Previous studies have shown that magnetic nanoparticles possess great potential for various
in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, cancer ...treatment agents, and controlled drug delivery. Many of these applications require that magnetic nanoparticles be colloidally stable in biological media. The goal of this study was to obtain a magnetic fluid produced by the colloidal suspension of manganese/zinc ferrite (MZF) nanoparticles that could be stably dispersed in aqueous solution throughout the range of physiological pH and ionic strength. These superparamagnetic nanoparticles were stabilized through steric repulsion by coating with biologically compatible carboxymethyl dextran (CMDx). Samples of the resultant magnetic fluid were analyzed using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), X-ray diffraction (XRD), zeta potential measurements, dynamic light scattering, transmission electron microscopy (TEM), and SQUID magnetometry. Results show that we obtained superparamagnetic metal-oxide crystals with composition of Mn
0.24Zn
0.76Fe
2O
4. Cell viability measurements show the material is non-toxic to MCF-7 and CaCo-2 cell lines at concentrations of up to 7.5
mg/mL of particle fraction for contact time of up to 48
h.
•AgNPs–CMD were preparated from of AgNO3 and CMD in mole ratio 1:1 and 1:2.•AgNPs–CMD were characterization by (UV–VIS, SEM, XRD, GPC, FT-IR).•The crystalline structures of AgNPs–CMD were found to be ...face centered cubic type.•The AgNPs–CMD showed strong antibacterial and antifungal activity.
Silver nanoparticles (AgNPs–CMD) were synthesized from aqueous solution of silver nitrate (AgNO3) and carboxymethyl dextrane (CMD) in mole ratio 1:1 and 1:2. The characterization of AgNPs–CMD was performed by ultraviolet–visible (UV–VIS) spectroscopy, gel permeation chromatography (GPC), scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and antimicrobial activity. The formation of AgNPs–CMD was screened by color changes of the reaction mixture to yellow, by measuring the surface plasmon resonance absorption peak in UV–VIS region at 420nm. The GPC chromatography measurement confirmed the formation of AgNPs–CMD. The SEM microscopy was used for size and shape of AgNPs–CMD nanoparticles determination. The presence of elemental silver and crystalline structure of AgNPs–CMD were confirmed by XRD analyses. The possible functional group of CMD responsible for the reduction and stabilization of AgNPs were determinated by FT-IR spectroscopy. The AgNPs–CMD showed strong antibacterial activity against Bacillus lutea, Bacillus aureus, Bacillus cereus, Enterococus fecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae and antifungal activity against Aspergillus spp., Penicillum spp., and Candida albicans.
Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse ...effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy.
The present work discusses a detailed study of the fabrication steps of carboxymethyl-dextran SPR sensor chips with specal focus on the effect of dextran molecular weight (40, 200, and 500 kDa) both ...on the chip physical characteristics after each fabrication step and on toxin detection performance. Physical characterization was performed using ATR-FTIR, AFM, profilometry, and surface plasmon resonance (SPR) as analytical methods. Based on ATR-FTIR spectroscopy analysis, it is demonstrated that NaOH concentration plays a critical role in the epichlorohydrin (ECH) activation step for subsequent dextran molecules covalent bonding and should be less than 0.4 M, preferably 0.2 M. This is in contrast to the concentration of 0.4 M used in conventional protocols. After covalent binding of the monoclonal anti-staphylococcal enterotoxin B (anti-SEB) to the carboxyl groups of dextran matrix, the detection of enterotoxin B as a function of dextran molecular weight has been assessed. Dextran with a molecular weight of 200 kDa results in a distinct larger SPR angle shift of the final chip with respect to 40 and 500 kDa molecular weights. This observation is explained based on the SPR theory and the physico-chemical characteristics of the antibody/dextran layers measured throughout this study. The SPR sensor chip with the dextran molecular weight of 200 kDa may be considered as an appropriate candidate for the detection of proteins with the same molecular weight as enterotoxin B.
