Diatomite biosilica nanocarriers for siRNA transport inside cancer cells

BackgroundDiatomite is a natural porous biomaterial of sedimentary origin, formed by fragments of diatom siliceous skeletons, called “frustules”. Due to large availability in many areas of the world, chemical stability, and non-toxicity, these fossil structures have been widespread used in lot of industrial applications, such as food production, water extracting agent, production of cosmetics and pharmaceutics. However, diatomite is surprisingly still rarely used in biomedical applications. In this work, we exploit diatomite nanoparticles for small interfering ribonucleic acid (siRNA) transport inside human epidermoid cancer cells (H1355).MethodsMorphology and composition of diatomite microfrustules (average size lower than 40 μm) are investigated by scanning electron microscopy equipped by energy dispersive X-ray spectroscopy, Fourier transform infrared analysis, and photoluminescence measurements. Nanometric porous particles (average size lower than 450 nm) are obtained by mechanical crushing, sonication, and filtering of micrometric frustules. siRNA bioconjugation is performed on both micrometric and nanometric fragments by silanization.ResultsIn-vitro experiments show very low toxicity on exposure of the cells to diatomite nanoparticle concentration up to 300 μg/ml for 72 h. Confocal microscopy imaging performed on cancer cells incubated with siRNA conjugated nanoparticles demonstrates a cytoplasmatic localization of vectors. Gene silencing by delivered siRNA is also demonstrated.ConclusionOur studies endorse diatomite nanoparticles as non-toxic nanocarriers for siRNA transport in cancer cells.General significancesiRNA is a powerful molecular tool for cancer treatment but its delivery is inefficient due to the difficulty to penetrate the cell membrane. siRNA-diatomite nanoconjugate may be well suited for delivery of therapeutic to cancer cells.     

Peptide-based hydrogel nanoparticles as effective drug delivery agents

Peptide-based hydrogel nanoparticles represent a promising alternative to current drug delivery approaches. We have previously demonstrated that the Fmoc-FF aromatic dipeptide building block can self-assemble in aqueous solutions to form nano-scaled ordered hydrogels of remarkable mechanical rigidity. Here, we present a scalable process for the assembly of this peptide into hydrogel nanoparticles (HNPs) aimed to be utilized as potential drug delivery carriers. Fmoc-FF based HNPs were formulated via modified inverse-emulsion method using vitamin E-TPGS as an emulsion stabilizer and high speed homogenization. The formed HNPs exhibited two distinguishable populations with an average size of 21.5 ± 1.3 and 225.9 ± 0.8 nm. Gold nanoparticles were encapsulated within the hydrogel nanoparticles as contrast agents to monitor the formation of the assemblies and their ultrastructural properties. Next, we demonstrated a robust experimental procedure developed and optimized for the formulation, purification, storage and handling procedures of HNPs. Encapsulation of doxorubicin (Dox) and 5-flourouracil (5-Fu) within the HNPs matrix showed release kinetics of the drugs depending on their chemical structure, molecular weight and hydrophobicity. The results clearly indicate that Fmoc-FF based hydrogel nanoparticles have the potential to be used as encapsulation and delivery system of various drugs and bioactive molecules.     

Surface modification of iron oxide nanoparticles with polyarginine as a highly positively charged magnetic nano-adsorbent for fast and effective recovery of acid proteins

Polyarginine has been successfully bound onto iron oxide nanoparticles via carbodiimide activation as a highly positively charged magnetic nano-adsorbent for protein separation. They were nearly superparamagnetic with a mean diameter of 10.3 ± 2.36 nm, and the binding process did not change the spinel structure of iron oxide. From the analyses of FTIR spectra and zeta potential, the binding of polyarginine on the surface of iron oxide was confirmed and the resultant polyarginine-coated magnetic nanoparticles (PA-MNPs) were positively charged even up to pH 11. By thermogravimetric analysis, the typical product contained about 7.1 wt% of polyarginine. From the adsorption of the proteins with different pI values, the resultant PA-MNPs were found to be quite efficient for the fast and effective adsorption of acid proteins. For the typical acid protein, bovine serum albumin (BSA), the adsorption equilibrium was achieved within few minutes and obeyed the Langmuir isotherm equation. At pH 7 and 25 °C, the maximum adsorption capacity and equilibrium constant were 67.6 mg/g and 0.0623 L/mg, respectively. Moreover, by SDS–polyacrylamide gel electrophoresis, the capability of PA-MNPs for the separation of BSA-lysozyme mixture and egg white was further confirmed. Accordingly, the PA-MNPs were useful for the fast and effective magnetic recovery of acid proteins.     

