This research focuses on the application of nanocellulose-stabilized silver nanoparticles (AgNPs) as a colorimetric sensing probe for mercury (II) detection. For this purpose, cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs) were employed with dual functions: a stabilizing agent and a dispersing matrix. The chemical and structural properties of the samples were analysed by various techniques such as XRD, FTIR, TEM and UV–Vis Spectroscopy. Due to different morphologies and surface functional groups in each type of nanocellulose, their effects on the AgNP formation as well as their response against mercury (II) ions were studied. It was discovered that the AgNPs stabilized by both types of nanocellulose can provide high sensitivity and selectivity towards mercury (II) ions. However, some interference caused by iron (III) ions was observed. This interference could be significantly reduced if the CNFs were employed during the AgNP preparation. Therefore, the advantage of using the CNFs as a stabilizing agent as well as a dispersing matrix will be discussed in detail. Furthermore, the possibility of fabrication into solid-state platforms (nanopapers) and response to mercury (II) ions will be demonstrated.
The cytotoxic activities against cancer cell lines of eight known sesquiterpene and phenylbutenoids, namely, (-)-beta-sesquiphellandrene (1), (E)-1-(3,4-dimethoxyphenyl)buta-1-ene (2), (E)-1-(3,4-dimethoxyphenyl)buta1,3-diene (3), (E)-1-(2,4,5-trimethoxyphenyl)buta-1-ene (4), (E)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene (5), (E)-4-(3,4-dimethoxyphenyl)buta-3-eneyl acetate (6), (+/-)-trans-3-(3,4-dimethoxyphenyl)-44 (E)-3,4-dimethoxystyryl] cyclohex-1-ene (7), and (+/-)-cis-3-(3,4-dimethoxyphenyl)-44 (E)-3,4-dimethoxystyryl]cyclohex-1-ene (8) were evaluated. All compounds were isolated from the rhizomes of Zingiber cassumunar Roxb. (Plai) using classical column chromatography. Compounds 1, 7, and 8 exhibited good cytotoxic activity against acute lymphoblastic leukemia (MOLT-3) with half maximal inhibitory concentration (IC50) values of 16.39 +/- 1.22, 16.41 +/- 3.68, and 14.38 +/- 0.78 mu g/ml; promyelocytic leukemia (HL-60) with IC50 values of 7.64 +/- 0.33, 15.25 +/- 0.88, and 13.02 +/- 0.91 mu g/ml; and hormone-independent breast cancer (MDA-MB-231) with IC50 values of 27.71 +/- 1.41, 28.99 +/- 2.30, and 27.94 +/- 2.24 mu g/ml, respectively. Compounds 3, 7, and 8 displayed good anticancer activity against cervical carcinoma (HeLa) with IC50 values of 18.68 +/- 0.62, 20.86 +/- 1.68, and 18.89 +/- 1.26 mu g/ml, respectively. The results showed that two diastereomers (7 and 8) have good activity against the broad range of tested cancer cell lines. From molecular docking analysis, the binding energy and interaction between the isolated compounds and topoisomerase II (Top2) was calculated and could be used to evaluate cytotoxic activity. Molecular docking showed that 7 and 8 interacted with Top2 (alpha and beta types) using two or three hydrogen bonding, whereas the other compounds that also displayed this interaction had at least one hydrogen bonding. Additionally, only 7 exhibited non-toxic effect against normal embryonic lung cell line (MRC-5); therefore, the biological activity of 7 can serve as a basis for the study of anti-cancer agents in the near future.
