Ferroptosis regulates cell death through reactive oxygen species (ROS)‐associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with ...no clear evidence. Herein, we report the first example of an LD/nucleus dual‐targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor–acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual‐targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis‐related diseases.
The first lipid droplet (LD)/nucleus dual‐targeted ratiometric fluorescence probe, CQPP, for monitoring polarity change was developed. CQPP offers ratiometric fluorescence and fluorescence lifetime imaging of LD polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model.
Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through ...noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL‐100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3‐azido‐d‐alanine (d‐AzAla). After intravenous injection, MIL‐100 (Fe) NPs can accumulate preferentially and degrade rapidly within the high H2O2 inflammatory environment, releasing d‐AzAla in the process. d‐AzAla is selectively integrated into the cell walls of bacteria, which is confirmed by fluorescence signals from clickable DBCO‐Cy5. Ultrasmall photosensitizer NPs with aggregation‐induced emission characteristics are subsequently designed to react with the modified bacteria through in vivo click chemistry. Through photodynamic therapy, the amount of bacteria on the infected tissue can be significantly reduced. Overall, this study demonstrates the advantages of metal–organic‐framework‐assisted bacteria metabolic labeling strategy for precise bacterial detection and therapy guided by fluorescence imaging.
A novel strategy for in vivo bacterial metabolic labeling and precise antibacterial therapy is developed based on the combination of a metal–organic framework (MOF) as a carrier for amino acid delivery and photosensitizers with aggregation‐induced emission characteristics for imaging and therapy. The formulated MOF‐assisted strategy represents a promising alternative to antibiotics in image‐guided antibacterial therapy.
Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular ...probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy.
The nucleus is considered the ideal target for anti‐tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear ...target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear‐targeted material MeTPAE with aggregation‐induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton. MeTPAE can not only interact with histone deacetylases (HDACs) to inhibit cell proliferation but also damage telomere and nucleic acids precisely through photodynamic treatment (PDT). The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent PDT anti‐tumor activity, which offered new opportunities for the effective treatment of malignant tumors.
A nuclear‐targeted material MeTPAE with AIE characteristics was developed. MeTPAE can not only interact with HDACs to inhibit cell proliferation, but also damage telomere and nucleic acids precisely through photodynamic treatment. The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent photodynamic therapy (PDT) anti‐tumor activity, which offered new opportunities for the effective treatment of malignant tumors.
We demonstrate that the incorporation of one or two amino acids of phenylalanine (F) or 4‐fluoro phenylalanine (fF) will greatly lower the background fluorescence intensities of conventional quenched ...probes with quenchers. This enhanced quenching effect was due to the synergetic effect of the aggregation caused quenching and the presence of a quencher. Such strategy will not greatly affect the enzyme recognition properties to the probes. We also demonstrated that our self‐assembled nanoprobe with the enhanced quenching effect showed a better performance in cells for the detection of cell apoptosis than the unassembled probes. Our study demonstrates that using molecular self‐assembly can optimize and improve the performance of molecular probes and it provides a simple but very useful strategy to boost the signal‐to‐noise ratios of fluorescence probes.
The incorporation of one or two fluoro phenylalanine groups (fFs) in conventional quenched probes can lead to the production of self‐assembled probes with enhanced quenching effects. The self‐assembled probes possess similar enzyme recognition and fluorescence recovery properties. This provides a useful strategy for the design of molecular probes with good fluorescence turn‐on properties.
A new bottom‐up nanocrystallization method is developed to fabricate highly fluorescent organic nanocrystals in aqueous media using an aggregation‐induced emission fluorogen (AIEgen) as an example. ...The nanocrystallization strategy leads to the fabrication of uniform nanocrystals of 110 ± 10 nm size in aqueous media, which shows over 400% increase in brightness as compared to the amorphous nanoaggregates.
