Partial molal volumes of ions in organic solvents from ultrasonic vibration potential and density measurements. III. Dimethylsulfoxide

The partial molal volumes of Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺, Cl^–, Br^–, I^–, and NO ₃ ^- in DMSO at 25°C have been determined from ultrasonic vibration potential data and density data for solutions of uni-univalent electrolytes. Hepler's semiemprirical equation has been used to split ionic partial molal volumes into geometric and electrostrictive contributions. The results obtained in this work confirm the conclusion of our previous studies, namely, that the contribution of electrostriction is essentially determined by the properties of that layer of atoms, 0.3 to 0.4 nm thick, in contact with the ion and by the degree of steric hindrance of the poles of the dipole of the solvent molecule. On the other hand, the geometric contribution depends on the size of the solvent molecule and also on the arrangement of the solvent molecules about the ions. It is shown that the geometric contribution to the partial molal volume of ions is largely increased when ions cannot come close enough to the poles of the solvent-molecule dipole, owing to steric hindrance.     

5-Aminolaevulinic acid-mediated photodynamic therapy in multidrug resistant leukemia cells

To verify if photodynamic therapy (PDT) could overcome multidrug resistance (MDR) when it it applied to eradicate minimal residual disease in patients with leukemia, we investigated the fluorescence kinetics of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) and the effect of subsequent photodynamic therapy on MDR leukemia cells, which express P-glycoprotein (P-gp), as well as on their parent cells. Evaluation of PpIX accumulation by flow cytometry showed that PpIX accumulated at higher levels in mdr-1 gene-transduced MDR cells (NB4/MDR) and at lower levels in doxorubicin-induced MDR cells (NOMO-1/ADR) than in their parent cells. A P-gp inhibitor could not increase PpIX accumulation. Measurement of extracellular PpIX concentration by fluorescence spectrometry showed that P-gp did not mediate the fluorescence kinetics of ALA-induced PpIX production. Assessment of ferrochelatase activity using high-performance liquid chromatography indicated that PpIX accumulation in drug-induced MDR cells was probably regulated by this enzyme. Assessment of phototoxicity of PDT using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that PDT was effective in NB4, NB4/MDR, NOMO-1 and NOMO-1/ADR cells, which accumulated high levels of PpIX, but not effective in K562 and K562/ADR cell lines, which accumulated relatively low levels of PpIX. These findings demonstrate that P-gp does not mediate the ALA-fluorescence kinetics, and multidrug resistant leukemia cells do not have cross-resistance to ALA-PDT.     

A Cyanine-based Liposomal Nanophotosensitizer for Enhanced Cancer Chemo-Photodynamic Therapy

Currently, chemotherapy is one of the most important treatment modalities for malignant tumors in the clinic, however, it exhibits some shortcomings, such as poor selectivity, limited efficacy and serious adverse effects. Therefore, synergistic therapy and accurate drug delivery at tumor sites become a promising strategy for achieving tumor eradication. Herein, a smart NIR fluorescence imaging-guided nanoliposome was fabricated by encapsulating a chemotherapeutic drug(doxorubicin, DOX), liposomes(L) and a near-infrared(NIR) photosensitizer(CY) to form L@CY@DOX, which could realize enhanced therapeutic efficacy of chemo-PDT in cancer therapy(PDT=photodynamic therapy). L@CY@DOX can induce mitochondrial apoptosis and produce severe toxicity at the cellular level, and L@CY@DOX can enrich in the tumor site, which significantly induces tumor death. In vitro and in vivo studies demonstrated that L@CY@DOX exhibited great antitumor efficacy compared with each one of these monotherapies, indicating that the combination of chemotherapy and PDT possessed potential development prospects and is anticipated in clinical application.     