The essential oil from Zingiber cassumunar Roxb. (Plai) has long been used in Thai herbal remedies to treat inflammation, pains, sprains, and wounds. It was therefore loaded into an electrospun fibrous membrane for use as an analgesic and antibacterial dressing for wound care. The polymer blend between poly(lactic acid) and poly(ethylene oxide) was selected as the material of choice because its wettability can be easily tuned by changing the blend ratio. Increasing the hydrophilicity and water uptake ability of the material while retaining its structural integrity and porosity provides moisture balance and removes excess exudates, thereby promoting wound healing. The effect of the blend ratio on the fiber morphology and wettability was investigated using scanning electron microscopy (SEM) and contact angle measurement, respectively. The structural determination of the prepared membranes was conducted using Fourier-transform infrared spectroscopy (FTIR). The release behavior of (E)-1-(3,4-dimethoxyphenyl) butadiene (DMPBD), a marker molecule with potent anti-inflammatory activity from the fiber blend, showed a controlled release characteristic. The essential oil-loaded electrospun membrane also showed antibacterial activity against S. aureus and E. coli. It also exhibited no toxicity to both human fibroblast and keratinocyte cells, suggesting that the prepared material is suitable for wound dressing application.
A controlled release system of Plai (Zingiber cassumunar Roxb.) oil based on electrospun poly(lactic) acid (PLA) nanofiber mat was successfully developed. The physicochemical properties of the nanofibers loaded with select amounts of oil (15%, 20%, and 30% wt) were characterized using various techniques, including a morphological study using scanning electron microscopy (SEM), structural determination using Fourier transform infrared spectrometry (FTIR) and x-ray diffraction (XRD), as well as thermal properties study using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The loading content and the entrapment efficiency of Plai oil within the fiber mats were evaluated and were found to be remarkably high, ensuring that PLA was an appropriate material for Plai oil loading. The ability of the nanofiber mats to release (E)-1-(3,4-dimethoxyphenyl) butadiene (DMPBD) was also examined and the fiber mats showed controlled release characteristics. As the nanofiber mats have particularly high specific surface area with fully accessible and interconnected pore structures, a liquid medium with active ingredients will not be trapped in blind pores but can be fully released out of the fiber matrix. Furthermore, in vitro skin permeation of the active compound as well as a skin irritation were assessed using reconstructed human epidermis (EpiSkinTM). It was found that DMPBD could efficiently penetrate through the skin model. Moreover, the nanofiber mats containing Plai oil also showed no skin irritation, indicating them as promising prototypes for medical applications.
A novel class of fluorescent "turn on" probe based on the fluorescence resonance energy transfer (FRET) approach was designed, and successfully synthesized for the detection of hydrogen sulfide (H2S) both in vitro and in vivo. This new H2S responsive fluorescent probe was developed based on the basis of the dabsyl and fluorescein FRET system. In the presence of H2S, a fluorescence enhancement was markedly observed mainly due to the inhibition of the FRET process. This probe could quantitatively measure the level of H2S with the detection limit of 0.02 mu M. Cell imaging results demonstrated the potential applicability of a dabsylfluorescein probe for H2S detection in living cells.
Calothrixin B, a marine-derived compound, displays a broad spectrum of biological properties including anticancer effects. Calothrixin B has low water solubility, meaning that its therapeutic application is limited. In the present study, we explored the delivery of calothrixin B in the form of liposomal nanoparticles for its anticancer activity. Liposomes were prepared with cholesterol, and either DOPC or both DOPC and DOPE. Calothrixin B liposomes exhibited small sizes, ranging from 108 to 117 nm, and negative surface charges. High encapsulation efficiencies of calothrixin B (> 89%) were achieved in all formulations. Liposomes composed of DOPC, DOPE and cholesterol resulted in the release of 87% of calothrixin B within 48 h, while a slower release rate was observed for the liposome without DOPE, with 56% release of calothrixin B. The cytotoxicity of calothrixin B in DOPC, DOPE and cholesterol liposomes was more pronounced than that in liposomes without DOPE. In comparison with DMSO-calothrixin B, calothrixin B in DOPC, DOPE and cholesterol liposomes showed significantly increased toxicity against A549 and comparable activity against MCF-7. Confocal microscopy confirmed that DMSO-calothrixin B and calothrixin B liposomes could induce cell death by the same mechanism. Calothrixin B liposomes demonstrate significant potential as delivery carriers for cancer therapy.
