Synthesis of zwitterionic N-chlorohydantoins for antibacterial applications.

Two novel zwitterionic N-chlorohydantoin biocides, containing an N-chlorohydantoin unit and a sulfobetaine unit or a carboxybetaine unit, were chemically synthesized and characterized. Using the quaternary ammonium N-chlorohydantoin as control, the antibacterial activity of synthetic zwitterionic N-chlorohydantoins was challenged and the antibacterial data showed that carboxybetaine N-chlorohydantoin exhibited distinctively higher biocidal efficacy than QA counterpart, while sulfobetaine N-chlorohydantoin displayed slightly inferior antimicrobial efficacy. Our results may inspire further exploration of more zwitterionic N-chlorohydantoin analogs for antibacterial application.

Influence of CNTs on the Crystalline Microstructure and Ferroelectric Behavior of P(VDF-TrFE).

We investigate the effect of carbon nanotubes (CNTs) on the crystalline microstructure and ferroelectric behavior of polyvinylidene fluoride- co-trifluoroethylene (P(VDF-TrFE)). X-ray analysis suggests that CNT can act as a template and direct the chain orientation of P(VDF-TrFE) crystals. In the presence of CNTs, the molecular chain axis ( c axis) of the ß-phase crystal is oriented parallel to the long axis of CNTs. Moreover, we find that this templating effect did not cause a polymorph transition. For P(VDF-TrFE)/CNT composites, the crystallinity of P(VDF-TrFE) is slightly decreased. The orientation of the c axis induced by the templating effect of CNTs has a significant impact on the ferroelectric behavior of P(VDF-TrFE). As compared to a pure P(VDF-TrFE) film, the remnant polarization of the P(VDF-TrFE)/CNT composite is enhanced. Correspondingly, the piezoelectric property of the P(VDF-TrFE)/CNT composite shows a significant enhancement.

Synergistic effects of eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes on lung cancer in vitro and in vivo.

PURPOSE: LKB1 and FUS1 are two kinds of new tumor suppressor genes as well as early-stage genes in lung cancer. Recent studies showed that LKB1 and FUS1 play important roles in lung carcinogenesis process. We hypothesized that combined gene therapy with LKB1 and FUS1 could inhibit lung cancer growth and development synergistically. METHODS: In this study, two kinds of tumor suppressor genes, LKB1 and FUS1, were constructed in an eukaryotic coexpression plasmid pVITRO(2), and then, we evaluated the synergistic effects of the two genes on anticancer activity and explored the relevant molecular mechanisms. RESULTS: We defined coexpression of LKB1 and FUS1 could synergistically inhibited lung cancer cells growth,invasion and migration and induced the cell apoptosis and arrested cell cycle in vitro. Intratumoral administration of liposomes: pVITRO(2)­LKB1­FUS1 complex (LPs­pVITRO(2)­LKB1­FUS1) into subcutaneous lung tumor xenograft resulted in more significant inhibition of tumor growth. Furthermore, intravenous injection of LPs­pVITRO(2)­LKB1­FUS1 into mice bearing experimental A549 lung metastasis demonstrated synergistic decrease in the number of metastatic tumor nodules. Finally, combined treatment with LKB1 and FUS1 prolonged overall survival in lung tumor-bearing mice. Further study showed tha tthe synergistic anti-lung cancer effects of coexpression ofLKB1 and FUS1 might be related to upregulation of p-p53, p-AMPK and downregulation of p-mTOR, p-FAK, MMPs, NEDD9, VEGF/R and PDGF/R. CONCLUSIONS: Our results suggest that combined therapy with eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes may be a novel and efficient treatment strategy for human lung cancer.

Polyurethane (PU)-derived photoactive and copper-free clickable surface based on perfluorophenyl azide (PFPA) chemistry.

The anchoring and capturing roles of perfluorophenyl azide (PFPA) were combined to produce a universal polyurethane (PU)-derived photoactive surface platform (PU-1-PFPA). The resultant platform was confirmed by contact angle, attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) analyses. Upon UV light activation, native heparin was coupled directly onto PU-1-PFPA to yield a substrate with antithrombogenic properties. The same level of antithrombogenic activity was achieved when the recovered heparin was photo-coupled onto PU-1-PFPA. In addition, at room temperature and in the absence of copper catalysts, PU-1-PFPA achieved oriented immobilization of functional moieties bearing an alkynyl functional group.

New biocide with both N-chloramine and quaternary ammonium moieties exerts enhanced bactericidal activity.