Characterization and in vitro cytotoxicity of doxorubicin-loaded γ-polyglutamic acid-chitosan composite nanoparticles

In this study, γ-polyglutamic acid (γ-PGA) and chitosan (CS) nanoparticles were characterized as a carrier for the anti-cancer drug doxorubicin (DOX). Using ionic complexation between the positively charged DOX and the negatively charged polyelectrolyte γ-PGA, DOX:γ-PGA complexes were produced with an efficiency of approximately 99%. SEM micrographs demonstrated that the complexation of γ-PGA and DOX alone does not lead to the formation of nanoparticles and that the addition of a third component, chitosan, is required. Drug-loaded DOX:γ-PGA:CS nanoparticles were produced with particle sizes ranging from ~150 to ~630 nm. The stability of the DOX:γ-PGA:CS nanoparticles was examined by suspending the nanoparticles in different kinds of aqueous media. For the first time, in vitro studies with DOX-loaded nanoparticles demonstrated the cytotoxicity of the nanoparticles against a human oral squamous cell carcinoma cell line (HN-5a). Non-drug-loaded γ-PGA:CS nanoparticles did not display cytotoxic effects. It was shown that the encapsulated or surface-bound DOX did not lose its bioactivity and the prepared drug-loaded particles exhibited a considerable anti-proliferative activity against the human cancer cell line.     

Facile synthesis,physiochemical characterization and bio evaluation of sulfadimidine capped cobalt nanoparticles

Due to their less expensive, environment friendly nature, and their natural abundance of cobalt have attained more significant attention for the synthesis of cobalt nanoparticles. In the present study, we report the facile synthesis of cobalt nanoparticles using a straight forward chemical reduction approach of cobalt chloride with sodium borohydride and capping of sulfadimidine. sulfadimidine has strong capping eligibility on the surface of nanoparticles due to its chemical stability and is an applicable as stabilizer due to the existence of an amine bond. The as-synthesized sulfadimidine stabilized cobalt nanoparticles (Co-SD NPs) were characterized by using various spectroscopic and microscopic analysis like UV–Visible spectroscopy (UV–Vis), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), High-Resolution Transmission electron microscopy (HR-TEM), and Fourier-transform infrared spectroscopy (FT-IR). The XRD analysis exhibited the triclinic crystal structure of the as-synthesized cobalt nanoparticles and FT-IR analysis confirmed the capping of sulfadimidine via monodentate interaction. The HR-TEM analysis displayed the size of the cobalt nanoparticles approximately 3–5 nm. The antibacterial properties of the sulfadimidine stabilized cobalt nanoparticles (Co-SD NPs) were tested against various bacterial strains such as Klebsiella pneumonia (KP), Escherichia coli (EC) and Pseudomonas syringae (PS) by using agar disc diffusion approach. The results of sulfadimidine capped cobalt nanoparticles displayed the enhanced biological properties against the tested gram-negative bacteria.     

