Fluorescence imaging in near-infrared IIb (NIR-IIb, 1500-1700 nm) spectrum holds a great promise for tissue imaging. While few inorganic NIR-IIb fluorescent probes have been reported, their organic ...counterparts are still rarely developed, possibly due to the shortage of efficient materials with long emission wavelength. Herein, we propose a molecular design philosophy to explore pure organic NIR-IIb fluorophores by manipulation of the effects of twisted intramolecular charge transfer and aggregation-induced emission at the molecular and morphological levels. An organic fluorescent dye emitting up to 1600 nm with a quantum yield of 11.5% in the NIR-II region is developed. NIR-IIb fluorescence imaging of blood vessels and deeply-located intestinal tract of live mice based on organic dyes is achieved with high clarity and enhanced signal-to-background ratio. We hope this study will inspire further development on the evolution of pure organic NIR-IIb dyes for bio-imaging.
Planar donor and acceptor (D–A) conjugated structures are generally believed to be the standard for architecting highly efficient photothermal theranostic agents, in order to restrict intramolecular ...motions in aggregates (nanoparticles). However, other channels of extra nonradiative decay may be blocked. Now this challenge is addressed by proposing an “abnormal” strategy based on molecular motion in aggregates. Molecular rotors and bulky alkyl chains are grafted to the central D–A core to lower intermolecular interaction. The enhanced molecular motion favors the formation of a dark twisted intramolecular charge transfer state, whose nonradiative decay enhances the photothermal properties. Result shows that small-molecule NIRb14 with long alkyl chains branched at the second carbon exhibits enhanced photothermal properties compared with NIRb6, with short branched chains, and much higher than NIR6, with short linear chains, and the commercial gold nanorods. Both in vitro and in vivo experiments demonstrate that NIRb14 nanoparticles can be used as nanoagents for photoacoustic imaging-guided photothermal therapy. Moreover, charge reversal poly(β-amino ester) makes NIRb14 specifically accumulate at tumor sites. This study thus provides an excited molecular motion approach toward efficient phototheranostic agents.
A particular challenge in the design of organic photosensitizers (PSs) with donor–acceptor (D‐A) structures is that it is based on trial and error rather than specific rules. Now these challenges are ...addressed by proposing two efficient strategies to enhance the photosensitization efficiency: polymerization‐facilitated photosensitization and the D‐A even–odd effect. Conjugated polymers have been found to exhibit a higher 1O2 generation efficiency than their small molecular counterparts. Furthermore, PSs with A‐D‐A structures show enhanced photosensitization efficiency over those with D‐A‐D structures. Theoretical calculations suggest an enhanced intersystem crossing (ISC) efficiency by these strategies. Both in vitro and in vivo experiments demonstrate that the resulting materials can be used as photosensitizers in image‐guided photodynamic anticancer therapy. These guidelines are applicable to other polymers and small molecules to lead to the development of new PSs.
Conjugated polymers have a higher 1O2 generation efficiency than their small molecular counterparts. Photosensitizers with A‐D‐A structures are better than D‐A‐D structures. Both in vitro and in vivo experiments show that the resulting materials can be used as photosensitizers in image‐guided photodynamic anticancer therapy. D=donor, A=acceptor.
Semiconducting polymer nanoparticles (SPNs) emitting in the second near-infrared window (NIR-II, 1000–1700 nm) are promising materials for deep-tissue optical imaging in mammals, but the brightness ...is far from satisfactory. Herein, we developed a molecular design strategy to boost the brightness of NIR-II SPNs: structure planarization and twisting. By integration of the strong absorption coefficient inherited from planar π-conjugated units and high solid-state quantum yield (ΦPL) from twisted motifs into one polymer, a rise in brightness was obtained. The resulting pNIR-4 with both twisted and planar structure displayed improved ΦPL and absorption when compared to the planar polymer pNIR-1 and the twisted polymer pNIR-2. Given the emission tail extending into the NIR-IIa region (1300–1400 nm) of the pNIR-4 nanoparticles, NIR-IIa fluorescence imaging of blood vessels with enhanced clarity was observed. Moreover, a pH-responsive poly(β-amino ester) made pNIR-4 specifically accumulate at tumor sites, allowing NIR-IIa fluorescence image-guided cancer precision resection. This study provides a molecular design strategy for developing highly bright fluorophores.
