Photoprogrammable circularly polarized phosphorescence switching of chiral helical polyacetylene thin films.

The developments of pure organic room-temperature phosphorescence (RTP) materials with circularly polarized luminescence (CPL) have significantly facilitated the future integration and systemization of luminescent material in fundamental science and technological applications. Here, a type of photoinduced circularly polarized RTP materials are constructed by homogeneously dispersing phosphorescent chiral helical substituted polyacetylenes into a processable poly(methyl methacrylate) (PMMA) matrix. These substituted polyacetylenes play vital roles in the propagation of CPL and present prominently optical characteristics with high absorption and luminescent dissymmetric factors up to 0.029 (gabs) and 0.019 (glum). The oxygen consumption properties of the films under UV light irradiation endow materials with dynamic chiro-optical functionality, which can leverage of light to precisely control and manipulate the circularly polarized RTP properties with the remarkable advantages of being contactless, wireless and fatigue-resistant. Significantly, the distinct materials with dynamic properties can be used as anti-counterfeiting materials involving photoprogrammability.

Highly efficient organic long persistent luminescence based on host-guest doping systems.

Recently, organic long persistent luminescence (OLPL) has attracted widespread attention as a new luminescence pathway initiated by the exciplex. However, the low quantum yield, few alternative molecules and high fabrication cost seriously slow down the development of OLPL materials. Herein, a series of simple multi-guest/host OLPL materials with a high quantum yield are reported by doping four phenothiazine derivative guest molecules into 9H-xanthen-9-one host matrices. The F-substituted phenothiazine derivative doping system displays highly efficient emission with 46.3% quantum yield in air. Meanwhile, these OLPL materials provide broad opportunities for further application in the field of heat resistance due to their highly efficient luminescence at high temperatures.

A Universal Strategy for Tunable Persistent Luminescent Materials via Radiative Energy Transfer.

In this work, a universal strategy for solid, solution, or gel state organic persistent luminescent materials via radiative energy transfer is proposed. The persistent luminescence (τ>0.7 s) could be remotely regulated between different colors by controlling the isomerization of the energy acceptor. The function relies on the simple radiative energy transfer (reabsorption) mechanism, rather than the complicated communication between the excited state of the molecules such as Förster resonance energy transfer or Dexter energy transfer. And the "apparent lifetime" for the energy acceptor is the same as the lifetime of the energy donor, which was different with a traditional radiative energy transfer process. The simple working principle endows this strategy with huge universality, flexibility, and operability. This work offers a simple, feasible, and universal way to construct various persistent luminescent materials in solid, solution, and gel states.

A Simple, Easy Preparation and Tunable Strategy for Preparing Organic Room-Temperature Phosphorescence.

Eye-catching organic room-temperature phosphorescence (RTP) is becoming more and more universal through various strategies, such as crystal engineering, macrocyclic inclusion, host-guest doping, and copolymerization. It is always the pursuit of researchers to prepare high-efficiency RTP materials by the simplest strategy. The doping strategy is one of the most simple and effective strategies and involves mixing phosphor with rigid host material. The principle of the doping RTP system has developed from a conventional rigidity effect of the host through the host-guest interaction. This perspective aims at multifunctional host materials and summarizes the recent development of doping organic RTP systems. Doping systems play more and more important roles in the development of long-afterglow and high-yield RTP materials. The application scenarios of RTP are becoming wider and wider.

Synergistic strategy of rare-earth doped nanoparticles for NIR-II biomedical imaging.