A therapeutic trial of human melanomas with combined small interfering RNAs targeting adaptor molecules p130Cas and paxillin activated under expression of ganglioside GD3

We previously demonstrated that focal adhesion kinase (FAK), p130Cas and paxillin are crucially involved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells. Therefore, molecules existing in the GD3-mediated signaling pathway could be considered as suitable targets for therapeutic intervention in malignant melanoma. The aim of this study was to determine whether blockade of p130Cas and/or paxillin by RNAi suppresses melanoma growth. We found a suitable dose (40 μM siRNA, 25 μl/tumor) of the siRNA to suppress p130Cas in the xenografts generated in nu/nu mice. Based on these results, we performed intratumoral (i.t.) treatment with anti-p130Cas and/or anti-paxillin siRNAs mixed with atelocollagen as a drug delivery system in a xenograft tumor of a human melanoma cell line, SK-MEL-28. Mixture of atelocollagen (1.75%) and an siRNA (500 or 1000 pmol/tumor) was injected into the tumors every 3 days after the first injection. An siRNA against human p130Cas markedly suppressed tumor growth of the xenograft in a dose-dependent manner, whereas siRNA against human paxillin slightly inhibited the tumor growth. A control siRNA against firefly luciferase showed no effect. To our surprise, siRNA against human p130Cas (500 or 1000 pmol/tumor) combined with siRNA against human paxillin dramatically suppressed tumor growth. In agreement with the tumor suppression effects of the anti-p130Cas siRNA, reduction in Ki-67 positive cell number as well as in p130Cas expression was demonstrated by immunohistostaining. These results suggested that blockade of GD3-mediated growth signaling pathways by siRNAs might be a novel and promising therapeutic strategy against malignant melanomas, provided signaling molecules such as p130Cas and paxillin are significantly expressed in individual cases. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.     

Fungus mediated synthesis of gold nanoparticles and their conjugation with genomic DNA isolated from Escherichia coli and Staphylococcus aureus

Biological systems employing microorganisms have been used as an alternative to conventional chemical techniques for synthesizing gold nanoparticles. In the present study, gold nanoparticles have been synthesized from the supernatant broth (SB) and live cell filtrate (LCF) of the industrially important fungus Penicillium rugulosum. Additionally, potato dextrose broth (PDB) medium which is used for the growth of the fungus has also been able to synthesize gold nanoparticles. The size of the particles has been investigated by Bio-TEM before purification as well as after purification to find the difference in morphology pattern of the nanoparticles. Different characterization techniques like X-ray diffraction (XRD), infra-red (FTIR), X-ray photoelectron (XPS) and UV–vis spectroscopy have been used for analysis of the particles. SB of the fungus has yielded nanoparticles with better morphology and hence further optimization studies were conducted for controlling the size and shape of the above by altering pH and concentration of gold salt. A pH range of 4–6 has favored the synthesis process whereas increasing concentration of gold salt (beyond 2 mM) has resulted in the formation of bigger sized and aggregated nanoparticles. The optimized nanoparticles have been used to conjugate with isolated genomic DNA of bacteria Escherichia coli and Staphylococcus aureus. Visual observation of agarose gel electrophoresis images confirmed the binding of gold nanoparticles (4 μL and 6 μL) with isolated DNA (2 μL) fragments of both the organisms. The slight red shift of the surface plasmon (SP) band and minor aggregations noticed in Bio-TEM images for the DNA conjugated gold nanoparticles indicates that the genomic DNA could stabilize the particles against aggregation owing to negatively charged phosphate backbone.     

Synergism of three-drug combinations of sanguinarine and other plant secondary metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells

We determined the ability of some phytochemicals, including alkaloids (glaucine, harmine, and sanguinarine), phenolics (EGCG and thymol), and terpenoids (menthol, aromadendrene, β-sitosterol-O-glucoside, and β-carotene), alone or in combination with the saponin digitonin to reverse the relative multi-drug resistance of Caco-2 and CEM/ADR5000 cells to the chemotherapeutical agent doxorubicin. The IC₅₀ of doxorubicin in Caco-2 and CEM/ADR5000 was 4.22 and 44.08 μM, respectively. Combination of non-toxic concentrations of individual secondary metabolite with doxorubicin synergistically sensitized Caco-2 and CEM/ADR5000 cells, and significantly enhanced the cytotoxicity of doxorubicin. Furthermore, three-drug combinations (secondary metabolite + digitonin + doxorubicin) were even more powerful. The best synergist was the benzophenanthridine alkaloid sanguinarine. It reduced the IC₅₀ value of doxorubicin 17.58-fold in two-drug combinations (sanguinarine + doxorubicin) and even 35.17-fold in three-drug combinations (sanguinarine + digitonin + doxorubicin) in Caco-2 cells. Thus synergistic drug combinations offer the possibility to enhance doxorubicin efficacy in chemotherapy.     