Aggregation-induced emission (AIE) is a cutting-edge fluorescence technology, giving highly-efficient solid-state photoluminescence. Particularly, AIE luminogens (AIEgens) with emission in the range ...of second near-infrared window (NIR-II, 1000-1700 nm) have displayed salient advantages for biomedical imaging and therapy. However, the molecular design strategy and underlying mechanism for regulating the balance between fluorescence (radiative pathway) and photothermal effect (non-radiative pathway) in these narrow bandgap materials remain obscure. In this review, we outline the latest achievements in the molecular guidelines and photophysical process control for developing highly efficient NIR-II emitters or photothermal agents with aggregation-induced emission (AIE) attributes. We provide insights to optimize fluorescence efficiency by regulating multi-hierarchical structures from single molecules (flexibilization) to molecular aggregates (rigidification). We also discuss the crucial role of intramolecular motions in molecular aggregates for balancing the functions of fluorescence imaging and photothermal therapy. The superiority of the NIR-II region is demonstrated by fluorescence/photoacoustic imaging of blood vessels and the brain as well as photothermal ablation of the tumor. Finally, a summary of the challenges and perspectives of NIR-II AIEgens for
in vivo
theranostics is given.
Structural and process controls of NIR-II AIEgens realize manipulating of radiative (R) and nonradiative (NR) decay for precise theranostics.
Molecules have limited mobility in the solid state because of the strong intermolecular interactions, and therefore, applications based on solid-state molecular motions are seldom explored. Herein, ...by manipulating the solid-state intramolecular motion of tetraphenylethylene (TPE) in a crystallizing polymer matrix, controlled fluorescent patterns with information storage and encoding functionality are developed. The intramolecular mobility of TPE can not only affect the fluorescence intensity but also determine the photocyclization activity, which can be tuned by surrounding polymer rigidity. The soft amorphous region in the semicrystalline polymer facilitates the intramolecular motion to achieve weak blue emission and high photocyclization activity, whereas the rigid crystalline phase restricts the intramolecular motion to give intense blue emission and low photoreactivity. Meanwhile, in the process of crystallization, the dynamic movement of the polymer chain in the crystal growth boundary layer further accelerates the intramolecular motions of TPE, allowing enhanced photoreactivity across crystalline and amorphous regions. The motion-dominated fluorescence allows TPE as a smart molecular robot to generate desired fluorescent patterns triggered by polymer crystallization. Our findings provide a correlation between microscopic molecular motions and macroscopic optical signals.
AIE polymers have been extensively researched in the fields of OLEDs, sensing, and cancer treatment since its first report in 2003, which have achieved numerous breakthroughs during the years. In ...comparison with small molecules, it can simultaneously combine the unique advantages of AIE materials and the polymer itself, to further enhance their corresponding photophysical performances. In this review, we enumerate and discuss the common construction strategies of AIE-active polymers and summarize the progress of research on polymerization enhancing luminescence, photosensitization, and room-temperature phosphorescence (RTP) with their related applications in chemo/bio-sensing and therapy. To conclude, we also discuss current challenges and prospects of the field for future development.
Although organic materials with near infrared (NIR)‐II fluorescence and a photothermal effect have been widely investigated for the accurate diagnosis and treatment of tumors, optimizing the output ...signals of both remain challenging. Here, a strategy by “enlarging absorption reservoir” to address this issue, since an increase in photon absorption can naturally enhance output signals, is proposed. As a proof‐of‐concept, a large π‐conjugated diketopyrrolopyrrole (DPP) unit is selected to fabricate strong light‐absorbing systems. To enhance solid‐state fluorescence, highly twisted alkylthiophene–benzobisthiadiazole–alkylthiophene and triphenylamine rotor are introduced to restrict the strong intermolecular π–π interactions. Moreover, the number of DPP units in molecules is engineered to optimize photophysical properties. Results show that TDADT with two DPP units possesses an exceptionally high molar absorptivity of 2.1 × 105 L mol−1 cm−1 at 808 nm, an acceptable NIR‐II quantum yield of 0.1% (emission peak at 1270 nm), and a sizeable photothermal conversion efficiency of 60.4%. The excellent photophysical properties of the TDADT nanoparticles are particularly suitable for in vivo NIR‐II imaging‐guided cancer surgery and NIR‐I photothermal therapy. The presented strategy provides a new approach of designing highly efficient NIR‐II phototheranostic agents.