超声搅拌磁流变抛光液的声场仿真分析

为了探究超声搅拌磁流变抛光液的制备及优化工艺,利用多物理场数值计算方法,建立了超声搅拌磁流变抛光液的声场仿真模型。研究了20 kHz下不同液位深度、超声变幅杆探入深度、不同功率下磁流变抛光液的声场分布。通过测量磁流变抛光液的声场强度对声场仿真进行了验证。结果表明:随着距变幅杆距离的增加,声强逐渐减弱,高声强区域主要分布在换能器轴线附近。声强在距变幅杆输出端20 mm范围内急剧衰减,变幅杆最佳探入深度为10 mm,增大功率有助于空化区域的扩大。声场仿真结果与实验测量结果基本一致,对磁流变抛光液的制备提供了数值计算基础。     

Anticancer Drugs: Recent Strategies to Improve Stability Profile,Pharmacokinetic and Pharmacodynamic Properties

In past decades, anticancer research has led to remarkable results despite many of the approved drugs still being characterized by high systemic toxicity mainly due to the lack of tumor selectivity and present pharmacokinetic drawbacks, including low water solubility, that negatively affect the drug circulation time and bioavailability. The stability studies, performed in mild conditions during their development or under stressing exposure to high temperature, hydrolytic medium or light source, have demonstrated the sensitivity of anticancer drugs to many parameters. For this reason, the formation of degradation products is assessed both in pharmaceutical formulations and in the environment as hospital waste. To date, numerous formulations have been developed for achieving tissue-specific drug targeting and reducing toxic side effects, as well as for improving drug stability. The development of prodrugs represents a promising strategy in targeted cancer therapy for improving the selectivity, efficacy and stability of active compounds. Recent studies show that the incorporation of anticancer drugs into vesicular systems, such as polymeric micelles or cyclodextrins, or the use of nanocarriers containing chemotherapeutics that conjugate to monoclonal antibodies can improve solubility, pharmacokinetics, cellular absorption and stability. In this study, we summarize the latest advances in knowledge regarding the development of effective highly stable anticancer drugs formulated as stable prodrugs or entrapped in nanosystems.     

Synthesis of a Rare Water-Soluble Silver(II)/Porphyrin and Its Multifunctional Therapeutic Effect on Methicillin-Resistant Staphylococcus aureus

Porphyrin derivatives are popular photodynamic therapy (PDT) agents; however, their typical insolubility in water has made it challenging to separate cells of organisms in a liquid water environment. Herein, a novel water-soluble 5,10,15,20-tetrakis(4-methoxyphenyl-3-sulfonatophenyl) porphyrin (TMPPS) was synthesized with 95% yield by modifying the traditional sulfonation route. The reaction of TMPPS with AgNO₃ afforded AgTMPPS an unusual Ag(II) oxidation state (97% yield). The free base and Ag(II) complex were characterized by matrix-assisted laser desorption ionization-mass spectroscopy, and ¹H nuclear magnetic resonance, Fourier-transform infrared, UV-vis, fluorescence, and X-ray photolectron spectroscopies. Upon 460 nm laser irradiation, AgTMPPS generated a large amount of ¹O₂, whereas no ⦁OH was detected. Antibacterial experiments on methicillin-resistant Staphylococcus aureus (MRSA) revealed that the combined action of Ag^Ⅱ ions and PDT could endow AgTMPPS with a 100% bactericidal ratio for highly concentrated MRSA (10⁸ CFU/mL) at a very low dosage (4 μM) under laser irradiation at 360 J/cm². Another PDT response was demonstrated by photocatalytically oxidizing 1,4-dihydronicotinamide adenine dinucleotide to NAD⁺ with AgTMPPS. The structural features of the TMPPS and AgTMPPS molecules were investigated by density functional theory quantum chemical calculations to demonstrate the efficient chemical and photodynamical effects of AgTMPPS for non-invasive antibacterial therapy.     

Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis

A systemic autoimmune condition known as rheumatoid arthritis (RA) has a significant impact on patients’ quality of life. Given the complexity of RA’s biology, no single treatment can totally block the disease’s progression. The combined use of co-delivery regimens integrating various diverse mechanisms has been widely acknowledged as a way to make up for the drawbacks of single therapy. These days, co-delivery systems have been frequently utilized for co-treatment, getting over drug limitations, imaging of inflammatory areas, and inducing reactions. Various small molecules, nucleic acid drugs, and enzyme-like agents intended for co-delivery are frequently capable of producing the ability to require positive outcomes. In addition, the excellent response effect of phototherapeutic agents has led to their frequent use for delivery together with chemotherapeutics. In this review, we discuss different types of nano-based co-delivery systems and their advantages, limitations, and future directions. In addition, we review the prospects and predicted challenges for the combining of phototherapeutic agents with conventional drugs, hoping to provide some theoretical support for future in-depth studies of nano-based co-delivery systems and phototherapeutic agents.     