Facile synthesis of novel substituted aryl-thiazole (SAT) analogs via one-pot multi-component reaction as potent cytotoxic agents against cancer cell lines

In this study, twenty-five (25) substituted aryl thiazoles (SAT) 1–25 were synthesized, and their in vitro cytotoxicity was evaluated against four cancer cell lines, MCF-7 (ER^+ve breast), MDA-MB-231 (ER^−ve breast), HCT116 (colorectal) and HeLa (cervical). The activity was compared with the standard anticancer drug doxorubicin (IC₅₀ = 1.56 ± 0.05 μM). Among them, compounds 1, 4–8, and 19 were found to be toxic to all four cancer cell lines (IC₅₀ values 5.37 ± 0.56–46.72 ± 1.80 μM). Compound 20 was selectively active against MCF7 breast cancer cells with IC₅₀ of 40.21 ± 4.15 μM, whereas compound 19 was active against MCF7 and HeLa cells with IC₅₀ of 46.72 ± 1.8, and 19.86 ± 0.11 μM, respectively. These results suggest that substituted aryl thiazoles 1 and 4 deserve to be further investigated in vivo as anticancer leads.     

Development of doxorubicin loading platform based albumin-sporopollenin as drug carrier

Albumin is thought as an drug carrier for doxorubicin (DOX). The binding of doxorubicin to albumin was studied on the surface of sporopolleninin (SP) to produce a new drug system based natural materials. Human serum albumin (HSA) was immobilized on SPIONs in 20 mM Tris buffer, 7.4 of pH. Data showed that binding amount of HSA has been found to be as 285.53 µg to the 25 mg of Sporopolleninin which also bounded 319.76 µM of DOX. Binding of protein and drug to Sp were clarified by SEM, EDX and FT-IR analysis.     

Differential susceptibility of human primary aortic and coronary artery vascular cells to RNA interference

BackgroundRNAi technology is a promising tool for gene therapy of vascular disease. However, the biological heterogeneity between endothelial (EC) and vascular smooth muscle cells (SMC) and within different vascular beds make them differentially susceptible to siRNA. This is further complicated by the task of choosing the right transfection reagent that leads to consistent gene silencing across all cell types with minimal toxicity. The goal of this study was to investigate the intrinsic RNAi susceptibility of primary human aortic and coronary artery endothelial and vascular smooth muscle cells (AoEC, CoEC, AoSMC and CoSMC) using adherent cell cytometry.MethodsCells were seeded at a density of 5000 cells/well of a 96well plate. Twenty four hours later cells were transfected with either non-targeting unlabeled control siRNA (50 nM), or non-targeting red fluorescence labeled siRNA (siGLO Red, 5 or 50 nM) using no transfection reagent, HiPerFect or Lipofectamine RNAiMAX. Hoechst nuclei stain was used to label cells for counting. For data analysis an adherent cell cytometer, Celigo was used.ResultsRed fluorescence counts were normalized to the cell count. EC displayed a higher susceptibility towards siRNA delivery than SMC from the corresponding artery. CoSMC were more susceptible than AoSMC. In all cell types RNAiMAX was more potent compared to HiPerFect or no transfection reagent. However, after 24 h, RNAiMAX led to a significant cell loss in both AoEC and CoEC. None of the other transfection conditions led to a significant cell loss.ConclusionThis study confirms our prior observation that EC are more susceptible to siRNA than SMC based on intracellular siRNA delivery. RNAiMax treatment led to significant cell loss in AoEC and CoEC, but not in the SMC populations. Additionally, this study is the first to demonstrate that coronary SMC are more susceptible to siRNA than aortic SMC.     