A molecularly imprinted polymer (MIP) and a nanocomposite prepared from gold nanoparticles (AuNP) and poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate) (PEDOT:PSS) were deposited on a screen-printed carbon electrode (SPCE). The nanocomposite was prepared by one-pot simultaneous in-situ formation of AuNPs and PEDOT:PSS and was then inkjet-coated onto the SPCE. The MIP film was subsequently placed on the modified SPCE by co-electrodeposition of o-phenylenediamine and resorcinol in the presence of the antibiotic nitrofurantoin (NFT). Using differential pulse voltammetry (DPV), response at the potential of ~ 0.1 V (vs. Ag/AgCl) is linear in 1 nM to 1000 nM NFT concentration range, with a remarkably low detection limit (at S/N = 3) of 0.1 nM. This is two orders of magnitude lower than that of the control MIP sensor without the nanocomposite interlayer, thus showing the beneficial effect of AuNP-PEDOT:PSS. The electrode is highly reproducible (relative standard deviation 3.1% for n = 6) and selective over structurally related molecules. It can be re-used for at least ten times and was found to be stable for at least 45 days. It was successfully applied to the determination of NFT in (spiked) feed matrices and gave good recoveries.
A highly selective fluorescent chemosensor was designed, synthesized, and evaluated for Zn2+ recognition based on the photoinduced electron transfer (PET) mechanism. This azofluorescein was comprised of a fluorescein moiety acting as a fluorophore, a linker (NN) and a novel ionophore receptor generated by the coordination of the linker (NN) with phenoxyl and carboxyl functionalities to render a binding pocket for Zn2+ recognition. In the presence of Zn2+, a marked enhanced fluorescence change of 10-fold was observed. Under optimized conditions, a linear relationship between the fluorescence intensity and concentration of Zn2+ was observed with a detection limit of 1.2μM. This probe also exhibited selectivity for Zn2+ over other metals ions, especially Cd2+. The binding constant of the Zn2+–azofluorescein complex was determined to be 2.4×104M−1.
A key goal of our recent research efforts has been to develop novel 'triggerable nanoparticle' systems with real potential utility in vivo. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here we describe investigations into the use of enzymes to trigger RNAi-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG(2000)-peptidyl lipids with peptidyl moieties sensitive to tumour-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated siRNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nucleic acids to tumour cells in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability remains to be fully characterized.
Nanoparticle mediated functional delivery of plasmid DNA (pDNA) in vivo typically requires the formulation of pDNA-nanoparticles with a surface layer of stealth/biocompatibility polymer (usually poly(ethylene glycol) [PEG]). This PEG layer ensures the colloidal stability of pDNA-nanoparticles in biological fluids and minimizes nanoparticle interactions with the reticulo-endothelical system. Unfortunately, the presence of the PEG layer appears to contribute to a reduction in efficiency of functional delivery of pDNA once target cells are reached. For this reason, we have focused recent research efforts on "triggerable" nanoparticle systems. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here, we describe investigations into the potential use of enzymes to trigger pDNA-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG(2000)-peptidyl lipids with peptidyl moieties sensitive to tumor-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated pDNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nucleic acids to tumor cells in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability remains to be fully characterized.
A PEGylated peptide lipid sensitive to enzymatic cleavage has been designed for triggerable release of therapeutic nucleic acid in solid tumours. The peptide linker is a short peptide sequence, Ala-Ala-Pro-Val, which is highly sensitive to elastase, the proteolytic enzymes present in tumours. High and low charged nanoparticles were modified by addition of the synthetic PEG-AAPV-lipid. In vitro transfection study showed that PEG-AAPV-Iipid significantly improved transfection efficiency. In the absence of peptide the enzymatic cleavage does not occur and lower transfection efficiency was observed. Fluorescence microscopy confirmed the transfection result. It was demonstrated that PEG-AAPV-lipid can be triggered under enzyme environment, leading to dePEGylation and increase in transfection efficiency.