Featuring simultaneous multicolor imaging for multiple targets, a synergistic strategy has become promising for fluorescence imaging applications. Visible and first near infrared (NIR-I, 700-900 nm) fluorophores have been explored for multicolor imaging to achieve good multi-target capacity, but they are largely hampered by the narrow imaging bands available (400-900 nm, bandwidth 500 nm), the broad emission spectra of many fluorophores, shallow tissue penetration and scattering loss. With attractive characteristic emission peaks in the second NIR window (NIR-II, 1000-1700 nm), a narrow emission spectrum, and deeper tissue penetration capability, rare-earth doped nanoparticles (RENPs) have been considered by us to be outstanding candidates for multicolor bioimaging. Herein, two RENPs, NaYF4:Yb20Er2@NaYF4 and NaYF4:Nd5@NaYF4, were prepared and modified with polyethylene glycol (PEG) to explore simultaneous imaging in the NIR-IIb (1530 nm, under 980 nm laser excitation) and the NIR-II (1060 nm, under 808 nm laser excitation) windows. The PEGylated-RENPs (RENPs@PEG) were able to simultaneously visualize the circulatory system, trace the lymphatic system, and evaluate the skeletal system. Our study demonstrates that RENPs have high synergistic imaging capability in multifunctional biomedical applications using their NIR-II fluorescence. Importantly, the two RENPs@PEG are complementary to each other for higher temporal resolution in NaYF4:Nd5@NaYF4@PEG and higher spatial resolution in NaYF4:Yb20Er2@NaYF4@PEG, which may provide more comprehensive and accurate imaging diagnosis. In conclusion, RENPs are highly promising nanomaterials for multicolor imaging in the NIR-II window.

Engendering persistent organic room temperature phosphorescence by trace ingredient incorporation.

Pure organic persistent room temperature phosphorescence (RTP) has shown great potential in information encryption, optoelectronic devices, and bio-applications. However, trace impurities are generated in synthesis, causing unpredictable effects on the luminescence properties. Here, an impurity is isolated from a pure organic RTP system and structurally characterized that caused an unusual ultralong RTP in matrix even at 0.01 mole percent content. Inspired by this effect, a series of compounds are screened out to form the bicomponent RTP system by the trace ingredient incorporation method. The RTP quantum yields reach as high as 74.2%, and the lifetimes reach up to 430 ms. Flexible application of trace ingredients to construct RTP materials has become an eye-catching strategy with high efficiency, economy, and potential for applications as well as easy preparation.

Smart Self-Assembly Amphiphilic Cyclopeptide-Dye for Near-Infrared Window-II Imaging.

Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near-infrared window (NIR-II, 1000-1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH-sensitive self-assembling cyclopeptide-dye, SIMM1000, as a smart nanoprobe for NIR-II imaging of diseases in living animals, is reported. This small molecule assembled nanoprobe exhibits smart properties by responding to a sharp decrease of pH in the tumor microenvironment (pH 7.0 to 6.8), aggregating from small nanoprobe (80 nm at pH 7.0) into large nanoparticles (>500 nm at pH 6.8) with ≈20-30 times enhanced fluorescence compared with the non-self-assembled CH-4T. It yields micrometer-scale resolution in blood vessel imaging and high contrast and resolution in bone and tumor imaging in mice. Because of its self-aggregation in acidic tumor microenvironments in situ, SIMM1000 exhibits high tumor accumulation and extremely long tumor retention (>19 days), while being excretable from normal tissues and safe. This smart self-assembling small molecule strategy can shift the paradigm of designing new nanomaterials for molecular imaging and drug development.

ApoE4 (Δ272-299) induces mitochondrial-associated membrane formation and mitochondrial impairment by enhancing GRP75-modulated mitochondrial calcium overload in neuron.

BACKGROUND: Apolipoprotein E4 (apoE4) is a major genetic risk factor of Alzheimer's disease. Its C-terminal-truncated apoE4 (Δ272-299) has neurotoxicity by affecting mitochondrial respiratory function. However, the molecular mechanism(s) underlying the action of apoE4 (Δ272-299) in mitochondrial function remain poorly understood. METHODS: The impact of neuronal apoE4 (Δ272-299) expression on ER stress, mitochondrial-associated membrane (MAM) formation, GRP75, calcium transport and mitochondrial impairment was determined in vivo and in vitro. Furthermore, the importance of ER stress or GRP75 activity in the apoE4 (Δ272-299)-promoted mitochondrial dysfunction in neuron was investigated. RESULTS: Neuronal apoE4 (Δ272-299) expression induced mitochondrial impairment by inducing ER stress and mitochondrial-associated membrane (MAM) formation in vivo and in vitro. Furthermore, apoE4 (Δ272-299) expression promoted GRP75 expression, mitochondrial dysfunction and calcium transport into the mitochondria in neuron, which were significantly mitigated by treatment with PBA (an inhibitor of ER stress), MKT077 (a specific GRP75 inhibitor) or GRP75 silencing. CONCLUSIONS: ApoE4 (Δ272-299) significantly impaired neuron mitochondrial function by triggering ER stress, up-regulating GRP75 expression to increase MAM formation, and mitochondrial calcium overload. Our findings may provide new insights into the neurotoxicity of apoE4 (Δ272-299) against mitochondrial function and uncover new therapeutic targets for the intervention of Alzheimer's disease.

