Molecular Characterization of Dissolved Organic Matter and Its Subfractions in Refinery Process Water by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

Dissolved organic matter (DOM) in oil refinery process water was fractionated by XAD-8 resin techniques into four subfractions: hydrophobic acid (HOA), hydrophobic base (HOB), hydrophobic neutral (HON), and hydrophilic substance (HIS) fractions. Negative and positive electrospray ion (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was used to characterize the composition of DOM and its subfractions. Compounds with multi-oxygen atoms were found to be predominant in DOM by either negative or positive ESI analysis, which are similar in composition to most other treated water samples. The DOM in the HOA fraction had a similar molecular composition to that of raw process water by negative ESI analysis. The DOM in the HOB fraction had a low molecular weight (MW) when analyzed by positive ESI, and basic nitrogen compounds, such as N₁ class species, were found to be predominant. The DOM in the HON fraction was predominantly O₂ class species. The DOM in the HIS fraction had a relatively wide MW distribution. All of the compounds of DOM in the HIS fraction exhibited low double bond equivalents (DBE) and low carbon numbers. The results showed that the use of the XAD-8 resin fractionation technique is valuable for characterizing trace quantities of DOM components in process water because their spectral peaks would otherwise be obscured by other abundant peaks. The origin and determination of chlorine-containing compounds, which are abundant in the negative ESI mass spectra of HOB, were discussed

Reduction-Cleavable Polymeric Vesicles with Efficient Glutathione-Mediated Drug Release Behavior for Reversing Drug Resistance

In the treatment of cancer, multidrug resistance (MDR) has been the major obstacle to the success of chemotherapy. The underlying mechanism relies on the overexpression of drug-efflux transporters that prevent the intracellular transport of the drug. In this study, reduction-cleavable vesicles were designed and developed with efficient glutathione-mediated drug-release behavior for reversing drug resistance. Polymeric vesicles were self-assembled from triblock copolymers with disulfide-bond-linked poly­(ethylene glycol) (PEG) and poly­(ε-benzyloxycarbonyl-l-lysine) (PzLL). Observations from transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) outline an obvious hollow structure surrounded by a thin outer layer, indicating the successful formation of the vesicles. Using fluorescently detectable doxorubicin hydrochloride (DOX·HCl) as the model drug, a significant acceleration of drug release regulated by glutathione (GSH) was found (>3-fold difference). Upon incubation of the DOX·HCl-loaded polymeric vesicles with the HeLa cervical cancer cell line exposed to glutathione, an enhanced nuclear accumulation of DOX·HCl was observed, elicited by the preferred disassembly of the vesicle structure under reducing conditions. Importantly, by using the gemcitabine hydrochloride (GC·HCl)-resistant breast cancer cell line MDA-MB-231, it was found that cell viability was significantly reduced after treatment with GC·HCl-loaded polymeric vesicles, indicating that these vesicles can help to reverse the drug resistance

Cleavable PEGylation and Hydrophobic Histidylation of Polylysine for siRNA Delivery and Tumor Gene Therapy

Polylysine with cleavable PEGylation and hydrophobic histidylation (mPEG-SS-Lys_<i>n</i>-r-His_<i>m</i>) was designed and developed for efficient siRNA delivery and tumor therapy. mPEG-SS-Lys_<i>n</i>-r-His_<i>m</i> was used to carry and deliver small interfering RNA (siRNA) for silencing endogenous vascular endothelial growth factor (VEGF) expression and inhibiting tumor growth in HepG2 tumor-bearing mice. In this gene vector, histidine­(Bzl) was selected for hydrophobic histidylation for the proton sponge ability of the imidazole ring and hydrophobic benzyl group. Cleavable PEGylation was introduced for in vivo circulation as well as selective PEG detachment in response to intracellular reduction condition in order to release the genetic payload. PEG detachment induced gene release was supported by agarose gel electrophoresis retardation assay, undertaken in the intracellular relevant reduction condition. In vitro transfection evaluation of histidylated copolymers, using pEGFP as genetic model, indicated significantly higher GFP expression than unmodified counterparts, comparable to the gold standard PEI. The efficacy of hydrophobic histidylation was found to be pronounced in mesenchymal stem cells (MSCs). In vivo application of the VEGF-siRNA package by tailored mPEG-SS-Lys_<i>n</i>-r-His_<i>m</i> showed distinct tumor suppression in terms of macroscopic tumor volume and molecular analysis

Molecular Characterization and Transformation of Dissolved Organic Matter in Refinery Wastewater from Water Treatment Processes: Characterization by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

A set of wastewaters sampled in a stream-by-stream flow of the process in a refinery wastewater treatment plant were characterized to investigate the molecular composition and transformation of dissolved organic matter (DOM). The samples were separated into organic and aqueous phase DOMs by solvent extraction and solid phase extraction (SPE). Volatile and semivolatile compounds in the organic phase were characterized by gas chromatography–mass spectrometry (GC-MS); DOMs in the organic and aqueous phases were characterized by negative ion electrospray (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The aqueous phase DOMs exhibited a more complex molecular composition than other complex mixtures investigated by far, in which there were totally 76 compound class species identified in a single mass spectrum. Refinery wastewater DOMs have lower values of double bond equivalent (DBE) and O/C ratio than those of natural organic matter (NOM) in fresh and marine waters. The organic phase DOM occupied the major TOC value, but was liable to be degraded in the biological process. Some humic-like substances presented in the aqueous DOM were found resistant to the treatment processes by the ESI FT-ICR MS based semiquantitative results

“Minimalist” Nanovaccine Constituted from Near Whole Antigen for Cancer Immunotherapy

One of the major challenges in vaccine design has been the over dependence on incorporation of abundant adjuvants, which in fact is in violation of the “minimalist” principle. In the present study, a compact nanovaccine derived from a near whole antigen (up to 97 wt %) was developed. The nanovaccine structure was stabilized by free cysteines within each antigen (ovalbumin, OVA), which were tempospatially exposed and heat-driven to form an extensive intermolecular disulfide network. This process enables the engineering of a nanovaccine upon integration of the danger signal (CpG-SH) into the network during the synthetic process. The 50 nm-sized nanovaccine was developed comprising approximately 500 antigen molecules per nanoparticle. The nanovaccine prophylactically protected 70% of mice from tumorigenesis (0% for the control group) in murine B16-OVA melanoma. Significant tumor inhibition was achieved by strongly nanovaccine-induced cytotoxic T lymphocytes. This strategy can be adapted for the future design of vaccine for a minimalist composition in clinical settings

Additional file 1 of Triptolide with hepatotoxicity and nephrotoxicity used in local delivery treatment of myocardial infarction by thermosensitive hydrogel

Supplementary Material

Additional file 1 of Pathologically catalyzed physical coating restores the intestinal barrier for inflammatory bowel disease therapy

Supplementary Material