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To improve the anti-tumor activity of EGFR2R-lytic hybrid peptide, we prepared peptide-modified dextran conjugates with the disulfide bonds between thiolated carboxymethyl dextran ...(CMD-Cys) and cysteine-conjugated peptide (EGFR2R-lytic-Cys). In vitro release studies showed that the peptide was released from the CMD-s-s-peptide conjugate in a concentration-dependent manner in the presence of glutathione (GSH, 2μM–2mM). The CMD-s-s-peptide conjugate exhibited a similar cytotoxic activity with free peptide alone against human pancreatic cancer BxPC-3 cells in vitro. Furthermore, it was shown that the CMD-s-s-peptide conjugates were highly accumulated in tumor tissue in a mouse xenograft model using BxPC-3 cells, and the anti-tumor activity of the conjugate was more effective than that of the free peptide. In addition, the plasma concentrations of peptide were moderately increased and the elimination half-life of the peptide was prolonged after intravenous injection of CMD-s-s-peptide conjugates. These results demonstrated that the conjugate based on thiolated CMD polymer would be potentially useful carriers for the sustained release of the hybrid peptide in vivo.
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► A new RIfS-based label-free biosensing system for C-reactive protein was developed. ► Silicon-based inexpensive chips and the simple optical setup were employed. ► Owing to the TMS ...treatment and the use of protein A, the sensitivity was enhanced. ► It can be applied to other target as a substitute of SPR-based expensive sensors.
Reflectometric interference spectroscopy (RIfS) is a label-free, time-resolved technique, and suitable for detecting antibody–antigen interaction. This work describes a continuous flow biosensor for C-reactive protein (CRP), involving an effective immobilization method of a monoclonal antibody against CRP (anti-CRP) to achieve highly sensitive RIfS-based detection of CRP. The silicon nitride-coated silicon chip (SiN chip) for the RIfS sensing was first treated with trimethylsilylchloride (TMS), followed by UV-light irradiation to in situ generation of homogeneous silanols on the surface. Following amination by 3-aminopropyltriethoxysilane, carboxymethyldextran (CMD) was grafted, and subsequently, protein A was immobilized to create the oriented anti-CRP surface. The immobilization process of protein A and anti-CRP was monitored with the RIfS system by consecutive injections of an amine coupling reagent, protein A and anti-CRP, respectively, to confirm the progress of each step in real time. The sensitivity was enhanced when all of the processes were adopted, suggesting that the oriented immobilization of anti-CRP via protein A that was coupled with the grafted CMD on the aminated surface of TMS-treated SiN chip. The feasibility of the present sensing system was demonstrated on the detection of CRP, where the silicon-based inexpensive chips and the simple optical setup were employed. It can be applied to other target molecules in various fields of life science as a substitute of surface plasmon resonance-based expensive sensors.
The carboxymethyl dextran-y-cyclodextrin (CMD-yCD) conjugate was prepared as the carrier for the delivery of the poorly water-soluble anticancer drug, doxorubicin (DOX). The conjugate could form ...self-assembled nanoparticles (315 nm in diameter) in an aqueous solution, which might be due to the hydrogen bonding among yCD molecules in the conjugate. DOX was effectively encapsulated into CMD-yCD nanoparticles (CMD-NPs) by the emulsion method. In particular, regardless of the feed amount of DOX, its loading efficiencies were always greater than 70%. CMD-NPs released DOX in a sustained manner, owing to the inclusion complex formation between DOX and yCD. When Cy5.5-labeled CMD-NPs were treated with SCC7 cancer cells, strong fluorescence signals were observed at the cytosol, indicating effective intracellular uptake. In addition, DOX-loaded CMD-NPs exhibited dose-dependent cytotoxicity to SCC7 cancer cells. However, the empty nanoparticles did not show toxicity to the cells, implying their high biocompatibility. Overall, these results suggest that the CMD-gammaCD conjugate could be a useful carrier for the delivery of DOX.