Synthesis, characterization, and cytotoxicity in vitro of the complex [Mn (Hptc) (phen) (OH)] n

AimsA bridging ligand 2,4,6-pyridine tricarboxylic acid (H₃ptc) and its manganese(II) complex [Mn(Hptc)(phen)(OH)]n(Hptc = 2,4,6-pyridine tricarboxylic acid, phen = 1,10-phenanthroline) have been synthesized and characterized.Main methodsThe interaction with DNA (HeLa and KB) was carried out by fluorescence spectrum and gel electrophoresis assay. In vitro apoptosis assay and cytotoxicity assay detect the manganese (II) complex interaction with cancer cells.Key findingsFluorescence spectrum demonstrated the ability of the complexes to interact with DNA in an intercalative mode. Gel electrophoresis assay exhibited more effective DNA-cleavage activity. In vitro apoptosis assay of the complexes were examined on HeLa and KB cells, exhibited cytotoxic specificity and a significant cancer cell inhibitory rate.SignificanceThe complex may be a latent antitumor agent as a result of its unique interaction mode with DNA and cancer cells inhibition effect.     

Design of cyclic RGD-conjugated Aib-containing amphipathic helical peptides for targeted delivery of small interfering RNA

To achieve the targeted delivery of siRNA, five conjugates of Aib-containing amphipathic helical peptides with mono-, di-, and trivalent cRGDfC [cyclo(-Arg-Gly-Asp-d-Phe-Cys-)], which is known to bind to α_Vβ₃ integrin, at several positions of the amphipathic helical peptide were designed and synthesized. Among the five conjugates, the monovalent cRGDfC conjugating at position 20 of the amino acid sequence of the helical peptide through the formation of a disulfide bond (PI) and the divalent cRGDfC conjugating at positions 2 and 14 of the amino acid sequence of the helical peptide through the formation of disulfide bonds (PIII) significantly enhanced the delivery of fluorescence-labeled siRNA into A549 cells as the peptide/siRNA complex formed by electrostatic interaction. The cellular uptake of the PI/siRNA complex was mediated by both endocytic and non-endocytic pathways, whereas that of the PIII/siRNA complex was enabled by endocytosis. Furthermore, the cellular uptake of the PI/siRNA complex might involve specific interactions of the RGD group with the α_Vβ₃ integrin receptor. Next, the RNAi effect of the peptide/siRNA complex on luciferase expression in A549-Luc cells was examined. Luciferase expression was significantly decreased in the presence of the complex at the concentration of 1.0 μM PI/10 nM siRNA. In contrast, the PIII/siRNA complex did not show the RNAi effect under the same conditions. However, extending the incubation time led to the suppression of the luciferase expression in the presence of the PIII/siRNA complex. Considering that the cellular uptake of the PIII/siRNA complex is mediated by the endocytic pathway, the release of siRNA from the endosome into the cytosol might require a long time. We present herein a useful and unique tool for the delivery of siRNA.     

Intentional formation of a protein corona on nanoparticles: Serum concentration affects protein corona mass,surface charge,and nanoparticle–cell interaction

The protein corona, which immediately is formed after contact of nanoparticles and biological systems, plays a crucial role for the biological fate of nanoparticles. In the here presented study we describe a strategy to control the amount of corona proteins which bind on particle surface and the impact of such a protein corona on particle-cell interactions. For corona formation, polyethyleneimine (PEI) coated magnetic nanoparticles (MNP) were incubated in a medium consisting of fetal calf serum (FCS) and cell culture medium. To modulate the amount of proteins bind to particles, the composition of the incubation medium was varied with regard to the FCS content. The protein corona mass was estimated and the size distribution of the participating proteins was determined by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE). Additionally, the zeta potential of incubated particles was measured. Human blood–brain barrier-representing cell line HBMEC was used for in vitro incubation experiments. To investigate the consequences of the FCS dependent protein corona formation on the interaction of MNP and cells flow cytometry and laser scanning microscopy were used. Zeta potential as well as SDS–PAGE clearly reveal an increase in the amount of corona proteins on MNP with increasing amount of FCS in incubation medium. For MNP incubated with lower FCS concentrations especially medium-sized proteins of molecular weights between 30 kDa and 100 kDa could be found within the protein corona, whereas for MNP incubated within higher FCS concentrations the fraction of corona proteins of 30 kDa and less increased. The presence of the protein corona reduces the interaction of PEI-coated MNP with HBMEC cells within a 30 min-incubation.     

