Zinc sulfide nanoparticles serve as gas slow-release bioreactors for H2S therapy of ischemic stroke.

Stroke is one of the leading causes of death and disability in the world. Ischemic stroke causes overproduction of reactive oxygen/nitrogen species (RONS) after reperfusion, triggering inflammatory responses that further leads to cell damage. In order to develop novel neuroprotective materials, we synthesized zinc sulfide nanoparticles (ZnS NPs) to function as gas slow-release bioreactors, showcasing stable and sustained H2S release while effectively removing RONS. In cultured cells, ZnS NPs can reduce the oxidative damage caused by oxygen-glucose deprivation and reoxygenation (OGD/R), promote the expression of p-AMPK, enhance microglia M2 polarization, decrease inflammatory factors and reduce neuronal apoptosis. Additionally, it increases the proliferation and migration of endothelial cells, promoting the formation of new neurovascular units by regulating the protein of p-AKT. In mice with ischemic stroke induced by middle cerebral artery occlusion/reperfusion (MCAO/R), ZnS NPs significantly reduce the infarct area and restore the mobility of mice owing to the slow release of H2S. In summary, our results indicate that ZnS NPs can be used as H2S slow-release bioreactors, offering a potentially innovative approach to treat ischemia-reperfusion injury caused by stroke.

Titanium Sulfide Nanosheets Serve as Cascade Bioreactors for H2 S-Mediated Programmed Gas-Sonodynamic Cancer Therapy.

Gas-mediated sonodynamic therapy (SDT) has the potential to become an effective strategy to improve the therapeutic outcome and survival rate of cancer patients. Herein, titanium sulfide nanosheets (TiSX NSs) are prepared as cascade bioreactors for sequential gas-sonodynamic cancer therapy. TiSX NSs themselves as hydrogen sulfide (H2 S) donors can burst release H2 S gas. Following H2 S generation, TiSX NSs are gradually degraded to become S-defective and partly oxidized into TiOX on their surface, which endows TiSX NSs with high sonodynamic properties under ultrasound (US) irradiation. In vitro and in vivo experiments show the excellent therapeutic effects of TiSX NSs. In detail, large amounts of H2 S gas and reactive oxygen species (ROS) can simultaneously inhibit mitochondrial respiration and ATP synthesis, leading to cancer cell apoptosis. Of note, H2 S gas also plays important roles in modulating and activating the immune system to effectively inhibit pulmonary metastasis. Finally, the metabolizable TiSX NSs are excreted out of the body without inducing any significant long-term toxicity. Collectively, this work establishes a cascade bioreactor of TiSX NSs with satisfactory H2 S release ability and excellent ROS generation properties under US irradiation for programmed gas-sonodynamic cancer therapy.

Titanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) has attracted widespread interest in biomedicine, owing to its novel and noninvasive therapeutic method triggered by ultrasound (US). Herein, the Ti3C2 MXene nanosheets (Ti3C2 NSs) are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment. With the high-temperature treatment, the oxygen defect of Ti3C2 MXene nanosheets (H-Ti3C2 NSs) is greatly increased. Therefore, the electron (e-) and hole (h+) generated by US can be separated faster due to the improved degree of oxidation, and then the recombination of e--h+ can be prevented with the abundant oxygen defect under US irradiation, which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti3C2 NSs without high-temperature treatment. After PEGylation, the H-Ti3C2-PEG NSs show good stability and biocompatibility. In vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H-Ti3C2-PEG NSs, which can improve the SDT efficacy. In vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment, showing photothermal therapy (PTT) enhanced SDT. Most importantly, the H-Ti3C2-PEG NSs can be biodegraded and excreted out of the body, showing no significant long-term toxicity. Our work develops the defective H-Ti3C2 NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer, extending the biomedical application of MXene-based nanoplatforms.

A novel gold nanoparticles decorated magnetic microbead-based molecular beacon for DNA multiplexing detection by flow cytometry.

Gold nanoparticles-based molecular beacon (Au NPs-MB), due to its extraordinary highly-quenching efficiency for fluorophores, has been extensively investigated and widely used for bioimaging and bioassay. However, apart from irreversible aggregation during the "aging" step, the preparation of Au NPs-MB often suffers from relatively poor salt stability, limiting its further in vivo application. Herein, Au NPs decorated magnetic microbeads was developed to construct a novel magnetic MB for DNA assay, which not only totally solved the aggregation problem of Au NPs, but also exhibited robust stability in buffer solution. Most importantly, the fluorescence signal of each microbeads could be collected individually, realizing single microbeads-based DNA imaging, and the detection limit for target DNA could reach 0.1 nM with the detection range of 0.2-20 nM. More importantly, because the magnetic microbeads with three sizes could be readily distinguished by flow cytometry, the employed three types of hairpin DNA probes can be labelled with the same dye FITC without fluorescence cross-interference. Therefore, multiplexing detection of tumor-suppressor genes (p16, p21 and p53) could be readily realized by using size-encoded magnetic microbeads pre-functionalized with corresponding probe DNA illustrating the potential of this method in multiplexing bioassay applications.

