Biocompatible Nanoparticles Based on Diketo‐Pyrrolo‐Pyrrole (DPP) with Aggregation‐Induced Red/NIR Emission for In Vivo Two‐Photon Fluorescence Imaging

Compared with traditional one‐photon fluorescence imaging, two‐photon fluorescence imaging techniques have shown advantages such as increased penetration depth, lower tissue autofluorescence, and reduced photo­damage, and therefore are particularly useful for imaging tissues and animals. In this work, the design and synthesis of two novel DPP ‐based compounds with large two‐photon absorption (2PA) cross‐sections (σ ≥ 8100 GM) and aggregation‐induced emission (AIE) properties are reported. The new compounds are red/NIR emissive and show large Stokes shifts (Δλ ≥ 3571 cm^?1). 1,2‐Distearoyl‐sn‐glycero‐3‐phosphoethanol amine‐N‐[maleimide(polyethylene glycol)‐2000 (DSPE‐PEG‐Mal) is used as the encapsulation matrix to encapsulate DPP‐2 , followed by surface functionalization with cell penetrating peptide (CPP) to yield DPP‐2‐CPP nanoparticles with high brightness, good water dispersibility, and excellent biocompatibility. DPP‐2 nanoparticles have been used for cell imaging and two‐photon imaging with clear visualization of blood vasculature inside mouse ear skin with a depth up to 80 μm.     

Novel Quercetin Aggregation‐Induced Emission Luminogen (AIEgen) with Excited‐State Intramolecular Proton Transfer for In Vivo Bioimaging

Aggregation‐induced emission luminogens (AIEgens) that undergo excited‐state intramolecular proton transfer (ESIPT) have many applications in bioimaging since they have high quantum efficiency in the aggregated state and a low background signal in aqueous solutions because of their large Stokes shift. One disadvantage of many of the AIEgens with ESIPT that has been described so far is that they require time‐consuming synthesis and the use of toxic reagents. Another disadvantage with most of these materials is that they are only used for bioimaging in cells and are unsuitable for in vivo bioimaging. Herein, a new AIEgen with ESIPT, quercetin (QC) is described, which is easily prepared from Sophora japonica. AIE is attributed to crystallization‐promoted keto emission. The fluorescence is temperature dependent and shows strong resistance to photobleaching. QC AIEgen with ESIPT is shown to have excellent biocompatibility and is successfully used for bioimaging both in cellular cytoplasm and in vivo.     

Bright and Photostable Organic Fluorescent Dots with Aggregation‐Induced Emission Characteristics for Noninvasive Long‐Term Cell Imaging

Efficient long‐term cell tracing in a noninvasive and real‐time manner is of great importance to understand genesis, development, invasion, and metastasis of cancerous cells. Cell penetrating organic dots with aggregation‐ induced emission (AIE) characteristics are successfully developed as long‐term cell trackers. The AIE dots enjoy the advantages of high emission efficiency, large Stokes shift, good biocompatibility, and high photostability, which ensure their good performance in long‐term non‐invasive in vitro cell tracing. Moreover, it is the first report that AIE dots exhibit certain permeability to cellular nucleus, making them attractive potential candidates for nucleus imaging. The AIE dots display superior performance compared to their counterparts of inorganic quantum dots, opening a new avenue in the development of fluorescent probes for monitoring biological processes.     

Efficient Red/Near‐Infrared Fluorophores Based on Benzo[1,2‐b:4,5‐b′]dithiophene 1,1,5,5‐Tetraoxide for Targeted Photodynamic Therapy and In Vivo Two‐Photon Fluorescence Bioimaging

Red/near‐infrared dyes are highly demanded for biological applications but most of them are far from satisfactory. In this work, a series of red/near‐infrared fluorophores based on electron‐withdrawing benzo[1,2‐b:4,5‐b′]dithiophene 1,1,5,5‐tetraoxide (BDTO) are synthesized and characterized. They possess both aggregation‐induced emission, and hybridized local and charge‐transfer characteristics. Crystallographic, spectroscopic, electrochemical and computational results reveal that the oxidation of benzo[1,2‐b:4,5‐b′]dithiophene to BDTO can endow the fluorophores with greatly red‐shifted emission, enhanced emission efficiency, reduced energy levels, enlarged two‐photon absorption cross section, and increased reactive oxygen species generation efficiency. The nanoparticles fabricated with a near‐infrared fluorophore TPA‐BDTO show high photostability and biocompatibility with good performance in targeted photodynamic ablation of cancer cells and two‐photon fluorescence imaging of intravital mouse brain vasculature.     