Considering the rise of antibiotic resistance, the development of new antibacterial agents with improved biocidal functions is urgently required. In this study, ionic 5,5-dimethylhydantoin (DMH) analogues containing either a quaternary ammonium moiety (2)-4) or a phosphonate functional group (5),-6), were designed and synthesized to investigate the possible enhancing effect of quaternary ammonium moieties on the antibacterial performance of N-chloramines. These ionic DMH analogues were converted to their N-chloramine counterparts either in free form or after being covalently immobilized on a polymer surface via the "click" chemistry method. In the subsequent antimicrobial assessment against multi-drug-resistant Escherichia coli (MDR-E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), chlorinated 2 and 3, the cyclic N-chloramines with a structural cation, exhibited distinctly enhanced biocidal functions in solution and after immobilization on surfaces.

Diol glycidyl ether-bridged cyclens: preparation and their applications in gene delivery.

Polymeric 1,4,7,10-tetraazacyclododecanes (cyclens) using diol glycidyl ether with different chain length as bridges (5a-e) were designed and synthesized from various diols, 1,7-diprotected cyclen and epichlorohydrin. The molecular weights of the title polymers were measured by GPC with good polydispersity. Agarose gel retardation and fluorescent titration using ethidium bromide showed good DNA-binding ability of 5. They could retard plasmid DNA (pDNA) at an N/P ratio of 4-6 and form polyplexes with sizes around 100-250 nm from an N/P ratio of 10 to 60 and relatively low zeta-potential values (5-22 mV). The cytotoxicity of 5 assayed by MTT is much lower than that of 20 kDa PEI. In vitro transfection against A549 and 293 cells showed that the transfection efficiency (TE) of 5c/DNA polyplexes is close to that of 20 kDa PEI at an N/P ratio of 5. Structure-activity relationship (SAR) of 5 was discussed in their DNA-binding, cytotoxicity, and transfection studies. The TE of 5c/DNA polyplexes could be improved by the introduction of 50 µM of chloroquine, the endosomolytic agents, to pretreated cells. These studies may extend the application areas of macrocyclic polyamines, especially for cyclen.

Effect of Fraxiparine, a type of low molecular weight heparin, on the invasion and metastasis of lung adenocarcinoma A549 cells.

Lung cancer is one of the most highly malignant tumors, and a significant threat to human health. Lung cancer patients often exhibit tumor cell invasion and metastasis, which often render current treatments ineffective. Recently, the beneficial effects of low molecular weight heparin (LMWH) on cancer metastasis were reported in pre-clinical research studies. LMWH may be a potential drug for cancer therapy. However, the mechanism of LMWH on the invasion and metastasis of cancer has yet to be determined. This study investigated the effects of Fraxiparine on the proliferation, invasion and metastasis of the human lung adenocarcinoma A549 cell line. MTT assay and flow cytometry showed that Fraxiparine slightly inhibited the cell viability dose- and time-dependently, but did not arrest the A549 cells in the G1 phase nor induce early apoptosis. The transwell chamber assay showed that Fraxiparine significantly suppressed the invasion and migration of the A549 cells in vitro. Fraxiparine also markedly inhibited the adhesion of the A549 cells to Matrigel. The RT-PCR assay demonstrated that the reduction in invasion and metastasis may be related to the up-regulation of nm23-H1 and the down-regulation of the heparanase expression. Moreover, the RT-PCR assay and Western blot analysis demonstrated that down-regulation of the expression of integrin ß1 and ß3, as well as that of matrix metalloproteinase-2 and -9 may be responsible for the inhibition of the invasion and metastasis of A549 cells by Fraxiparine.

Synthesis and application of photoaffinity probe containing an intact isoprenoid chain.

Two novel chemical probes each carrying an intact isoprenoid chain, a biotin tag and a benzophenone moiety were synthesized. Photoaffinity labeling of the Saccharomyces cerevisiae cell lysate revealed that these probes could selectively trap some proteins, and proteins with molecular weight of approximately 70 KDa appeared as a major band upon Streptavidin blot analysis.

Chemical proteomic study of isoprenoid chain interactome with a synthetic photoaffinity probe.

A chemical proteomic approach was developed for profiling the noncovalent interactome of isoprenoid chain in the yeast proteome. A chemical probe that harbors a biotin moiety and a photoreactive benzophenone group linked to the terminal of geranyl group was synthesized. Photoaffinity labeling was performed by incubating the Saccharomyces cerevisiae proteome and the probe under 365 nm UV light. Thirty proteins were identified by immobilized NeutraAvidin enrichment, on-bead digestion, online 2-D nano-LC/MS/MS identification and semi-quantitative proteomic analysis. As noted by Gene Ontology annotation, the identified proteins demonstrate a wide range of catalytic activity in several biological processes, especially in metabolism and biosynthesis. Further data analysis shows that hydrophobic binding of the synthetic probe is potentially the major interaction force leading to covalent labeling. These results argue that intracellular allosteric interactions conferred by the isoprenoid chain of the corresponding chemical structures may be widespread at an interactomic level.