at a low temperature, but show enhanced fluorescence at a temperature higher than the critical micellization temperature (T(cm)). This is because a viscous environment within the micelle suppresses the formation of a nonradiative twisted intramolecular charge transfer (TICT) excited state of the dyes. The good correlation between the fluorescence quantum yields of the dyes and the viscosity and the temperature of the media allows a determination of local viscosity of micelle based on the fluorescence quantum yields. The local viscosity of both core and corona regions of micelles increases at >T(cm) and shows a maximum at a temperature 7-9 °C higher than T(cm), and decreases at higher temperature due to the increased fluidity. The core viscosity is larger than that of the corona, and the corona viscosity increases toward the micelle center. The polymer concentration has different effects on the core and corona viscosity: the corona viscosity increases with a polymer concentration increase at the entire temperature range, whereas the core viscosity increases only at a low temperature. The corona viscosity increase is due to the condensation of a large number of polyethylene oxide (PEO) blocks. In contrast, the dehydration degree of polypropylene oxide (PPO) blocks in the core scarcely changes, and the core has a similar composition regardless of polymer concentration. The larger polymer concentration promotes a micelle formation at lower temperature where the fluidity increase is very weak, resulting in larger core viscosity.     

Core Cross‐Linked Micelle‐Based Nanoreactors for Efficient Photocatalysis

Stable nanoscale cross‐linked polymer micelles containing Ru complexes (Ru‐CMs) were prepared from monomethoxy[poly(ethylene glycol)]‐block‐poly(L ‐lysine) (MPEG‐PLys) and [(bpy)₂Ru(fmbpy)](PF₆)₂ (bpy=bipyridine, fmbpy=5‐formy‐5′‐methyl‐2,2′‐bipyridine). To stabilize the micelles, bifunctional glutaraldehyde was used as a cross‐linker to react with the free amino groups of the PLys block. After that, the Ru‐CMs showed very good stability in common solvents. The Ru‐CMs showed photocatalytic activity and selectivity in the oxidation of sulfides that were as high as those of the well‐known [Ru(bpy)₃(PF₆)₂] complex, because the micelles were swollen in the methanol–sulfide mixture. Moreover, because of the nanoscale size of the particles and their high stability, the Ru‐CM photocatalysts can be readily recovered by ultrafiltration and reused without loss of photocatalytic activity. This work highlights the potential of using cross‐linked micelles as a platform for developing highly efficient heterogeneous photocatalysts for a number of important organic transformations.     

The self‐assembly over nano‐ to submicro‐length scales in water of a fluorescent julolidine‐labeled amphiphilic random terpolymer

A novel fluorescent‐labeled amphiphilic random terpolymer is synthesized by controlled radical polymerization of a fluorescent molecular rotor monomer, 2‐cyano‐2‐[4‐vinyl(1,1′‐biphenyl)‐4′‐yl]vinyljulolidine, a hydrophilic monomer, poly (ethylene glycol) methyl ether methacrylate, and a hydrophobic monomer, perfluorohexylethyl acrylate. Combined dynamic light scattering and fluorescence emission spectroscopy measurements are used to investigate its self‐assembly in water solution. Self‐assembled nanostructures with a hydrodynamic diameter size D_h of 4 ± 1 nm are detected due to the single‐chain folding of the terpolymer in unimer micelles. The fluorescence emission intensity of the terpolymer in water solution is found to be one order of magnitude higher than that in organic solvents, as a result of the preferential encapsulation of the julolidine co‐units in hydrophobic compartments of the unimer micelles. The temperature dependence of the self‐associative behavior of the amphiphilic terpolymer is also investigated and a critical temperature is identified at which a transition between single‐chain unimer micelles and multi‐chain aggregates (D_h = 400 ± 40 nm) reversibly takes place on heating–cooling cycles. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 797–804     

A Red to Near‐IR Fluorogen: Aggregation‐Induced Emission,Large Stokes Shift,High Solid Efficiency and Application in Cell‐Imaging