Molecular docking,a tool to determine interaction of CuO and TiO2 nanoparticles with human serum albumin

BackgroundWe study the human serum albumin (HSA) protein-CuO nanoparticle interaction to identify the specific binding site of protein with CuO nanoparticles by molecular docking and compared it with HSA-TiO₂ nanoparticle interaction.MethodsThe protein structural data that was obtained using Autodock 4.2.ResultsIn case of CuO np-HSA interaction, the distances from the centre of Subdomain IIIA to Arg-472 is 2.113 Å and Lys 475, Glu 492, Ala 490, Cys 487, Ala 490 are the bound neighbouring residues with Lys 475, Glu 492 at aliphatic region. The binding energy generated was ?1.64 kcal mol^?1. However, for TiO₂ nanoparticle, the binding region is surrounded by Arg 257, Ala 258, Ser 287, His 288, Leu 283, Ala 254, Tyr 150 (subdomain II A) as neighbouring residue. Moreover, Glu 285, Lys 286 forms aliphatic grove for TiO₂-HSA, Ser-287 at the centre region form hydrogen bond with nanoparticle and Leu 283, Leu 284 forming hydrophopobic grove for TiO₂ nanoparticle-HSA interaction. The binding energy generated was ?2.47 kcal mol^?1.ConclusionsAnalysis suggests that CuO bind to suldow site II i.e subdomain III A of HSA protein where as TiO₂ nanoparticle bind to suldow site I i.e subdomain IIA of HSA protein.General significanceThe structural information that derives from this study for CuO and TiO₂ nanoparticles may be useful in terms of both high and low-affinity binding sites when designing these nanoparticles based drugs delivery system.     

The effect of prehydrolysis and improved mixing on high-solids batch simultaneous saccharification and fermentation of spruce to ethanol

In the production of ethanol from lignocellulosic material, it is necessary to reach a high ethanol concentration after fermentation. Simply increasing the substrate concentration leads to stirring problems and inhibition of the enzymes and yeast in the process.Batch simultaneous saccharification and fermentation (SSF) of steam-pretreated spruce with 13.7% water-insoluble solids (WIS) (25% total solids (TS)) was run in a stirred-tank reactor as well as in two reactors designed to handle solid or semi-solid material. In all reactors, the overall ethanol yields were only between 5 and 6%. Fermentation of the liquid fraction of the steam-pretreated spruce slurry resulted in an overall ethanol yield of 85%.22 h of prehydrolysis at 48 °C prior to SSF at 32 °C significantly increased the overall ethanol yield to 72% (final ethanol concentration of 47.8 g/L), using the whole slurry of steam-pretreated spruce at a dry matter content of 13.7% WIS (25% TS).     

Cytotoxic effect of Green synthesized silver nanoparticles using Melia azedarach against in vitro HeLa cell lines and lymphoma mice model

This communication explains the biosynthesis of stable silver nanoparticles (AgNPs) from Melia azedarach and its cytotoxicity against in vitro HeLa cells and in vivo Dalton's ascites lymphoma (DAL) mice model. The AgNPs synthesis was determined by UV–visible spectrum and it was further characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS) and X-ray diffraction (XRD) analysis. Zeta potential analysis revealed stable AgNPs at ?24.9 mV. UV visible spectrum indicated an absorption peak at 436 nm which reflects its specific Surface Plasmon Resonance (SPR). Biosynthesized AgNPs were predominantly cubical and spherical with an average particle size of 78 nm approximately as observed through SEM and DLS analysis, respectively. Cytotoxicity of biosynthesized AgNPs against in vitro Human epithelial carcinoma cell line (HeLa) showed a dose–response activity. Lethal dose (LD₅₀) value was found to be 300 μg/mL of AgNPs against HeLa cell line. Cytotoxicity against normal continuous cell line human breast lactating, donor 100 (HBL 100) was found only in increased concentration of both AgNPs and 5-FU. In addition, in vivo DAL mice model showed significant increase in life span, induction of apoptosis was evidenced by acridine orange and ethidium bromide (AO and EB) staining.     