Reversible room-temperature phosphorescence in response to light stimulation based on a photochromic copolymer.

In the field of intelligent luminescence materials, it is a great challenge to regulate organic room-temperature phosphorescence by light irradiation. Herein, benzothiadiazole was modified with viologen derivatives and copolymerized to achieve amorphous RTP emission. The photo-stimulated color change in both emission and absorption has a good reversibility after cycles of light irradiation.

Tunable-Emission Amorphous Room-Temperature Phosphorescent Polymers Based on Thermoreversible Dynamic Covalent Bonds.

Pure organic room-temperature phosphorescence (RTP) materials are useful for photoelectric, biochemical devices, and bioimaging sensors. In the last few years, dynamic covalent chemistry has aroused substantial attention as it offers a way to create intelligent materials with feedback and response functions. Through a Diels-Alder reaction, a [4+2] cycloaddition reaction between dienes and dienophiles, three polymers were synthesized that can be reversibly transformed by thermally reversible dynamic covalent bonds. All polymers show decent RTP emission with different colors. For the poly-Br-An solid, the absolute phosphorescence quantum yield reaches up to 12 %. This study provides a new method for the rational design and synthesis of tunable-emission organic RTP materials via dynamic covalent bonds.

Reactive oxygen species and enzyme dual-responsive biocompatible drug delivery system for targeted tumor therapy.

Spurred by newly developed drug delivery systems (DDSs), side effects of cancer chemotherapy could be reduced by using multifunctional nanoplatforms. However, the facile synthesis of effective DDSs remains a challenge. Here, a six-arginine-tailed anti-epidermal growth factor receptor (EGFR) affibody was employed to easily synthesize the highly reactive oxygen species (hROS)- and trypsin-responsive 11-mercaptoundecanoic acid-modified gold nanoclusters (MUA-Au NCs) for tumor-targeted drug delivery. The polyarginine moiety of affibody sealed methotrexate (MTX)-loaded MUA-Au NCs through charge effect, as well as leaving the rest targeting fragment of the affibody to specifically bind tumor overexpressed EGFR. As the shell of MUA-Au NCs-MTX-Affibody (MAMA), polyarginine chains of affibody could be digested by trypsin, helping to release MTX from MAMA. The released MTX accelerated destroying MUA-Au NCs through inducing the generation of hROS. Specifically targeting EGFR-overexpressed tumors, quickly delivering a sufficient amount of drug to the tumor, subsequently increasing the local MTX and hROS levels, and safely eliminating the biocompatible structure from kidney, endowed MAMA greater treatment effectiveness and lower side effect than chemotherapy, especially in pancreatic cancer due to its high trypsin level. This simply fabricated DDS may find applications in high effective cancer therapy, especially for tumors with high trypsin activity.

A thiopyrylium salt for PET/NIR-II tumor imaging and image-guided surgery.

All tumor imaging modalities have resolution limits below which deeply situated small metastatic foci may not be identified. Moreover, incomplete lesion excision will affect the outcomes of the patients. Scintigraphy is adept in locating lesions, and second near-infrared window (NIR-II) imaging may allow precise real-time tumor delineation. To achieve complete excision of all lesions, multimodality imaging is a promising method for tumor identification and management. Here, a NIR-II thiopyrylium salt, XB1034, was first synthesized and bound to cetuximab and trans-cyclooctene (TCO) to produce XB1034-cetuximab-TCO. This probe provides excellent sensitivity and high temporal resolution NIR-II imaging in mice bearing tumors developed from human breast cancer cells MDA-MB-231. To enable PET imaging, 68 Ga-NETA-tetrazine is subsequently injected into the mice to undergo a bio-orthogonal reaction with the preinjected XB1034-cetuximab-TCO. PET images achieved in the tumor models using the pretargeting strategy are of much higher quality than those obtained using the direct radiolabeling method. Moreover, real-time NIR-II imaging allows accurate tumor excision and sentinel lymph node mapping. In conclusion, XB1034 is a promising molecular imaging probe for tumor diagnosis and treatment.