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Islet transplantation is considered the most promising therapeutic option with the potential to cure diabetes. However, efficacy of current clinical islet transplantation is limited ...by long-term graft dysfunction and attrition. We have investigated the therapeutic potential of a silk fibroin macroporous (SF) scaffold for syngeneic islet transplantation in diabetic mice. The SF scaffold was prepared via lyophilisation, which enables incorporation of active compounds including cytokines, peptide and growth factors without compromising their biological activity. For the present study, a heparin-releasing SF scaffold (H-SF) in order to evaluate the versatility of the SF scaffold for biological functionalisation. Islets were then co-transplanted with H-SF or SF scaffolds in the epididymal fat pad of diabetic mice. Mice from both H-SF and SF groups achieved 100% euglycaemia, which was maintained for 1year. More importantly, the H-SF-islets co-transplantation led to more rapid reversal of hyperglycaemia, complete normalisation of glucose responsiveness and lower long-term blood glucose levels. This superior transplantation outcome is attributable to H-SF-facilitated islet revascularisation and cell proliferation since significant increase of islet endocrine and endothelial cells proliferation was shown in grafts retrieved from H-SF-islets co-transplanted mice. Better intra-islet vascular reformation was also evident, accompanied by VEGF upregulation. In addition, when H-SF was co-transplanted with islets extracted from vegfr2-luc transgenic mice in vivo, sustained elevation of bioluminescent signal that corresponds to vegfr2 expression was collected, implicating a role of heparin-dependent activation of endogenous VEGF/VEGFR2 pathway in promoting islet revascularisation and proliferation. In summary, the SF scaffolds provide an open platform as scaffold development for islet transplantation. Furthermore, given the pro-angiogenic, pro-survival and minimal post-transplantation inflammatory reactions of H-SF, our data also support the feasibility of clinical implementation of H-SF to improve islet transplantation outcome.
1) The silk fibroin scaffold presented in the present study provides an open platform for scaffold development in islet transplantation, with heparinisation as an example.
2) Both heparin and silk fibroin have been used clinically. The excellent in vivo therapeutic outcome reported here may therefore be clinically relevant and provide valuable insights for bench to bed translation.
3) Compared to conventional clinical islet transplantation, during which islets are injected via the hepatic portal vein, the physical/mechanical properties of silk fibroin scaffolds create a more accessible transplantation site (i.e., within fat pad), which significantly reduces discomfort.
4) Islet implantation into the fat pad also avoids an instant blood mediated inflammatory response, which occurs upon contact of islet with recipient’s blood during intraportal injection, and prolongs survival and function of implanted islets.
Abstract The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to ...Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O 2 –• ). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O 2 to O 2 –• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.
Two new megastigmane glycosides, (6 R,7E,9R)-3-oxo-α-ionyl-9-O-α-L-rhamnopyranosyl-(1''→4')-β-D-glucopyranoside (1) and (6 R,7E,9R)-3-oxo-α-ionyl-9-O-β-D-glucopyranosyl-(1''→6')-β-D-glucopyranoside ...(2), together with six known analogues (3-8) were isolated from the leaves of Nicotiana tabacum. The structures of all metabolites were determined by comprehensive analysis of NMR and MS spectroscopic data as well as by comparison with those of previously reported. The in vitro anti-inflammatory activity of all isolates was evaluated using a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model, and the compounds 1, 3, 7, and 8 exhibited inhibition of LPS-induced NO production in RAW264.7 macrophage cells with IC50 values of 42.3-61.7 μM (positive control, dexamethasone, IC50 = 21.3 ± 1.2 μM).
The
flower is widely used in China and Japan as a food, beverage, and medicine for many diseases. In our work, two new caffeoylquinic acid derivatives (
), a new flavanone glycoside (
), and six ...reported flavanones (
⁻
) were isolated and identified from the flowers of
. The chemical structures of all isolates were elucidated by the analysis of comprehensive spectroscopic data as well as by comparison with previously reported data. The isolated constituents
⁻
were evaluated for their neuroprotective activity, and compounds
and
displayed neuroprotective effects against hydrogen peroxide-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.
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