Robust Red Organic Nanoparticles for In Vivo Fluorescence Imaging of Cancer Cell Progression in Xenografted Zebrafish

Bright and red‐emissive organic nanoparticles (NPs) are demonstrated as promising for in vivo fluorescence imaging. However, most red organic dyes show greatly weakened or quenched emission in the aggregated state. In this work, a robust red fluorophore (t‐BPITBT‐TPE) with strong aggregate‐state photoluminescence and good biocompatibility is presented. The NPs comprised of t‐BPITBT‐TPE aggregates encapsulated within 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol) (DSPE‐mPEG) micelles exhibit a photoluminescence peak at 660 nm with a high fluorescence quantum yield of 32% in aqueous media. The NPs can be facilely charged by using the same polymeric matrix with different terminal groups, e.g., methoxy (DSPE‐mPEG), amine (DSPE‐PEG‐NH₂), or carboxymethyl (DSPE‐PEG‐COOH) groups. The biocompatibility, toxicity, circulation, and biodistribution of the NPs are assessed using the zebrafish model through whole embryo soaking and intravenous delivery. Furthermore, HeLa and MCF‐7 cells tagged with t‐BPITBT‐TPE in DSPE‐PEG‐NH₂‐TAT polymer NPs are xenografted into zebrafish larvae to successfully track the cancer cell proliferation and metastasis, demonstrating that these new NPs are efficient cancer cell trackers. In addition, the NPs also show good in vivo imaging ability toward 4T1 tumors in xenografted BALB/c mice.     

Tunable Förster Resonance Energy Transfer in Colloidal Nanoparticles Composed of Polycaprolactone‐Tethered Donors and Acceptors: Enhanced Near‐Infrared Emission and Compatibility for In Vitro and In Vivo Bioimaging

A near‐infrared (NIR) fluorescent donor/acceptor (D/A) nanoplatform based on Förster resonance energy transfer is important for applications such as deep‐tissue bioimaging and sensing. However, previously reported D/A nanoparticles (NPs) often show limitations such as aggregation‐induced fluorescence quenching and poor interfacial compatibility that reduces the efficiency of the energy transfer and also leads to leaching of the small molecular fluorophores from the NP matrix. Here highly NIR‐fluorescent D/A NPs with a fluorescence quantum yield as high as 46% in the NIR region (700–850 nm) and robust optical stability are reported. The hydrophobic core of each NP is composed of donor and acceptor moieties both of which are tethered with polycaprolactone (PCL), while the hydrophilic corona is composed of poly[oligo(ethylene glycol) methyl ether methacrylate] to offer colloidal stability and “stealthy” effect in aqueous media. The PCL matrix in each colloidal NP not only offers biocompatibility and biodegradability but also minimizes the aggregation‐caused fluorescence quenching of D/A chromophores and prevents the leakage of the NIR fluorophores from the NPs. In vivo imaging using these NIR NPs in live mice shows contrast‐enhanced imaging capability and efficient tumor‐targeting through enhanced permeability and retention effect.     

Rational Design of Perylenediimide‐Substituted Triphenylethylene to Electron Transporting Aggregation‐Induced Emission Luminogens (AIEgens) with High Mobility and Near‐Infrared Emission

Organic materials with both high electron mobility and strong solid‐state emission are rare although for their importance to advanced organic optoelectronics. In this paper, triphenylethylenes with varying number of perylenediimide (PDI) unit (TriPE‐nPDIs, n = 1?3) are synthesized and their optical and charge‐transporting properties are systematically investigated. All the molecules exhibit strong solid‐stated near infrared (NIR) emission and some of them exhibit aggregation‐enhanced emission characteristics. Organic field‐effect transistors (OFETs) using TriPE‐nPDIs are fabricated. TriPE‐3PDI shows the best performance with maximum quantum yield of ≈30% and optimized electron mobility of over 0.01 cm² V^?1 s^?1, which are the highest values among aggregation‐induced emission luminogens with NIR emissions reported so far. Photophysical property investigation and theoretical calculation indicate that the molecular conformation plays an important role on the optical properties of TriPE‐nPDI, while the result from film microstructure study reveals that the film crystallinity influences greatly their OFET device performance.     