Silver glyconanoparticles functionalized with sugars of sweet sorghum syrup as an antimicrobial agent

Bio-directed synthesis of metal nanoparticles is gaining importance due to their biocompatibility, low toxicity and eco-friendly nature. We used sweet sorghum syrup for a facile and cost-effective green synthesis of silver glyconanoparticles. Silver nanoparticles were formed due to reduction of silver ions when silver nitrate solution was treated with sorghum syrup solutions of different pH values. The nanoparticles were characterized by UV–vis, TEM (transmission electron microscopy), DLS (dynamic light scattering), EDAX (energy dispersive X-ray spectroscopy), FT-IR (fourier transform infrared spectroscopy) and XRD (X-ray diffraction spectroscopy). The silver glyconanoparticles exhibited a characteristic surface plasmon resonance around 385 nm. At pH 8.5, the nanoparticles were mono-dispersed and spherical in shape with average particle size of 11.2 nm. The XRD and SAED studies suggested that the nanoparticles were crystalline in nature. EDAX analysis showed the presence of elemental silver signal in the synthesized glyconanoparticles. FT-IR analysis revealed that glucose, fructose and sucrose present in sorghum syrup acted as capping ligands. Silver glyconanoparticles prepared at pH 8.5 had a zeta potential of ?28.9 mV and were anionic charged. They exhibited strong antimicrobial activity against Gram-positive, Gram-negative and different Candida species at MIC values ranging between 2 and 32 μg ml^?1. This is first report on sweet sorghum syrup sugars-derived silver glyconanoparticles with antimicrobial property.     

C8-glycosphingolipids preferentially insert into tumor cell membranes and promote chemotherapeutic drug uptake

Insufficient drug delivery into tumor cells limits the therapeutic efficacy of chemotherapy. Co-delivery of liposome-encapsulated drug and synthetic short-chain glycosphingolipids (SC-GSLs) significantly improved drug bioavailability by enhancing intracellular drug uptake. Investigating the mechanisms underlying this SC-GSL-mediated drug uptake enhancement is the aim of this study. Fluorescence microscopy was used to visualize the cell membrane lipid transfer intracellular fate of fluorescently labeled C₆-NBD-GalCer incorporated in liposomes in tumor and non-tumor cells. Additionally click chemistry was applied to image and quantify native SC-GSLs in tumor and non-tumor cell membranes. SC-GSL-mediated flip-flop was investigated in model membranes to confirm membrane-incorporation of SC-GSL and its effect on membrane remodeling. SC-GSL enriched liposomes containing doxorubicin (Dox) were incubated at 4 °C and 37 °C and intracellular drug uptake was studied in comparison to standard liposomes and free Dox.SC-GSL transfer to the cell membrane was independent of liposomal uptake and the majority of the transferred lipid remained in the plasma membrane. The transfer of SC-GSL was tumor cell-specific and induced membrane rearrangement as evidenced by a transbilayer flip-flop of pyrene-SM. However, pore formation was measured, as leakage of hydrophilic fluorescent probes was not observed. Moreover, drug uptake appeared to be mediated by SC-GSLs. SC-GSLs enhanced the interaction of doxorubicin (Dox) with the outer leaflet of the plasma membrane of tumor cells at 4 °C. Our results demonstrate that SC-GSLs preferentially insert into tumor cell plasma membranes enhancing cell intrinsic capacity to translocate amphiphilic drugs such as Dox across the membrane via a biophysical process.