A tetraphenylethene (TPE) derivative modified with the strong electron acceptor 2‐dicyano‐methylene‐3‐cyano‐4,5,5‐trimethyl‐2,5‐dihydrofuran (TCF) was obtained in high yield by a simple two‐step reaction. The resultant TPE‐TCF showed evident aggregation‐induced emission (AIE) features and pronounced solvatochromic behavior. Changing the solvent from apolar cyclohexane to highly polar acetonitrile, the emission peak shifted from 560 to 680 nm (120 nm redshift). In an acetonitrile solution and in the solid powder, the Stokes shifts are as large as 230 and 190 nm, respectively. The solid film emits red to near‐IR (red‐NIR) fluorescence with an emission peak at 670 nm and a quantum efficiency of 24.8 %. Taking the advantages of red‐NIR emission and high efficiency, nanoparticles (NPs) of TPE‐TCF were fabricated by using tat‐modified 1,2‐distearoylsn‐glycero‐3‐phosphor‐ethanol‐amine‐N‐[methoxy‐(polyethyl‐eneglycol)‐2000] as the encapsulation matrix. The obtained NPs showed perfect membrane penetrability and high fluorescent imaging quality of cell cytoplasm. Upon co‐incubation with 4,6‐diamidino‐2‐phenylindole (DAPI) in the presence of tritons, the capsulated TPE‐TCF nanoparticles could enter into the nucleus and displayed similar staining properties to those of DAPI.     

Continuous and Segmented Semiconducting Fiber‐like Nanostructures with Spatially Selective Functionalization by Living Crystallization‐Driven Self‐Assembly

Fiber‐like π‐conjugated nanostructures are important components of flexible organic electronic and optoelectronic devices. To broaden the range of potential applications, one needs to control not only the length of these nanostructures, but the introduction of diverse functionality with spatially selective control. Here we report the synthesis of a crystalline‐coil block copolymer of oligo(p‐phenylenevinylene)‐b‐poly(2‐vinylpyridine) (OPV₅‐b‐P2VP₄₄), in which the basicity and coordinating/chelating ability of the P2VP segment provide a landscape for the incorporation of a variety of functional inorganic NPs. Through a self‐seeding strategy, we were able to prepare monodisperse fiber‐like micelles of OPV₅‐b‐P2VP₄₄ with lengths ranging from 50 to 800 nm. Significantly, the exposed two ends of OPV core of these fiber‐like micelles remained active toward further epitaxial deposition of OPV₅‐b‐PNIPAM₄₉ and OPV₅‐b‐P2VP₄₄ to generate uniform A‐B‐A and B‐A‐B‐A‐B segmented block comicelles with tunable lengths for each block. The P2VP domains in these (co‐)micelles can be selectively decorated with inorganic and polymeric nanoparticles as well as metal oxide coatings, to afford hybrid fiber‐like nanostructures. This work provides a versatile strategy toward the fabrication of narrow length dispersity continuous and segmented π‐conjugated OPV‐containing fiber‐like micelles with the capacity to be decorated in a spatially selective way with varying functionalities.     

Supra-Cyanines: Ultrabright Cyanine-Based Fluorescent Supramolecular Materials in Solution and in the Solid State

Fluorescent materials with high brightness play a crucial role in the advancement of various technologies such as bioimaging, photonics, and OLEDs. While significant efforts are dedicated to designing new organic dyes with improved performance, enhancing the brightness of existing dyes holds equal importance. In this study, we present a simple supramolecular strategy to develop ultrabright cyanine-based fluorescent materials by addressing long-standing challenges associated with cyanine dyes, including undesired cis-trans photoisomerization and aggregation-caused quenching. Supra-cyanines are obtained by incorporating cyanine moieties in a cyclic peptide-based supramolecular scaffold, and exhibit high fluorescence quantum yields (up to 50 %) in both solution and in the solid state. These findings offer a versatile approach for constructing highly emissive cyanine-based supramolecular materials.     

Micelles‐Encapsulated Microcapsules for Sequential Loading of Hydrophobic and Water‐Soluble Drugs

Layer‐by‐layer (LbL) assembly was conducted on CaCO₃ microparticles pre‐doped with polystyrene‐block‐poly(acrylic acid) (PS‐b‐PAA) micelles, and resulted in micelles encapsulation in the microcapsules after core removal. Distribution of the micelles in the templates and capsules was characterized by transmission electron microscopy and confocal laser scanning microscopy. The micelles inside the capsules connected with each other to form a chain and network‐like structure with a higher density near the capsule walls. The hydrophobic PS cores were then able to load small uncharged hydrophobic drugs while the negatively charged PAA corona could induce spontaneous deposition of water‐soluble positively charged drugs such as doxorubicin.