Plasmon‐Enhanced Fluorescent Sensor based on Aggregation‐Induced Emission for the Study of Protein Conformational Transformation

The alteration in protein conformation not only affects the performance of its biological functions, but also leads to a variety of protein‐mediated diseases. Developing a sensitive strategy for protein detection and monitoring its conformation changes is of great significance for the diagnosis and treatment of protein conformation diseases. Herein, a plasmon‐enhanced fluorescence (PEF) sensor is developed, based on an aggregation‐induced emission (AIE) molecule to monitor conformational changes in protein, using prion protein as a model. Three anthracene derivatives with AIE characteristics are synthesized and a water‐miscible sulfonate salt of 9,10‐bis(2‐(6‐sulfonaphthalen‐2‐yl)vinyl)anthracene (BSNVA) is selected to construct the PEF–AIE sensor. The sensor is nearly non‐emissive when it is mixed with cellular prion protein while emits fluorescence when mixed with disease‐associated prion protein (PrP^Sc). The kinetic process of conformational conversion can be monitored through the fluorescence changes of the PEF–AIE sensor. By right of the amplified fluorescence signal, this PEF–AIE sensor can achieve a detection limit 10 pM lower than the traditional AIE probe and exhibit a good performance in human serum sample. Furthermore, molecular docking simulations suggest that BSNVA tends to dock in the β‐sheet structure of PrP by hydrophobic interaction between BSNVA and the exposed hydrophobic residues.     

Rotatable Aggregation‐Induced‐Emission/Aggregation‐Caused‐Quenching Ratio Strategy for Real‐Time Tracking Nanoparticle Dynamics

Real‐time tracking of the dynamics change of self‐assembled nanostructures in physiological environments is crucial to improving their delivery efficiency and therapeutic effects. However, such tracking is impeded by the complex biological microenvironment leading to inhomogeneous distribution. A rotatable fluorescent ratio strategy is introduced that integrates aggregation‐induced emission (AIE) and aggregation‐caused quenching (ACQ) into one nanostructured system, termed AIE and ACQ fluorescence ratio (AAR). Following this strategy, an advanced probe, PEG^5k‐TPE₄‐ICGD₄ (PTI), is developed to track the dynamics change. The extremely sharp fluorescent changes (up to 4008‐fold) in AAR allowed for the clear distinguishing and localization of the intact state and diverse dissociated states. The spatiotemporal distribution and structural dynamics of the PTI micelles can be tracked, quantitatively analyzed in living cells and animal tissue by the real‐time ratio map, and be used to monitor other responsive nanoplatforms. With this method, the dynamics of nanoparticle in different organelles are able to be investigated and validated by transmission electron microscopy. This novel strategy is generally applicable to many self‐assembled nanostructures for understanding delivery mechanism in living systems, ultimately to enhance their performance in biomedical applications.     

Red AIE‐Active Fluorescent Probes with Tunable Organelle‐Specific Targeting

Cell staining is a fascinating research area where monitoring and visualizing different cell organelles can be done using fluorescence techniques. However, the design and synthesis of organelle‐targeting fluorophores is still a challenge for several specific organelles. Herein, a platform for synthesizing efficient red‐emitting aggregation‐induced emission luminogens (AIEgens) with donor–acceptor characteristics is reported. The core molecule can be easily functionalized in order to modulate organelle targeting. The three synthesized AIEgens exhibit quantum yields of up to 39.3% and two‐photon absorption cross‐section values of up to 162 GM. The two zwitterionic AIEgens, CDPP‐3SO₃ and CDPP‐4SO_3, with the sulfonate function group, are successfully utilized for specific one‐photon and two‐photon imaging of the endoplasmic reticulum (ER) in live human cells. Substituting the zwitterionic nature with a singly positive charge group, one‐photon and two‐photon imaging of CDPP‐BzBr shows mitochondrial specificity, indicating the importance of the zwitterionic group for ER‐targeting. Owing to the good in vitro photostability, cell viability, and high efficiency, these red dyes serve as a good potential candidate for specific organelle targeting, as well as illustrate how such a platform can easily aid in the study of structure–property relationships for designing such probes.     

