Publications by authors named "Kehua Xu"

Although photothermal therapy (PTT) has been widely applied for tumor treatment, tumor cells thermotolerance still limits PTT efficiency. Since the overexpressed HSP90α in tumor cells further enhances thermotolerance and protects them from PTT damage, a new nanoprobe that can specifically detect and downregulate HSP90α mRNA was developed to enhance the PTT effect. Based on the HSP90α mRNA sequence, the nanoprobe Au-DNA1/DNA2 can specifically bind to HSP90α mRNA for recovering its fluorescence and further inhibit the synthesis of HSP90α to reduce tumor heat tolerance.

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Resveratrol has been garnering considerable attention as a promising chemopreventive and chemotherapeutic drug against metastatic tumors such as triple-negative breast cancer (TNBC). However, the potential application of resveratrol has been highly limited due to its poor solubility, rapid conjugation, low bioavailability, and bioactivity. In this study, a silica mesoporous nanoparticle (MSN)-based drug delivery system (DDS), named Au-Se@MSN, is developed to deliver the loaded resveratrol, endowing it with properties of targeted delivery, excellent bioavailability, and antioxidation of resveratrol.

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A pH-responsive cascade nanoplatform based on ZIF-8 disintegrates in the weakly acidic tumor microenvironment to release MnO, CaO and Ce6. The drugs can cyclically generate O for sonodynamic therapy, consume glutathione to tune the redox hemostasis, and produce cytotoxic ˙OH to kill tumor cells chemical dynamics therapy.

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Article Synopsis
  • Thoracic aortic aneurysm (TAA) is a serious condition characterized by the dilation of the aorta, leading to potentially life-threatening complications, and there is a lack of effective treatment options.
  • A new three-dimensional microphysiological model was developed using human aortic smooth muscle cells to study TAA and test drugs, revealing important biological features that mimic the disease state more accurately than traditional methods.
  • The study found that the diabetes medication metformin showed promise in restoring normal cell function and improving aortic health in TAA, supporting the use of the microphysiological model for future drug discovery and personalized treatment.
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The detection of prostate specific antigen (PSA) in serum can realize early diagnosis of prostate cancer and prevent the occurrence of prostate tumors, as well as offering guidance during the therapy. Herein, a Au-Se bonded nanoprobes that can specifically detect PSA was designed and constructed. The peptide chains that can be specifically cleaved by PSA were firstly functionalized with fluorescent dye and selenol, and then bind to the Au nanoparticles to produce the probe.

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A novel viscosity probe (NV1) was developed for assessing cancer cell migration. NV1 can respond to changes of viscosity rapidly and exhibits high sensitivity in HepG2 cells treated with starvation, rotenone and nystatin. Importantly, NV1 was used for the first time to evaluate the relationship between intracellular viscosity changes and cancer cell migration and proved that increased intracellular viscosity inhibits cell migration while decreased intracellular viscosity promotes cell migration.

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Lipid droplets (LDs) are involved in various physiological processes and associated with cancer development, and are regarded as a potential tumor marker for cancer diagnosis. Monitoring LDs is of prior importance to understand their involvement in biological mechanisms and the early detection of cancers. Highly sensitive and specific noninvasive fluorescent probes are particularly desirable for imaging LDs and cancer diagnosis.

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A novel dual-aptamer activated proximity-induced qPCR assay was developed for the quantitative analysis of exosomal PD-L1 on T cell-exosome complexes in blood samples.

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Tumor-targeting gold nanorods (AuNRs) assembled through Au-S bonds have been widely used for photothermal therapy (PTT) intravenous injection. However, with extended circulation times, biothiols can replace some S-modified targeting ligands on the surface of the AuNRs, which lowers their targeting efficacy towards cancer cells, resulting in a non-ideal PTT effect. To address this problem, herein, we utilized Se-modified AuNRs to establish a dual functional nanoprobe (Casp-RGD-Se-AuNRs) for improving the therapeutic effect and real-time monitoring of Caspase-9 levels to indicate the degree of cell apoptosis.

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Background: Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. Insufficiency of NOTCH1 expression is highly related to BAV-TAA, but the underlying mechanism remains to be clarified.

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Pyroptosis is closely related to inhibiting the occurrence and development of tumors. However, the pyroptosis pathways (PPs) impacted by different stimulants are still unknown. To accurately understand the PP in cancer cells, we designed a multicolor fluorescent nanoprobe (Cas-NP) to monitor the activation of caspases-1/3/4 during pyroptosis.

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Background: Bicuspid aortic valve (BAV) is the most common congenital heart anomaly and is prone to cause complications, such as valvular stenosis and thoracic aortic dilation. There is currently no reliable way to predict the progression rate to thoracic aortic aneurysm. Here, we aimed to characterize the proteomic landscape in the plasma of stenotic BAV patients and provide potential biomarkers to predict progressive aortic dilation.