     

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol copolymer based shell cross‐linked micelles for controlled release of drug

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol (PPC‐b‐APEG) copolymer was synthesized by the click chemistry, and its structure were characterized. PPC‐b‐APEG can self‐assemble into micelles without emulsifier in water. Shell cross‐linked micelles were obtained by the reaction of the allyloxy groups, which were exposed on the outer of the PPC‐b‐APEG micelles, and N‐vinylpyrrolidone (NVP). The morphology and size of the micelles before and after cross‐link reactions were characterized. The research result shows that the shell cross‐linking could improve the stability of micelles. The particle size of uncross‐linked micelle was about 800 nm. The size of cross‐linked micelles increased with increasing amount of cross‐linking degree. To better evaluate the release behavior of PPC‐b‐PEG copolymer, doxorubicin (DOX)‐loaded micelles were synthesized using DOX as the model drug. Results showed that the DOX releasing rate decreased with increasing of NVP. The shell cross‐linking do decrease the burst release behaviours of DOX and reduce the DOX release rate.     

A New Class of Blue‐LED‐Excitable NIR‐II Luminescent Nanoprobes Based on Lanthanide‐Doped CaS Nanoparticles

Lanthanide (Ln³⁺)‐doped luminescent nanoparticles (NPs) with emission in the second near‐infrared (NIR‐II) biological window have shown great promise but their applications are currently limited by the low absorption efficiency of Ln³⁺ owing to the parity‐forbidden 4f→4f electronic transition. Herein, we developed a strategy for the controlled synthesis of a new class of NIR‐II luminescent nanoprobes based on Ce³⁺/Er³⁺ and Ce³⁺/Nd³⁺ co‐doped CaS NPs, which can be effectively excited by using a low‐cost blue light‐emitting diode chip. Through sensitization by the allowed 4f→5d transition of Ce³⁺, intense NIR‐II luminescence from Er³⁺ and Nd³⁺ with quantum yields of 9.3 % and 7.7 % was achieved, respectively. By coating them with a layer of amphiphilic phospholipids, these NPs exhibit excellent stability in water and can be exploited as sensitive NIR‐II luminescent nanoprobes for the accurate detection of an important disease biomarker, xanthine, with a detection limit of 32.0 nm .     

Synthesis,self‐assembly,and formation of photo‐crosslinking‐stabilized fluorescent micelles covalently containing zinc(II)‐bis(8‐hydroxyquinoline) for ABC triblock copolymer bearing cinnamoyl and 8‐hydroxyquinoline side groups

Triblock copolymers (MPEG‐b‐PCEMA‐b‐PHQHEMA) bearing cinnamoyl and 8‐hydroxyquinoline side groups with different block length are synthesized by a two‐step reversible addition fragmentation chain transfer polymerization of cinnamoyl ethyl methacrylate (CEMA) and 2‐((8‐hydroxyquinolin‐5‐yl)methoxy)ethyl methacrylate (HQHEMA), respectively. The self‐assembly of MPEG‐b‐PCEMA‐b‐PHQHEMA in mixture of THF and ethanol is investigated by varying the ratio of THF and ethanol. Spheric micelles with diameter of 63.7 nm and polydispersity of 0.128 are obtained for MPEG₁₁₃‐b‐PCEMA₁₅‐b‐PHQHEMA₁₇ in THF/ethanol with a volume ratio (v/v) of 5/5. The PCEMA inner shell of the resulted micelles is photo‐crosslinked under UV radiation to give stabilized micelles. The complex reaction of the stabilized micelles with Zn(II) is investigated under different conditions to give zinc(II)‐bis(8‐hydroxyquinoline)(Znq₂)‐containing micelles. When the complex reaction is carried out in THF/ethanol (v/v = 5/5) or THF/toluene (v/v = 6/4) with zinc acetate, fluorescent Znq₂‐containing micelles are obtained without obvious change in diameters and morphologies. The fluorescent micelles exhibit green emission with λ_max at 520 nm. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1056–1064     

Decomposition‐Assembly of Tetraphenylethylene Nanoparticles With Uniform Size and Aggregation‐Induced Emission property

Tetraphenylethylene (TPE)‐substituted poly(allylamine hydrochloride) (PAH‐g‐TPE) is synthesized by a Schiff base reaction between PAH and TPE‐CHO. The PAH‐g‐TPE forms micelles in water at pH 6, which are further transformed into pure TPE‐CHO nanoparticles (NPs) with a diameter of ≈300 nm after incubation in a solution of low pH value. In contrast, only amorphous precipitates are obtained when TPE‐CHO methanol solution is incubated in water. The aggregation‐induced emission feature of the TPE molecule is completely retained in the TPE NPs, which can be internalized into cells and show blue fluorescence. Formation mechanism of the TPE NPs is proposed by taking into account the guidance effect of linear and charged PAH molecules, and the propeller‐stacking manner between the TPE‐CHO molecules.