Antigen-specific cytotoxic T lymphocytes (CTLs), which eliminate target cells bearing antigenic peptides presented by surface major histocompatibility complex (MHC) class I molecules, play a key role ...in cancer immunotherapy. However, the majority of tumors are not immunologically rejected since they express self-antigens which are not recognized by CTLs as foreign. To foreignize these tumors for CTL-mediated immunological rejection, it is essential to develop carriers that can effectively deliver foreign antigens to cancer cells.
A polymeric conjugate, composed of a carboxymethyl dextran (CMD) as the backbone and ovalbumin (OVA) as a model foreign antigen, was prepared to investigate its potential as the antigen carrier for cancer immunotherapy.
An in vitro cellular uptake study showed that the conjugate was successfully taken up by TC-1 cervical cancer cells. When CMD-OVA was systemically administered to tumor-bearing mice, the strong fluorescence signal was observed at the tumor site over the whole period of time period, suggesting high tumor targetability of the conjugate. Compared to free OVA, CMD-OVA induced significantly higher antigen presentation at the tumor site.
The CMD-OVA conjugate can effectively deliver the antigen to the tumor site, implying its high potential as the antigen carrier for cancer immunotherapy.
It was the aim of this study to develop a sustained parenteral peptide (DALCE) delivery system by the immobilization of DALCE to thiolated carboxymethyl dextran-cysteine (CMD-Cys) via disulfide bond ...formation. The resulting CMD-Cys–DALCE conjugate displayed a 22.6±7.9% (m/m) of DALCE (mean±S.D.; n=3). The conjugation of DALCE with CMD-Cys was confirmed by FTIR-ATR spectroscopy. In vitro release studies of conjugate CMD-Cys–DALCE in the presence of 2μM/ml reduced glutathione (GSH) being also available in the plasma showed a sustained peptide release over a time period of 8h, because of thiol/disulfide exchange reactions. For in vivo pharmacokinetic study, DALCE and CMD-Cys–DALCE were administered intravenously to male Sprague–Dawley rats at a dose of 1mg/kg. The AUC0-8 (ng.min/ml) was determined to be 268848±924 and 40019±495 for CMD-Cys–DALCE and DALCE, respectively. The mean residence time (MRT) was determined to be 256±8 and 53.1±9.5min for CMD-Cys–DALCE and for DALCE, respectively. CMD-Cys–DALCE showed a more than 5-fold increased elimination half-life (p<0.01), 3-fold decreased volume of distribution (p<0.01) and a 6.7-fold decreased plasma clearance rate (p<0.01) compared to DALCE. According to these findings, CMD-Cys–DALCE seems to act as prodrug by improving half-life and decreasing plasma clearance.
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The copper(II) ion complexes with carboxymethyl dextran (CMD) and dextran sulfate (DS) were studied by different methods. Content of copper was determined by atomic absorption spectroscopy. It was ...found that copper : ligand mole ratio (Cu : CMD) is 1 : 2, and Cu : DS is 1 : 1 by mole ratio method. Spectrophotometric parameters of synthesized compounds are characteristic for Cu(II) ion in octahedral (
O
h
) coordination. Analyzing of FTIR spectra in ν(C=O) vibration region has showed that -COOH group acts as bidentate ligand, while the compounds of Cu(II) with DS copper ions are in the region of four oxygen atoms of two adjacent sulfo groups. The presence of crystalline water was determined by isotopic substitution of H
2
O molecules with D
2
O molecules. Comparison of spectra recorded at room (RT) and liquid nitrogen temperature (LNT) has enabled detection bands of water molecules libration indicating that they are coordinated complementing coordination sphere of Cu(II) ions to six. The complexes are of Cu(II) · (CMD)
2
· (H
2
O)
2
or Cu(II) · DS · (H
2
O)
2
type. The similarities of the γ(C-H) range in a part of FTIR spectra indicate that there is no difference in the conformation of the
4
C
1
glucopyranose (Glc) unit CMD and DS synthesized Cu(II) complexes.
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