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Correction for 'A "double-locked" probe for the detection of hydrogen sulfide in a viscous system' by Fanpeng Kong et al., Chem. Commun.

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As an important cell organelle, the mitochondrion has special viscosities, while abnormal mitochondrial viscosity is closely related to many diseases. Hydrogen peroxide (HO) is an active molecule related to the cell microenvironment, and its influence on mitochondrial viscosity is still not clear, so further investigation is needed. In addition, since excessive accumulation of heavy metal ions would lead to cells' dysfunction, the study of effect of excessive heavy metal ions on mitochondrial viscosity has not been reported.

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Hypochlorous acid (HOCl), as an important reactive oxygen species (ROS), plays an important role in various pathological and physiological processes. Therefore, it is of great significance to identify and detect HOCl in organisms. Herein, a mitochondria-targeting near-Infrared fluorescent probe (CVS) has been designed and synthesized for sensing HOCl.

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Myocardial dysfunction caused by cardiomyocyte apoptosis under ischemic and hypoxic conditions is the pathological basis of most cardiovascular diseases. Current diagnosis of myocardial dysfunction still focuses on the symptomatic stage, usually after the occurrence of the irreversible remodelling and functional impairment. Thus, early stage identification of the apoptotic cardiomyocytes induced by hypoxia is highly significant for preventing the onset and delaying the progression of myocardial dysfunction.

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Nowadays, it still remains a great challenge to develop a simple, fast, and low-toxic method for identification and separation of proteins from complex biological systems. Herein, a nanocomposite (FeO@Au-Se-peptide) was designed and synthesized to fish out methionine-containing proteins based on a non-enzymatic biochemical reaction, which couples amino groups of lysine with the -methyl group of methionine in the presence of HOBr. Peptides which contain four lysine residues (Lys-Lys-Lys-Lys-{Se-Cys}) linked to the FeO@Au nanocomposites were used to capture methionine residues efficiently a S═N cross-linking.

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The expression levels of matrix metalloproteinases (MMPs) are closely related to the degree of inflammation which facilitates tumor cells' invasion and migration. A tricolor fluorescence nanoprobe based on high-fidelity gold-selenium (Au-Se) nanoplatform was designed and constructed for simultaneously imaging matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) to thoroughly investigate the tumor cells' invasion and migration behaviors under inflammation environment. The nanoprobe was assembled by attaching Au NPs with three different peptide substrates respectively labeled with fluorescein isothiocyanate (FITC), 5-carboxytetramethylrhodamine (5-TAMRA) and cyanine 5 (Cy5) via the Au-Se bond.

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The anticancer mechanism for reduced/oxidized ascorbic acid (AA/DHA) is of great significance for clinical cancer therapies. A pH controlled fluorescent nanocarrier was designed to targetably deliver AA and DHA into tumor cells for investigating their function in inducing intracellular apoptosis pathways. A fluorescent silicon nanoparticle with polymer coating serves as the pH controlled nanocarrier to deliver AA or DHA into HepG2 and B16-F10 cells for studying their biological functions.

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Sodium selenite has alleviating effects on liver fibrosis; however, its therapeutic molecular mechanism remains unclear. Herein, hydrogen selenide, a major metabolite of NaSeO, was tested to uncouple the sulfilimine bond in collagen IV, the biomarker of liver fibrosis. A mouse model of liver fibrosis was constructed via a CCl-induced method, followed by the administration of 0.

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Background: Tumor recurrence in patients after surgery severely reduces the survival rate of surgical patients. Targeting and killing recurrent tumor cells and tissues is extremely important for the cancer treatment.

Results: Herein, we designed a nano-biomimetic photothermal-controlled drug-loading platform HepM-TSL with good targeting ability and immunocompatibility for the treatment of recurrent hepatocellular carcinoma.

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We have, for the first time, developed a Au-Se-DNA nanoprobe by upgrading the conventional Au-S bonds of nano-flares to more stable Au-Se bonds for high-fidelity imaging of target RNAs in living cells. The design concept is potentially introduced into various Au-DNA nanosensors that offer wide application prospects in research and clinical practice.

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Reductive stress, the opposite of oxidative stress, represents a disorder in the redox balance state which is harmful to biological systems. For decades, the role of oxidative stress in tumor therapy has been the focus of attention, while the effects of reductive stress have been rarely studied. Here, we report the anti-cancer effects of reductive stress induced by three natural antioxidants (resveratrol, curcumin and celastrol).

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Urokinase-type plasminogen activator (uPA) has been shown to activate matrix metalloproteinase-2 (MMP-2) that leads to the migration and invasion of breast cancer cells. Overexpressed uPA and MMP-2 are regarded as signs of malignant tumors in clinical practice. Therefore, real-time monitoring of the sequential activation of these two signal molecules may have important implications for the evaluation of the invasive potential and tumor progression of breast cancer.

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