A molecular design strategy, enlarging the absorption reservoir, is proposed to enhance fluorescence intensity and photothermal properties through an increase in photon absorption. The resulting molecules are particularly suitable for in vivo near infrared (NIR)‐II imaging‐guided cancer surgery and NIR‐I photothermal therapy in live mice.
Nonpharmacological therapies for Alzheimer's disease (AD) have become a popular research topic, and acoustic stimulation during sleep is one such promising strategy for the clinical treatment of AD. ...Some animal experiments have illustrated that acoustic stimulation at a specific frequency can ameliorate AD-related pathology or improve cognition in mice, but these studies did not explore the effective time window of auditory stimulation. Here, we explored the effects of acoustic stimulation during wakefulness and acoustic stimulation during sleep on cognition and AD-related pathology in APP/PS1 mice and the underlying mechanisms. In this study, forty APP/PS1 mice were equally divided into the following 4 groups and treated for 28 days: the chronic sleep deprivation (CSD) group (exposed to sleep deprivation from zeitgeber time ZT 0 to ZT 12 each day), the normal sleep and stress exposure (NSS) group (exposed to a stressor from ZT 0 to ZT 12 each day), the acoustic stimulation during wakefulness (ASW) group (exposed to sleep deprivation and 40 Hz acoustic stimulation from ZT 0 to ZT 12 each day) and the acoustic stimulation during sleep (ASS) group (exposed to sleep deprivation from ZT 0 to ZT 12 and 40 Hz acoustic stimulation from ZT 12 to ZT 24 each day). After the intervention, cognition was assessed by behavioural experiments. The amyloid-β burden was analysed by Western blotting, immunofluorescence and enzyme-linked immunosorbent assay. Tau pathology was assessed by Western blotting. Mitochondrial function was evaluated by transmission electron microscopy, Western blotting and fluorescence intensity measurement. We found that the NSS and ASS groups had better cognitive functions than the CSD and ASW groups. The Aβ burden and tau phosphorylation were lower in the NSS and ASS groups than in the CSD and ASW groups. Mitochondrial function was better in the NSS and ASS groups than in the CSD and ASW groups. However, the differences in these parameters between the NSS and ASS groups and between the CSD and ASW groups were not significant. Our findings suggest that acoustic stimulation at a specific frequency during sleep, but not during wakefulness, reduces the amyloid-β burden by inhibiting amyloid beta precursor protein-binding protein 2, hinders tau phosphorylation by blocking glycogen synthase kinase 3 beta, and restores mitochondrial function by elevating mitophagy and promoting mitochondrial biogenesis.
•40 Hz acoustic stimulation during sleep reduces the amyloid-β burden.•40 Hz acoustic stimulation during sleep hinders tau phosphorylation.•40 Hz acoustic stimulation during sleep restores mitochondrial function.•40 Hz acoustic stimulation during sleep improves cognition.
Purpose
Sleep disturbances are common in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients. Non-rapid eye movement stage 3 (N3), rapid eye movement stage (REM), spindle density, ...and K-complex (KC) density are decreased in MCI and AD patients. Periodic limb movements in sleep (PLMS) are increased in other neurodegenerative diseases. We aimed to distinguish amnestic mild cognitive impairment (aMCI) patients from the overall population of MCI patients by comparing the N3 and REM proportions, the morphological characteristics of spindles and KCs and the periodic limb movement index (PLMI) among control, aMCI and AD subjects.
Methods
In 92 subjects (30 controls, 32 aMCI and 30 AD), sleep stages, spindles, KCs and PLMS were recorded during the second of two nights of polysomnography (PSG). We compared the above parameters among the three groups.
Results
AD and aMCI subjects had lower proportions of N3 and REM, poorer spindle and KC activities and more frequent PLMS than controls. These alterations were associated with decreased Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. We determined cut-off values for distinguishing aMCI and AD using logistic regression and receiver operating characteristic (ROC) analyses.
Conclusions
AD and aMCI patients have abnormal sleep stage proportions, spindles, KCs and PLMS. The combination of the above alterations may distinguish aMCI and AD patients from controls with high specificity and sensitivity.
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