Off/On Fluorescent Nanoparticles for Tunable High‐Temperature Threshold Sensing

Herein, a versatile threshold temperature sensor based on the glass transition temperature‐triggered fluorescence activation of a dye/developer duo, encapsulated in polymeric nanoparticles is reported. The emission enhancement, detectable even by unaided eye is completed within a narrow temperature range and activates at adjustable threshold temperatures up to 200 °C. Fluorescence is chosen as sensing probe due to its high detection sensitivity together with an advanced spatial and temporal resolution. The strategy is based on nanoparticles prepared from standard thermoplastic polymers, a fluorescence developer, and the commercially available Rhodamine B base dye, a well‐known and widely used fluorescent molecule. By making nanoparticles of different thermoplastic polymers, fast, abrupt, and irreversible disaggregation induced fluorescence enhancement, with tunable threshold temperature depending on the nanoparticles polymer glass transition is achieved. As a proof‐of‐concept for the versatility of this novel family of NPs, their use for sensing the thermal history of environments and surfaces exposed to the threshold temperature is showed.     

Highly Efficient Circularly Polarized Electroluminescence from Aggregation‐Induced Emission Luminogens with Amplified Chirality and Delayed Fluorescence

Development of highly efficient circularly polarized organic light‐emitting diodes (CPOLEDs) has gained increasing interest as they show improved luminous efficiency and high contract 3D images in OLED displays. In this work, a series of binaphthalene‐containing luminogenic enantiomers with aggregation‐induced emission (AIE) and delayed fluorescence properties is designed and synthesized. These molecules can emit from green to red light depending on the solvent polarity due to the twisted intramolecular charge transfer effect. However, their solid powders show bright light emissions, demonstrating a phenomenon of AIE. All the molecules exhibit Cotton effects and circularly polarized luminescence in toluene solution and films. Multilayer CPOLEDs using the doped and neat films of the molecules as emitting layers are fabricated, which exhibit high external quantum efficiency of up to 9.3% and 3.5% and electroluminescence dissymmetry factor (g_EL) of up to +0.026/?0.021 and +0.06/?0.06, respectively. Compared with doped CPOLEDs, the nondoped ones show higher g_EL and much smaller current efficiency roll‐off due to the stronger AIE effect. By altering the donor unit, the electroluminescence maximum of the doped film can vary from 493 to 571 nm. As far as it is known, this is the first example of efficient CPOLEDs based on small chiral organic molecules.     

Near‐Infrared Mesoporous Silica Nanoparticles for Optical Imaging: Characterization and In Vivo Biodistribution

The characterization of near‐infrared (NIR) mesoporous silica nanoparticles (MSN) suitable for in vivo optical imaging with high efficiency is presented. Trimethylammonium groups modified MSN (MSN‐TA) with the average size of 50–100 nm was synthesized with incorporation of the TA groups into the framework of MSN. It was further adsorbed with indocyanine green (ICG) by electrostatic attraction to render MSN‐TA‐ICG as an efficient NIR contrast agent for in vivo optical imaging. The studies in stability of MSN‐TA‐ICG against pH indicated the bonding is stable over the range from acidic to physiological pH. The in vivo biodistribution of MSN‐TA‐ICG in anesthetized rat demonstrated a rather strong and stable fluorescence of MSN‐TA‐ICG that prominent in the organ of liver. Transmission electron microscopy (TEM) imaging and elemental analysis of silicon further manifested the physical and quantitative residences of MSN‐TA‐ICG in major organs. This is the first report of MSN functionalized with NIR‐ICG capable of optical imaging in vivo.     