Facile Synthesis of Nitrogen-Containing Six-Membered Benzofuzed Phenophosphazinine Oxides and Studies of the Photophysical Properties.

A facile synthesis of nitrogen-containing six-membered benzofuzed phosphacycles has been described. This cyclization reaction triggered by Tf2O provides an expedient protocol of phosphacycles with a simple operation at mild conditions. The preliminary photophysical studies of these novel materials reveal that the fluorescence intensity enhances with the molecular aggregation in the solid state and that the introduction of the sterically bulky phenanthrene group into the phosphacycles allows a significant increase in the fluorescence quantum yield.

[Effects of soil water stress and atmospheric CO2 concentration on photosynthetic and post-photosynthetic fractionation].

Analysis of plant photosynthesis and post-photosynthetic fractionation can improve our understanding of plant physiology and water management. By measuring δ13C in the atmosphere, and δ13C of soluble compounds in leaves and branch phloem of Platycladus orientalis, we examined discrimination pattern, including atmosphere-leaf discrimination during photosynthesis (ΔCa-leaf) and leaf-twig discrimination during post-photosynthesis (ΔCleaf-phlo), in response to changes of soil water content (SWC) and atmospheric CO2 concentration (Ca). The results showed that ΔCa-leaf reached a maximum of 13.06‰ at 95%-100% field water-holding capacity (FC) and Ca 400 µmol·mol-1, and a minimum of 8.63‰ at 35%-45% FC and Ca 800 µmol·mol-1. Both stomatal conductance and mesophyll cell conductance showed a significant linear positive correlation with ΔCa-leaf, with a correlation coefficient of 0.43 and 0.44, respectively. ΔCleaf-phlo was not affected by SWC and Ca. Our results provide mechanism of carbon isotopes fractionation and a theoretical basis for plant survival strategies in response to future climate change.

Novel near-infrared II aggregation-induced emission dots for in vivo bioimaging.

Near-infrared II fluorescence imaging holds great promise for in vivo imaging and imaging-guided surgery with deep penetration and high spatiotemporal resolution. However, most NIR-II aromatic luminophores suffer from the notorious aggregation-caused quenching (ACQ) effect in the aqueous solution, which largely hinders their biomedical application in vivo. In this study, the first NIR-II organic aggregation-induced emission (AIE) fluorophore (HLZ-BTED), encapsulated as nanoparticles (HLZ-BTED dots) for in vivo biomedical imaging, was designed and synthesized. The NIR-II AIE HLZ-BTED dots showed high temporal resolution, high photostability, outstanding water-solubility and biocompatibility in vitro and in vivo. The HLZ-BTED dots were further used for long-term breast tumor imaging and visualizing tumor-feeding blood vessels, long-term hind limb vasculature and incomplete hind limb ischemia. More importantly, as a proof-of-concept, this is the first time that non-invasive and real-time NIR-II imaging of the gastrointestinal tract in health and disease has been performed, making the AIE dots a promising tool for gastrointestinal (GI) tract research, such as understanding the healthy status of GI peristalsis, diagnosing and evaluating intestinal motility dysfunction, and assessing drug effects on intestinal obstruction.

Quaternary Ammonium Salt Based NIR-II Probes for in vivo Imaging.

Traditional luminescent materials including fluorescent probes suffer from notorious aggregation-caused quenching (ACQ) in aqueous solutions. Although several approaches such as the aggregation-induced emission (AIE) effect have been developed, it remains a significant challenge to identify an effective and efficient strategy to resolve this issue. Herein, quaternary ammonium salts Q8PBn and Q8PNap as a novel class of bright near infrared window II (NIR-II, 1,000 - 1,700 nm) probes were designed and synthesized, and the twisted intramolecular charge transfer (TICT) formation at the excited state can be effectively suppressed for the newly designed probes. Furthermore, Q8PNap complexation with fetal bovine serum (Q8PNap/FBS) significantly increased the quantum yield by ~ 32-fold compared with PEGylated tertiary amine Q8P, and Q8PNap/FBS was successfully used to achieve high spatial and temporal resolution imaging of hind limb vasculature, lymphatic system, and small tumor metastasis, as well as precise NIR-II imaging-guided tumor and lymph node surgery in small animal models for the first time.

