Organic molecules with second near‐infrared (NIR‐II, 1000–1700 nm) emission have significant advantages over NIR‐I (600–900 nm) dyes, and have been widely used as phototheranostic agents (PTAs) and ...fluorescent probes. However, the two biggest challenges for such reagents are improving photothermal conversion efficiency (PCE), and simplifying tedious synthetic procedures. Herein, different from the traditional NIR skeleton, for the first time, it develops two novel dibenzofulvene‐based NIR‐II emission PTAs via D‐π‐A concept with high PCEs through two simple synthetic steps. The increased intramolecular charge transfer effect and extended π‐conjugation effectively red‐shift their emissions to the NIR‐II region. In addition, the introduction of molecular rotors/vibrators and the formation of π–π stacking prompt the two PTAs to exhibit high PCEs. Notably, FE‐IDMN nanoparticles (FE‐IDMN NPs) achieve an exciting PCE of 82.6%, higher than most reported photothermal agents with NIR‐II emission. FE‐IDMN NPs also possess good colloidal, pH, and photothermal stabilities, as well as excellent photoacoustic response, which is further successfully applied for NIR‐II fluorescence/photoacoustic/photothermal imaging‐guided photothermal therapy. This work provides a simple strategy for constructing new D‐π‐A PTAs with low molecular weight, NIR‐II emission, and high PCE for cancer therapy.
A novel low‐molecular‐weight dibenzofulvene‐based D‐π‐A phototheranostic agent (PTA) with NIR‐II emission and high PCE is developed by the strategies of enhancing D‐A strength, introducing molecular rotors/vibrators, and facilitating intermolecular π–π stacking. The PTA is successfully applied in the multi‐modal imaging (NIR‐II fluorescence/photoacoustic/photothermal imaging)‐guided photothermal therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The abnormal microenvironment parameter, viscosity, is closely connected with various diffusion processes, signal transduction, molecule interactions, and various diseases. It is greatly significant ...to design viscosity-dependent near-infrared (NIR) small molecule fluorescence probes for visualizing biological processes or diagnosing diseases. Herein, through the stepwise modulating structure of the silicon–rhodamine fluorophore (SR), we report three viscosity probes with allyl or methyl group as rotors, named SR-T-Al, SR-S-Al, and SR-T-Me. Among them, SR-T-Al demonstrates better viscosity responsibility from 1.0 to 1410.4 cP of viscosity. Therefore, the probe of SR-T-Al is successfully applied to sensitively monitor lysosome microscopic viscosity changes of living cells induced by oxygen stress. What’s more, based on its advantages in NIR emission (669 nm) and large Stokes shift (201 nm), we also use it to image variations of viscosity in an acute hepatitis mouse induced by carbon tetrachloride. Both time and concentration-dependent induction models display the great ability of SR-T-Al to detect viscosity alteration. All the experimental results indicated that this allyl-rotor-based NIR viscosity probe could provide a general platform to monitor abnormal physiological processes and diseases relating to viscosity.
Enriching the palette of high-performance fluorescent dyes is vital to support the frontier of biomedical imaging. Although various rhodamine skeletons remain the premier type of small-molecule ...fluorophores due to the apparent high brightness and flexible modifiability, they still suffer from the inherent defect of small Stokes shift due to the nonideal fluorescence imaging signal-to-background ratio. Especially, the rising class of fluorescent dyes, sulfone-substituted xanthone, exhibits great potential, but low chemical stability is also pointed out as the problem. Molecular engineering of sulfone-xanthone to obtain a large Stokes shift and high stability is highly desired, but it is still scarce. Herein, we present the combination modification method for optimizing the performance of sulfone-xanthone. These redesigned fluorescent skeletons owned greatly improved stability and Stokes shift compared with the parent sulfone-rhodamine. To the proof of bioimaging capacity, annexin protein-targeted peptide LS301 was introduced to the most promising dyes, J-S-ARh, to form the tumor-targeted fluorescent probe, J-S-LS301. The resulting probe, J-S-LS301, can be an outstanding fluorescence tool for the orthotopic transplantation tumor model of hepatocellular carcinoma imaging and on-site pathological analysis. In summary, the combination method could serve as a basis for rational optimization of sulfone-xanthone. Overall, the chemistry reported here broadens the scope of accessible sulfone-xanthone functionality and, in turn, enables to facilitate the translation of biomedical research toward the clinical domain.
Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based ...fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.
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IJS, KILJ, NUK, PNG, UL, UM
Herein, we constructed a novel aminofluorene-based fluorescence probe (
FEN-CE
) for the detection of carboxylesterase (CE) in living cells by a ratiometric near-infrared (NIR) fluorescence signal.
...FEN-CE
with NIR emission (650 nm) could be hydrolyzed specifically by CE and transformed to FENH with the release of the self-immolative group, which exhibited a red-shifted emission peak of 680 nm. In addition,
FEN-CE
showed high selectivity for CE and was successfully used in the detection of CE activity in living cells through its ratiometric NIR fluorescence signals.
Herein, we constructed a novel aminofluorene-based fluorescence probe (
FEN-CE
) for the detection of carboxylesterase (CE) in living cells by a ratiometric near-infrared (NIR) fluorescence signal.
Ras plays a pivotal role in many cellular activities, and its subcellular compartmentalization provides spatial and temporal selectivity. Here we report a mode of spatial regulation of Ras signaling ...in the Golgi apparatus by two highly homologous proteins PAQR10 and PAQRll of the progestin and AdipoQ receptors family. PAQRI0 and PAQRll are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQRll stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent man- ner. Overexpression of PAQR10/PAQRll markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQRll can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQRll is in an active state. Consistently, knockdown of PAQR10 and PAQRll reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQRll are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with PAQR10/PAQRll. The simulation of ERK phosphorylation by overexpressed PAQR10/ PAQRll is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQRll. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQRll.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
For the metal-catalyzed asymmetric hydrogenation of α-substituted ketones,
cis
reductive products are generally obtained due to steric hindrance of substituents. Herein, an unprecedented
trans
...reductive products were observed in palladium-catalyzed hydrogenative desymmetrization of cyclic and acyclic 1,3-diketones, providing the chiral
trans
β-hydroxy ketones with two adjacent stereocenters including one α-tertiary or quaternary stereocenter with high enantioselectivity and diastereoselectivity. Mechanistic studies and DFT calculations suggested that the rarely observed diastereoselectivity reversal is ascribed to the charge-charge interaction between the palladium and aromatic ring of the substrate, which could not only result in the reversal of the diastereoselectivity, but also improve the reactivity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background Previous prognosis analyses of colorectal cancer （CRC） patients with stage Ⅱ and Ⅲ disease were done as separate categories. The purpose of this study was to analyze prognostic factors ...associated with survival in a group of patients who underwent radical resection of stages Ⅱ and Ⅲ CRC.Methods A retrospective review was performed for 141 consecutive stages Ⅱ and Ⅲ patients who had undergone radical resection of coloractal adenocarcinoma between May 2003 and November 2003. Univariate and multivariate analyses were performed to assess the effect of record variables on disease free survival and overall survival.Results The median follow-up time was 59 months, and the 3-and 5-year survival rates were 76% and 68%,respectively. Four factors were independently associated with a worse disease-free survival： diabetes （hazard ratio （HR） 2.338; 95% confidence interval （CI） 1.011-5.407）, expression of cyclooxygenase-2 （Cox-2） （HR 0.335; 95% CI 0.126-0.888）, expression of matrix metalloproteinases 2 （MMP-2） （FIR 0.233; 95% CI 0.101-0.541）, expression of vascular endothelial growth factor （VEGF） （HR 0.295; 95% CI 0.088-0.996）. Four factors were independently associated with a worse overall survival： lymph nodes metastasis （HR 1.67; 95% CI 1.29-2.14）, Cox-2 positive （HR 0.056; 95% CI 0.247-0.731）, MMP-2 positive （HR 0.398; 95% CI 0.190-0.836）, VEGF （HR 0.364; 95% CI 0.090-0.716）.Conclusions Diabetes, expression of Cox-2, MMP-2 and VEGF were independently associated with a worse diseasefree survival. Lymph nodes metastasis, expression of Cox-2, MMP-2 and high level of VEGF predicted a poor overall survival.
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