Agnieszka Z. Wilczewska

Nanoparticles as drug delivery systems

Controlled drug delivery systems (DDS) have several advantages compared to the traditional forms of drugs. A drug is transported to the place of action, hence, its influence on vital tissues and undesirable side effects can be minimized. Accumulation of therapeutic compounds in the target site increases and, consequently, the required doses of drugs are lower. This modern form of therapy is especially important when there is a discrepancy between the dose or the concentration of a drug and its therapeutic results or toxic effects. Cell-specific targeting can be accomplished by attaching drugs to specially designed carriers. Various nanostructures, including liposomes, polymers, dendrimers, silicon or carbon materials, and magnetic nanoparticles, have been tested as carriers in drug delivery systems. In this review, the aforementioned nanocarriers and their connections with drugs are analyzed. Special attention is paid to the functionalization of magnetic nanoparticles as carriers in DDS. Then, the advantages and disadvantages of using magnetic nanoparticles as DDS are discussed.

Magnetic nanoparticles as new diagnostic tools in medicine

Magnetic iron oxide nanoparticles have raised much interest during the recent years due to their novel properties (superparamagnetism, high saturation field, blocking temperature, etc.) and potential applications in organic synthesis, biotechnology and finally in medicine. The medicinal applications include: controlled drug delivery systems (DDS), magnetic resonance imaging (MRI), magnetic fluid hyperthermia (MFH), macromolecules and pathogens separation, cancer therapy and so on. In this paper we would like to present the newest literature reports concerning usage of MNPs in medicinal diagnostics such as: - magnetic separations of DNA (immobilization, isolation, diagnosis of genetic disorders and detection of exogenous substances in the organisms) - magnetic immobilization of proteins (applications in biotechnology, medicine, and catalysis) - magnetic separations of pathogens (i.e. isolation of bacteria, detection of various pathogens) - magnetic resonance imaging (imaging contrast agents, lymphangiography).

Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles

BackgroundCeragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. However, in some settings their strong bactericidal activity is associated with toxicity towards host cells. To modulate ceragenin CSA-13 antibacterial activity and biocompatibility, CSA-13-coated magnetic nanoparticles (MNP-CSA-13) were synthesized. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize MNP-CSA-13 physicochemical properties. Bactericidal action and ability of these new compounds to prevent Pseudomonas. aeruginosa biofilm formation were assessed using a bacteria killing assay and crystal violet staining, respectively. Release of hemoglobin from human red blood cells was measured to evaluate MNP-CSA-13 hemolytic activity. In addition, we used surface activity measurements to monitor CSA-13 release from the MNP shell. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity.ResultsOur studies revealed that the MNP-CSA-13 nanosystem is stable and may be used as a pH control system to release CSA-13. MNP-CSA-13 exhibits strong antibacterial activity, and the ability to prevent bacteria biofilm formation in different body fluids. Additionally, a significant decrease in CSA-13 hemolytic activity was observed when the molecule was immobilized on the nanoparticle surface.ConclusionOur results demonstrate that CSA-13 retains bactericidal activity when immobilized on a MNP while biocompatibility increases when CSA-13 is covalently attached to the nanoparticle.

Separation of ruthenium from environmental samples on polymeric sorbent based on imprinted Ru(III)-allyl acetoacetate complex

A new ion imprinted polymer (IIP) for ruthenium recognition/pre-concentration was prepared via bulk polymerization using methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross-linking agent in the presence of Ru(III)-allyl acetoacetate complex as a template. The synthesized IIP was used as a new support for solid phase extraction (SPE) of ruthenium from environmental samples before electrothermal atomic absorption spectrometric determination. Variables affecting the SPE process, such as pH, load and elution flow rates, as well as concentration and volume of the eluting solution, were evaluated. The optimized procedure consists of a sample loading (sample pH of 6.5 ± 0.5) through IIP-SPE columns containing 200mg of the synthesized IIP at a flow rate of 1.0 mL min(-1). Elution was performed by passing 0.3 mol L(-1) thiourea in 0.1 mol L(-1) HCl at a flow rate of 1.0 mL min(-1). For 10 mL of sample pre-concentration factor of 20 was achieved. The limit of detection of the method was 0.32 ng mL(-1), while the relative standard deviation for six replicated separation processes was 2.5%. Good selectivity of the synthesized material for Ru(III) ions against other transition metal ions assures efficient removal of matrix of analyzed samples (tap and river water, municipal and road sewages, and grass) by the proposed IIP-SPE procedure.