Polymethine Thiopyrylium Fluorophores with Absorption beyond 1000 nm for Biological Imaging in the Second Near-Infrared Subwindow.

Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by the indocyanine green structure, a series of polymethine dyes with both absorption and emission in the NIR-II window have been developed for NIR-II imaging, providing the feasibility to directly compare optical imaging in the NIR-IIa (1300-1400 nm) subwindow under 1064 nm excitation with that in the NIR-II window under 808 nm excitation. The signal-background ratio and the tumor-normal tissue ratio achieved great improvement under 1064 nm excitation in the imaging of mouse blood pool and U87 glioma tumors. Our study not only introduces a broadband emission fluorophore for both NIR-II and NIR-IIa imaging, but also reveals the advantages of NIR-II excitation over NIR-I in in vivo imaging.

Molecular Targeted NIR-II Probe for Image-Guided Brain Tumor Surgery.

Optical imaging strategies for improving delineation of glioblastoma (GBM) is highly desired for guiding surgeons to distinguish cancerous tissue from healthy and precious brain tissue. Fluorescence imaging (FLI) in the second near-infrared window (NIR-II) outperforms traditional NIR-I imaging with better tissue penetration, higher spatial and temporal resolution, and less auto fluorescence and scattering. Because of high expression in GBM and many other tumors, urokinase Plasminogen Activator Receptor (uPAR) is an attractive and well proven target for FLI. Herein we aim to combine the benefit of a NIR-II fluorophore with a high affinity uPAR targeting small peptide. A targeted NIR-II fluorescent probe was developed by conjugating an in-house synthesized NIR-II fluorophore, CH1055, and a uPAR targeting peptide, AE105. To characterize the in vivo distribution and targeting properties, a dynamic imaging was performed in orthotopic GBM bearing nude mice ( n = 8). Additionally, fluorescence guided surgery of orthotopic GBM was performed in living animals. CH1055-4Glu-AE105 was easily synthesized with >75% yield and >98% HPLC evaluated purity. The retention time of the probe on analytical HPLC was 15.9 min and the product was verified by mass spectrometry. Dynamic imaging demonstrated that the uPAR targeting probe visualized orthotopic GBM through the intact skull with a tumor-to-background ratio (TBR) of 2.7 peaking at 96 h. Further, the orthotopic GBM was successfully resected in small animals guided by the NIR-II FLI. By using a small uPAR targeting NIR-II probe, FLI allows us to specifically image and detect GBM. A real-time imaging setup further renders FLI guided tumor resection, and the probe developed in this work is a promising candidate for clinical translation.

Novel bright-emission small-molecule NIR-II fluorophores for in vivo tumor imaging and image-guided surgery.

Though high brightness and biocompatible small NIR-II dyes are highly desirable in clinical or translational cancer research, their fluorescent cores are relatively limited and their synthetic processes are somewhat complicated. Herein, we have explored the design and synthesis of novel NIR-II fluorescent materials (H1) without tedious chromatographic isolation with improved fluorescence performance (QY ≈ 2%) by introducing 2-amino 9,9-dialkyl-substituted fluorene as a donor into the backbone. Several types of water-soluble and biocompatible NIR-II probes: SXH, SDH, and H1 NPs were constructed via different chemical strategies based on H1, and then their potential to be used in in vivo tumor imaging and image-guided surgery in the NIR-II region was explored. High levels of uptake were obtained for both passive and active tumor targeting probes SXH and SDH. Furthermore, high resolution imaging of blood vessels on tumors and the whole body of living mice using H1 NPs for the first time has demonstrated precise NIR-II image-guided sentinel lymph node (SLN) surgery.

Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer.

Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.