Single microbead-based fluorescence "turn on" detection of biothiols by flow cytometry.

Biological thiols (biothiols), such as glutathione (GSH), cysteine (Cys) and homocysteine (Hcy), play a vital role in the process of reversible redox reactions in physiological systems. In this work, flow cytometry-based fluorescent sensor is for the first time developed for the detection of biothiols in a fluorescence "turn on" manner. The probe which we name "Polystyrene/Quantum Dots/Gold Nanoparticles" or (PS/QDs/Au) is constructed by immobilizing QDs onto the surface of PS microbeads to obtain fluorescent microbeads. The probe (PS/QDs/Au) is constructed by immobilizing QDs onto the surface of PS microbeads to obtain fluorescent microbeads, followed by gold NPs absorption through electrostatic interaction to quench their fluorescence. In the presence of biothiols, the fluorescence of our probe can be restored in less than 5 min, and the detection limits for GSH, Cys and Hcy are 0.5 µM, 0.1 µM and 0.3 µM, respectively. Most importantly, the fluorescence signal of each of our probe microbeads can be collected individually by flow cytometry, realizing single microbead-based biothiols detection for the first time. Moreover, the probe is successfully applied to imaging of intracellular biothiols in A549 cells, demonstrating its potential in biological application.

Multifunctional Two-Dimensional Core-Shell MXene@Gold Nanocomposites for Enhanced Photo-Radio Combined Therapy in the Second Biological Window.

Multifunctional nanoplatforms with special advantages in the diagnosis and treatment of cancer have been widely explored in nanomedicine. Herein, we synthesize two-dimensional core-shell nanocomposites (Ti3C2@Au) via a seed-growth method starting from the titanium carbide (Ti3C2) nanosheets, a classical type of MXene nanostructure. After growing gold on the surface of Ti3C2 nanosheets, the stability and biocompatibility of the nanocomposites are greatly improved by the thiol modification. Also importantly, the optical absorption in the near-infrared region is enhanced. Utilizing the ability of the high optical absorbance and strong X-ray attenuation, the synthesized Ti3C2@Au nanocomposites are used for photoacoustic and computed tomography dual-modal imaging. Importantly, the mild photothermal effect of the Ti3C2@Au nanocomposites could improve the tumor oxygenation, which significantly enhances the radiotherapy. No obvious long-term toxicity of the nanocomposites is found at the injected dose. This work highlights the promise of special properties of MXene-based multifunctional nanostructures for cancer theranostics.

Transdermal delivery of praziquantel: effects of solvents on permeation across rabbit skin.

To explore a new method for the transdermal delivery of praziquantel (PZQ), the effects of solvents on permeation across rabbit skin were investigated. The solubility of PZQ in five different solvents, ethylene glycol monophenyl ether (EGPE), 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, and oleic acid, were measured with a UV-Vis spectrophotometer. The determination of the n-octanol/water partition coefficient of PZQ in the five different solutions and assay of serum concentration following PZQ transdermal administration in rabbits were performed using HPLC. The results indicated that the transdermal absorption of the drug was related to the partition coefficient and lipophilic characteristics of the solvent. The optimal solvent for PZQ transdermal delivery was EGPE in our protocol. The solubility of PZQ in EGPE is >400 mg/ml, and the apparent partition coefficient of PZQ in the solution is 0.895 (log P value). After transdermal administration of PZQ in EGPE solution, the bioavailability is 2.85-fold that after oral administration. The serum drug concentration was maintained at 4.0 mug/ml over 4 h, which is sufficient for the treatment of schistosomiasis. At the same time, no apparent side effects were found on the skin. EGPE may thus be a promising vehicle for the transdermal delivery of PZQ in the future.

Large-scale synthesis of a novel tri(8-hydroxyquioline) aluminum nanostructure.

A novel tri(8-hydroxyquioline) aluminum (AlQ3) nanostructure was prepared on large scale at low cost by low-temperature physical vapor deposition (PVD). The morphologies, the chemical bondings, and photoluminescence of the AlQ3 nanostructure were investigated by environmental scanning electronic microscopy (ESEM), Fourier transform infrared spectrum (FT-IR), and photoluminescence (PL) spectra, respectively. The AlQ3 nanostructure was composed of micro-sphere with nanowire-cluster growing on the surface. The diameter of micro-sphere and nanowire were about 5 microm and 80 nm, respectively. FT-IR results indicated that the AlQ3 molecule had a strong thermal stability under research conditions. The growth mechanism of the novel nanostructure was discussed. The novel organic nanostructure would be believed to attractive building field-emission devices and other optical devices.