Green Preparation of Durian Rind-Based Cellulose Nanofiber and Its Application in Aerogel

In this study, a green, highly efficient and low energy consumption preparation method of cellulose nanofiber (CNF) was developed by using agricultural and forestry waste durian rinds as raw materials. The power of ultrasonic treatment was successfully reduced to only 360 W with low molecular weight liquid DMSO. The obtained durian rind-based CNF had a diameter of 8–20 nm and a length of several micrometers. It had good dispersion and stability in water, and could spontaneously cross-link to form hydrogel at room temperature when the concentration was more than 0.5%. The microscopic morphology and compressive properties of CNF aerogels and composite cellulose aerogels prepared from durian rind-based CNF were evaluated. It was found that CNF could effectively prevent the volume shrinkage of aerogel, and the concentration of CNF had a significant effect on the microstructure and mechanical properties of aerogel. The CNF aerogel with 1% CNF exhibited a sheet structure braced by fibers, which had the strongest compression performance. The porosity of CNF aerogels was high to 99%. The compressive strength of the composite cellulose aerogel with durian rind-based CNF was effectively enhanced.     

Nano-Theranostics Constructed from Terpyridine-Modified Pillar [5]arene-Based Supramolecular Amphiphile and Its Application in Both Cell Imaging and Cancer Therapy

Theranostics play an important role in cancer treatment due to its realized real-time tracking of therapeutic efficacy in situ. In this work, we have designed and synthesized a terpyridine-modified pillar [5]arenes (TP5). By the coordination of terpyridine and Zn²⁺, the complex TP5/Zn was obtained. Then, supramolecular amphiphile can be constructed by using host–guest complexation between a polyethylene glycol contained guest (PM) and TP5/Zn. Combining the fluorescence properties from the terpyridine group and the amphiphilicity from the system, the obtained TP5/Zn/PM can further be self-assembled into fluorescent particles with diameters of about 150 nm in water. The obtained particles can effectively load anti-cancer drugs and realize living cell imaging and a precise release of the drugs.     

Removal of Amoxicillin from Aqueous Media by Fenton-like Sonolysis/H2O2 Process Using Zero-Valent Iron Nanoparticles

High concentrations of antibiotics have been identified in aqueous media, which has diminished the quality of water resources. These compounds are usually highly toxic and have low biodegradability, and there have been reports about their mutagenic or carcinogenic effects. The aim of this study was to apply zero-valent iron-oxide nanoparticles in the presence of hydrogen peroxide and the sonolysis process for the removal of the amoxicillin antibiotic from aqueous media. In this study, zero-valent iron nanoparticles were prepared by an iron chloride reduction method in the presence of sodium borohydride (NaBH₄), and the obtained nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and vibrating-sample magnetometry (VSM). Then, using a Fenton-like process, synthetic wastewater containing 100 to 500 mg/L amoxicillin antibiotic was investigated, and the effects of different parameters, such as the frequency (1 and 2 kHz), contact time (15 to 120 min), the concentration of hydrogen peroxide (0.3%, 0.5%, and 6%), the dose of zero-valent iron nanoparticles (0.05, 0.1, 0.5 g/L), and pH (3, 5, 10) were thoroughly studied. A pH of 3, hydrogen peroxide concentration of 3%, ultrasonic-wave frequency of 130 kHz, zero-valent iron nanoparticles of 0.5 g/L, and contaminant concentration of 100 mg/L were obtained as the optimal conditions of the combined US/H2O2/nZVI process. Under the optimal conditions of the combined process of zero-valent iron nanoparticles and hydrogen peroxide in the presence of ultrasonic waves, a 99.7% removal efficiency of amoxicillin was achieved in 120 min. The results show that the combined US/H2O2/nZVI process could be successfully used to remove environmental contaminants, including antibiotics such as amoxicillin, with a high removal percentage.