Functionalized Ultrasmall Iron Oxide Nanoparticles for T1-Weighted Magnetic Resonance Imaging of Tumor Hypoxia

Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment’s therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitive T₁-weighted MRI probe (Fe₃O₄-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe₃O₄) nanoparticles. The results of in vitro and in vivo experiments show that Fe₃O₄-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia via T₁-weighted MRI. These promising results may unlock the potential of Fe₃O₄ nanoparticles as T₁-weighted contrast agents for the development of clinical hypoxia probes.     

Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma

Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75–110 nm with size dispersion (PDI) within the range of 0.19–0.50 and zeta-potential approximately –10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability—their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.     

Stab-Resistant Performance of the Well-Engineered Soft Body Armor Materials Using Shear Thickening Fluid

Stab-resistant body armor can effectively prevent sharp instruments from attacking the protected parts and reduce the threat to human bodies. Shear thickening fluid (STF) is a kind of smart material with variable viscosity and its viscosity can change significantly with external stimuli. The soft and adaptive characteristics of STF provide a new idea for improving the performance of stab-proof materials. In this work, three kinds of soft anti-stabbing materials were designed and prepared with aramid, poly–p–phenylene benzodioxazole (PBO), and carbon fiber fabrics impregnated with STF. Quasi-static puncture tests and dynamic impact tests were conducted to compare the performance of different anti-stabbing structures. The results showed that the peak piercing force of the STF-treated fabrics in the puncture testing was greatly increased than that of neat samples. Against the D2 knife, the maximum impact load of STF/PBO fiber fabric was increased from 55.8 N to 72.9 N, increasing by 30.6%. Against the D3 spike, the maximum impact load of STF/aramid fabric was increased from 128.9 N to 254.7 N, increasing by 197.6%. The mechanical properties of fibers were important factors for the resistance to knives, and the fabric structure was the key point to bear the spike. Optical photographs of fabric fractures and scanning electron microscope analysis indicated that the STF effectively limited the slip of the fiber bundle when the tool penetrated the fabric, which played a positive role in maintaining the tightness and integrity of the fabric structure.     

A New Ratiometric Fluorescent Probe Based on BODIPY for Highly Selective Detection of Hydrogen Sulfide

Hydrogen sulfide (H₂S) as small molecular signal messenger plays key functions in numerous biological processes. The imaging detection of intracellular hydrogen sulfide is of great significance. In this work, a ratiometric fluorescent probe BH based on an asymmetric BODIPY dye for detection of H₂S was designed and synthesized. After the interaction with hydrogen sulfide, probe display colorimetric and ratiometric fluorescence response, with its maximum emission fluorescence wavelength red-shifted from 542 nm to 594 nm, which is attributed to the sequential nucleophilic reaction of H₂S leading to enhanced molecular conjugation after ring formation of the BODIPY skeleton. A special response mechanism has been fully investigated by NMR titration and MS, so that the probe has excellent detection selectivity. Furthermore, probe BH has low cytotoxicity and fluorescence imaging experiments indicate that it can be used to monitor hydrogen sulfide in living cells.     

New Insight into CO2 Reduction to Formate by In Situ Hydrogen Produced from Hydrothermal Reactions with Iron

To reveal the nature of CO₂ reduction to formate with high efficiency by in situ hydrogen produced from hydrothermal reactions with iron, DFT calculations were used. A reaction pathway was proposed in which the formate was produced through the key intermediate species, namely iron hydride, produced in situ in the process of hydrogen gas production. In the in situ hydrogenation of CO₂, the charge of H in the iron hydride was −0.135, and the Fe–H bond distance was approximately 1.537 Å. A C-H bond was formed as a transition state during the attack of H^δ− on C^δ+. Finally, a HCOO species was formed. The distance of the C-H bond was 1.107 Å. The calculated free energy barrier was 16.43 kcal/mol. This study may provide new insight into CO₂ reduction to formate in hydrothermal reactions with metal.     

A Sensitive and Selective Colorimetric Method Based on the Acetylcholinesterase-like Activity of Zeolitic Imidazolate Framework-8 and Its Applications

In this study, a simple colorimetric method was established to detect copper ion (Cu²⁺), sulfathiazole (ST), and glucose based on the acetylcholinesterase (AChE)-like activity of zeolitic imidazolate framework-8 (ZIF-8). The AChE-like activity of ZIF-8 can hydrolyze acetylthiocholine chloride (ATCh) to thiocholine (TCh), which will further react with 5,5′-dithiobis (2-nitrobenzoic acid) (DTNB) to generate 2-nitro-5-thiobenzoic acid (TNB) that has a maximum absorption peak at 405 nm. The effects of different reaction conditions (buffer pH, the volume of ZIF-8, reaction temperature and time, and ATCh concentration) were investigated. Under the optimized conditions, the value of the Michaelis-Menten constant (K_m) is measured to be 0.83 mM, which shows a high affinity toward the substrate (ATCh). Meanwhile, the ZIF-8 has good storage stability, which can maintain more than 80.0% of its initial activity after 30 days of storage at room temperature, and the relative standard deviation (RSD) of batch-to-batch (n = 3) is 5.1%. The linear dependences are obtained based on the AChE-like activity of ZIF-8 for the detection of Cu²⁺, ST, and glucose in the ranges of 0.021–1.34 and 5.38–689.66 µM, 43.10–517.24 µM, and 0.0054–1.40 mM, respectively. The limit of detections (LODs) are calculated to be 20.00 nM, 9.25 µM, and 5.24 µM, respectively. Moreover, the sample spiked recoveries of Cu²⁺ in lake water, ST in milk, and glucose in strawberry samples were measured, and the results are in the range of 98.4–115.4% with the RSD (n = 3) lower than 3.3%. In addition, the method shows high selectivity in the real sample analysis.     