Magnetic nanoparticles as a drug delivery system that enhance fungicidal activity of polyene antibiotics

This study was designed to assess the antifungal/anti-biofilm and hemolytic properties of two polyene antibiotics, amphotericin B (AMF) and nystatin (NYS), attached to the surface of magnetic nanoparticles (MNP) against clinical isolates of Candida species and human red blood cells, respectively. The developed nanosystems, MNP@AMF and MNP@NYS, displayed stronger fungicidal activity than unbound AMF or NYS. Synergistic activity was observed with a combination of polyenes and MNPs against all tested Candida strains. Nanosystems were more potent than unbound agents when tested against Candida strains in the presence of pus, and as agents able to prevent Candida biofilm formation. The observed inactivation of catalase Cat1 in Candida cells upon treatment with the nanosystems suggests that disruption of the oxidation-reduction balance is a mechanism leading to inhibition of Candida growth. The significant decrease of polyenes lytic activity against host cells after their attachment to MNPs surface indicates improvement in their biocompatibility.

Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells

The pleiotropic activity of human cathelicidin LL-37 peptide includes an ability to suppress development of colon cancer cells. We hypothesized that the anticancer activity of LL-37 would improve when attached to the surface of magnetic nanoparticles (MNPs). Using colon cancer culture (DLD-1 cells and HT-29 cells), we evaluated the effects of MNPs, LL-37 peptide, its synthetic analog ceragenin CSA-13, and two novel nanosystems, ie, MNP@LL-37 and MNP@CSA-13, on cancer cell viability and apoptosis. Treatment of cancer cells with the LL-37 peptide linked to MNPs (MNP@LL-37) caused a greater decrease in cell viability and a higher rate of apoptosis compared with treatment using free LL-37 peptide. Additionally, we observed a strong ability of ceragenin CSA-13 and MNP@CSA-13 to induce apoptosis of DLD-1 cells. We found that both nanosystems were successfully internalized by HT-29 cells, and cathelicidin LL-37 and ceragenin CSA-13 might play a key role as novel homing molecules. These results indicate that the previously described anticancer activity of LL-37 peptide against colon cancer cells might be significantly improved using a theranostic approach.

Growth arrest and rapid capture of select pathogens following magnetic nanoparticle treatment.

Thorough understanding of magnetic nanoparticle (MNP) properties is essential for developing new theranostics. In this study, we provide evidence that non-modified magnetic iron oxide nanoparticles and their functionalized derivatives may be used to restrict growth and capture different pathogens. Coprecipitation of Fe(2+) and Fe(3+) ions in an alkaline solution was used to synthesize MNPs that subsequently were functionalized by gold and aminosilane coating. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were used to assess their physicochemical properties. A significant decrease of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans outgrown from medium after addition of MNPs or their derivatives was observed during 24h culture. Measurement of optical density revealed that using MNPs, these pathogens can be quickly captured and removed (with efficiency reaching almost 100%) from purposely infected saline buffer and body fluids such as human blood plasma, serum, abdominal fluids and cerebrospinal fluids. These effects depend on nanoparticle concentration, surface chemistry, the type of pathogen, as well as the surrounding environment.

Gold-functionalized magnetic nanoparticles restrict growth of Pseudomonas aeruginosa

Superparamagnetic iron oxide nanoparticles (SPIONs) and their derivatives (aminosilane and gold-coated) have been widely investigated in numerous medical applications, including their potential to act as antibacterial drug carriers that may penetrate into bacteria cells and biofilm mass. Pseudomonas aeruginosa is a frequent cause of infection in hospitalized patients, and significant numbers of currently isolated clinical strains are resistant to standard antibiotic therapy. Here we describe the impact of three types of SPIONs on the growth of P. aeruginosa during long-term bacterial culture. Their size, structure, and physicochemical properties were determined using transmission electron microscopy, X-ray diffraction analysis, and Fourier transform infrared spectroscopy. We observed significant inhibition of P. aeruginosa growth in bacterial cultures continued over 96 hours in the presence of gold-functionalized nanoparticles (Fe3O4@Au). At the 48-hour time point, growth of P. aeruginosa, as assessed by the number of colonies grown from treated samples, showed the highest inhibition (decreased by 40%). These data provide strong evidence that Fe3O4@Au can dramatically reduce growth of P. aeruginosa and provide a platform for further study of the antibacterial activity of this nanomaterial.

STM‐Based Molecular Junction of Carbon Nano‐Onion

was almost concurrent with that of the CNTs, progress in thisfield has been very slow. Our current research has been cen-tered mainly on carbon-based materials, such as CNOs, whichrepresent a structural link between the fullerenes and themulti-wall carbon nanotubes. The CNO structures consist ofa hollow spherical fullerene core surrounded by concentric andcurved graphene layers with increasing diameters. The dis-tance between the layers is very close to the interlayer dis-tance in bulk graphite (0.34 nm).

A practical process for polymer-supported synthesis

Abstract Various complex structures can be attached to a polystyrene oligomer using the simple but powerful xanthate transfer technology; the material obtained is soluble in many of the common organic solvents allowing further reactions under homogeneous conditions, but can be precipitated with methanol making this technique especially suitable for conducting parallel syntheses.