Achieving High‐Performance Nondoped OLEDs with Extremely Small Efficiency Roll‐Off by Combining Aggregation‐Induced Emission and Thermally Activated Delayed Fluorescence

Luminescent materials with thermally activated delayed fluorescence (TADF) can harvest singlet and triplet excitons to afford high electroluminescence (EL) efficiencies for organic light‐emitting diodes (OLEDs). However, TADF emitters generally have to be dispersed into host matrices to suppress emission quenching and/or exciton annihilation, and most doped OLEDs of TADF emitters encounter a thorny problem of swift efficiency roll‐off as luminance increases. To address this issue, in this study, a new tailor‐made luminogen (dibenzothiophene‐benzoyl‐9,9‐dimethyl‐9,10‐dihydroacridine, DBT‐BZ‐DMAC) with an unsymmetrical structure is synthesized and investigated by crystallography, theoretical calculation, spectroscopies, etc. It shows aggregation‐induced emission, prominent TADF, and interesting mechanoluminescence property. Doped OLEDs of DBT‐BZ‐DMAC show high peak current and external quantum efficiencies of up to 51.7 cd A^?1 and 17.9%, respectively, but the efficiency roll‐off is large at high luminance. High‐performance nondoped OLED is also achieved with neat film of DBT‐BZ‐DMAC, providing excellent maxima EL efficiencies of 43.3 cd A^?1 and 14.2%, negligible current efficiency roll‐off of 0.46%, and external quantum efficiency roll‐off approaching null from peak values to those at 1000 cd m^?2. To the best of the authors' knowledge, this is one of the most efficient nondoped TADF OLEDs with small efficiency roll‐off reported so far.     

Water‐Soluble Biocompatible Copolymer Hypromellose Grafted Chitosan Able to Load Exogenous Agents and Copper Nanoclusters with Aggregation‐Induced Emission

A water‐soluble, positively charged polymer is obtained by copolymerizing chitosan with hypromellose, and the evaluation of its biocompatibility and the capacity for the loading of exogenous agents is performed. Films based on hypromellose grafted chitosan (HGC) are employed as a matrix to fabricate composite films by dehydration‐triggered aggregation of copper nanoclusters (NCs). The resulting HGC/Cu NC films are transparent and exhibit an aggregation‐induced emission enhancement of copper NCs, with a resulting photoluminescence quantum yield of 42%. The application of these orange emitting films as color converters for fabrication of remote light‐emitting devices is demonstrated.     

Similar or Totally Different: The Control of Conjugation Degree through Minor Structural Modifications,and Deep‐Blue Aggregation‐Induced Emission Luminogens for Non‐Doped OLEDs

Four 4,4′‐bis(1,2,2‐triphenylvinyl)biphenyl (BTPE) derivatives, 4,4′‐bis(1,2,2‐triphenylvinyl)biphenyl, 2,3′‐bis(1,2,2‐triphenylvinyl)biphenyl, 2,4′‐bis(1,2,2‐triphenylvinyl)biphenyl, 3,3′‐bis(1,2,2‐triphenylvinyl)biphenyl and 3,4′‐bis(1,2,2‐triphenylvinyl)biphenyl (oTPE‐mTPE, oTPE‐pTPE, mTPE‐mTPE, and mTPE‐pTPE, respectively), are successfully synthesized and their thermal, optical, and electronic properties fully investigated. By merging two simple tetraphenylethene (TPE) units together through different linking positions, the π‐conjugation length is effectively controlled to ensure the deep‐blue emission. Because of the minor but intelligent structural modification, all the four fluorophores exhibit deep‐blue emissions from 435 to 459 nm with Commission Internationale de l'Eclairage (CIE) chromaticity coordinates of, respectively, (0.16, 0.14), (0.15, 0.11), (0.16, 0.14), and (0.16, 0.16), when fabricated as emitters in organic light‐emitting diodes (OLEDs). This is completely different from BTPE with sky‐blue emission (0.20, 0.36). Thus, these results may provide a novel and versatile approach for the design of deep‐blue aggregation‐induced emission (AIE) luminogens.     

Precise Molecular Engineering of Photosensitizers with Aggregation‐Induced Emission over 800 nm for Photodynamic Therapy

Owing to efficient singlet oxygen (¹O₂) generation in aggregate state, photosensitizers (PSs) with aggregation‐induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high ¹O₂ generation efficiency, strong molar absorption in long‐wavelength range and near‐infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short‐wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation‐induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high ¹O₂ generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8 , which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in ¹O₂ generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application.