Simultaneous Extraction and Determination of Characteristic Steroidal Saponins and Homoisoflavonoids in Zhejiang Ophiopogon japonicus

Zhejiang Ophiopogon japonicus (ZOJ) is a specific variety of Ophiopogon japonicus with characteristic steroidal saponins and homoisoflavonoids, which are also main pharmacodynamic constituents with clinical effects, including curing inflammation and cardiovascular diseases. However, few analysis methods were applied to simultaneously and quantitatively determine two kinds of its constituents, and hazardous organic solvents are mostly used for extraction. In this study, a new validated simultaneous extraction and determination method for four characteristic steroidal saponins and homoisoflavonoids in ZOJ was established by ionic liquid–ultrasonic extraction (IL-UAE) combined with HPLC-DAD-ELSD analysis, which can be used for the quality control of ZOJ. Chromatographic separation was performed with a DAD wavelength at 296 nm, and the ELSD parameters of the drift tube temperature (DTT), atomizer temperature (AT), and nitrogen gas pressure (NGP) were set at 20% heating power, 70 °C, and 25 psi, respectively. The optimal IL-UAE conditions were 1 mol/L [Bmim]CF₃SO₃ aqueous solution, a liquid–material ratio of 40 mL/g, and an ultrasonic time of 60 min. The proposed method is reliable, reproducible, and accurate, which were verified with real sample assays. Consequently, this work will be helpful for the quality control of ZOJ. It can also present a promising reference for the simultaneous extraction and determination of different kinds of constituents in other medicinal plants.     

The Taste-Masking Mechanism of Chitosan at the Molecular Level on Bitter Drugs of Alkaloids and Flavonoid Glycosides from Traditional Chinese Medicine

Taste masking of traditional Chinese medicines (TCMs) containing multiple bitter components remains an important challenge. In this study, berberine (BER) in alkaloids and phillyrin (PHI) in flavonoid glycosides, which are common bitter components in traditional Chinese medicines, were selected as model drugs. Chitosan (CS) was used to mask their unfriendly taste. Firstly, from the molecular level, we explained the taste-masking mechanism of CS on those two bitter components in detail. Based on those taste-masking mechanisms, the bitter taste of a mixture of BER and PHI was easily masked by CS in this work. The physicochemical characterization results showed the taste-masking compounds formed by CS with BER (named as BER/CS) and PHI (named as PHI/CS) were uneven in appearance. The drug binding efficiency of BER/CS and PHI/CS was 50.15 ± 2.63% and 67.10 ± 2.52%, respectively. The results of DSC, XRD, FTIR and molecular simulation further indicated that CS mainly masks the bitter taste by disturbing the binding site of bitter drugs and bitter receptors in the oral cavity via forming hydrogen bonds between its hydroxyl or amine groups and the nucleophilic groups of BER and PHI. The taste-masking evaluation results by the electronic tongue test confirmed the excellent taste-masking effects on alkaloids, flavonoid glycosides or a mixture of the two kinds of bitter components. The in vitro release as well as in vivo pharmacokinetic results suggested that the taste-masked compounds in this work could achieve rapid drug release in the gastric acid environment and did not influence the in vivo pharmacokinetic results of the drug. The taste-masking method in this work may have potential for the taste masking of traditional Chinese medicine compounds containing multiple bitter components.     

Iron Porphyrin as a Cytochrome P450 Model for the Degradation of Dye

Organic dyes are widely used in the textile, biological, medical and other fields. However, a serious environmental problem has appeared because of the presence of organic dyes in industrial aqueous effluents. Thus, the efficient treatment of organic dyes in industrial wastewaters is currently in real demand. The current study investigated the oxidative degradation of the organic dye gentian violet by meso-tetra(carboxyphenyl) porphyriniron(III), [Fe^III(TCPP)] as a cytochrome P450 model and iodosylbenzene (PhIO) as an oxidant at room temperature. The degradation reaction was monitored by UV–vis absorption spectroscopy via the observation of UV–vis spectral changes of the gentian violet. The results showed that the efficiency of catalyzed degradation reached more than 90% in 1 h, indicating the remarkable oxidative degradation capacity of the [Fe^III(TCPP)]/PhIO system, which provided an efficient approach for the treatment of dyeing wastewater.