Phototheranostics have emerged and flourished as a promising pattern for cancer theranostics owing to their precise photoinduced diagnosis and therapeutic to meet the demands of precision medicine. ...The diagnosis information and therapeutic effect are directly determined by the fluorescence imaging ability and photothermal conversion efficiency (PCE) of phototheranostic agents. Hence, how to balance the competitive radiative and nonradiative processes of phototheranostic agents is the key factor to evaluate the phototheranostic effect. Herein, molecules named ICRs with high photostaibility are rationally designed, exhibiting fluorescence emission in the second near‐infrared window (NIR‐II, 1000–1700 nm) and high PCE, which are related to the strong donor–acceptor (D–A) interaction and high reorganization energy Noteworthily, ICR‐Qu with stronger D–A interaction and a large‐sized conjugated unit encapsulated in nanoparticles exhibits high PCE (81.1%). In addition, ICR‐QuNPs are used for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to guide deep‐tissue photonic hyperthermia, achieving precise removal and inhibition of breast cancer. Furthermore, combined with α‐PD‐1, ICR‐QuNPs show huge potential to be a facile and efficient tool for photo‐immunotherapy. More importantly, this study not only reports an “all‐in‐one” polymethine‐based phototheranostic agent, but also sheds light on the exploration of versatile organic molecules for future practical applications.
Polymethine dyes with second near‐infrared emission and photoacoustic imaging capability are synthesized by the electronic‐donor group regulation strategy, which demonstrates high photothermal conversion efficiency (PCE = 81.1%) as an antitumor stategy in vivo and in vitro under the multimodal imaging guidance; theoretical calculation reveals the structure regulation mechanism for the polymethine‐based phototheranostic agent to achieve an excellent PCE.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The efficient generation of reactive oxygen species (ROS) is crucial for the photodynamic therapy (PDT) effect. The D‐π‐A molecular engineering strategy can effectively separate the highest occupied ...molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) distribution to achieve a smaller energy gap thereby facilitating ROS generation of photosensitizers (PSs). Incorporating heterocycles as π‐bridges can not only extend the conjugation system with improving the degree of π‐delocalization but also effectively accelerate the intersystem crossing process. Herein, a N‐heterocycle purine is innovatively integrated into the D‐π‐A structure as a π‐bridge, which significantly enhances the photodynamic performance by achieving high levels of Type I and Type II ROS generation. The most potent TPM‐QN2 is obtained by modulating the electron‐withdrawing ability of the acceptor (quinolinium), with a 1O2 yield of 9.32, which is the highest yield reported to date. Furthermore, these purine‐based PSs exhibit excellent capabilities in promoting cell photodynamic ablation and inhibiting tumor tissue growth. This novel approach of introducing natural heterocycles provides a promising avenue for developing high‐performance PSs and promoting tumor phototherapy.
Photosensitizers with D‐π‐A structures are constructed for photodynamic anti‐tumor therapy by using multi‐N heterocycle (purine) as π‐bridges, which enhances D‐π‐A strength and extends the π‐conjugation system, thus facilitating the intersysterm crossing process and realizing an excellent Type I and Type II reactive oxygen species generation efficiency.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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
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
The binding mechanism between pefloxacin mesylate (PM) and transferrin (Tf) was explored using spectral experiment combined with molecular modeling techniques. The binding parameters and ...thermodynamic functions of PM-Tf solution system were measured at different temperatures. The effect of PM on molecular conformation of Tf was investigated and the interaction mechanism was also discussed. The results showed that dynamic quenching mechanism occurs with PM binding to Tf. The value of binding distances (r) is low, which indicates the occurrence of energy transfer. The drug had conformational effect on Tf, which resulted in changes of hydrophobic environment of the binding domain in Tf. According to the obtained thermodynamic parameters, the main interaction force between PM and Tf is attributed to hydrophobic bonding. The results of molecular modeling revealed that hydrophobic and hydrogen bonds are main binding forces in the PM-Tf system. These results were in accordance with spectral experiments. The research
Drug toxicity and related drug-induced liver injury (DILI) have become major biosafety issues. Enzyme-activated fluorescent probes have been demonstrated as a powerful tool for the diagnosis of DILI; ...however, they suffer from diffusive signal dilution and interference with other organs, thus leading to misassessment of drug toxicity and inaccurate diagnosis. Alkaline phosphatase (ALP) is an important biomarker, and alterations in the enzyme level are tightly correlated to the severity of liver damage. Herein, an enzyme-activated intramolecular hydrogen bond (IMHB) enhanced probe (TPEG-P) was developed for ALP detection in cells and mice models of DILI. Differing from previously reported intermolecular charge transfer (ICT) or the excited-state intramolecular proton transfer (ESIPT) mechanisms, the TPEG-P enables precise recognition and imaging of ALP only through the activation of intramolecular hydrogen bonds and could in situ sensitively detect varying degrees of liver injury caused by drug toxicity. This IMHB strategy will advance the development of enzyme-activated probes and precise bioimaging in the future.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from ...postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.
A new skeleton bisabolane-type sesquiterpene curcuminoid,bisabocurcumin（1）,along with 5 known compounds,curcumin（2）, ...demethoxycurcumin（3）,bidemethoxycurcumin（4）,（1E,4E）-1,5-bis（4-hydroxy-3-methoxyphenyl）-penta-1,4-dien-3-one（5）,and （1E,4E）-1-（4-hydroxy-3-methoxyphenyl）-5-（4-hydroxy phenyl-）-penta-1,4-dien-3-one（6）were isolated from the rhizomes of Curcuma longa L.Their structures were determined on the basis of spectroscopic analysis.Bisabocurcumin（1） is firstly obtained from nature with a new skeleton combined by a bisabolane-type sesquiterpene and a 1,7-diphenylheptanoid through a C-C bond.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after ...traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.
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