Magnetoliposomes based on manganese ferrite nanoparticles as nanocarriers for antitumor drugs

Manganese ferrite nanoparticles with a size distribution of 26 ± 7 nm (from TEM measurements) were synthesized by the coprecipitation method. The obtained nanoparticles exhibit a superparamagnetic behaviour at room temperature with a magnetic squareness of 0.016 and a coercivity field of 6.3 Oe. These nanoparticles were either entrapped in liposomes (aqueous magnetoliposomes, AMLs) or covered with a lipid bilayer, forming solid magnetoliposomes (SMLs). Both types of magnetoliposomes, exhibiting sizes below or around 150 nm, were found to be suitable for biomedical applications. Membrane fusion between magnetoliposomes (both AMLS and SMLs) and GUVs (giant unilamellar vesicles), the latter used as models of cell membranes, was confirmed by F¨orster Resonance Energy Transfer (FRET) assays, using a NBD labeled lipid as the energy donor and Nile Red or rhodamine B-DOPE as the energy acceptor. A potential antitumor thienopyridine derivative was successfully incorporated into both aqueous and solid magnetoliposomes, pointing to a promising application of these systems in oncological therapy, simultaneously as hyperthermia agents and nanocarriers for antitumor drugs.

Magnetoliposomes based on manganese ferrite nanoparticles as nanocarriers for antitumor drugs

Publicado em "NanoPT2016 book of abstracts"

Tailored magnetic and magnetoelectric responses of polymer-based composites

The manipulation of electric ordering with applied magnetic fields has been realized on magnetoelectric (ME) materials, however, their ME switching is often accompanied by significant hysteresis and coercivity that represents, for some applications, a severe weakness. To overcome this obstacle, this work focus on the development of a new type of ME polymer nanocomposites that exhibits tailored ME response at room temperature. The multiferroic nanocomposites are based on three different ferrite nanoparticles, Zn0.2Mn0.8Fe2O4 (ZMFO), CoFe2O4 (CFO) and Fe3O4 (FO), dispersed in a piezoelectric co-polymer poly(vinylindene fluoride-trifluoroethylene), P(VDF-TrFE), matrix. No substantial differences were detected on the time-stable piezoelectric response of the composites (≈ -28 pC.N−1) with distinct ferrite fillers and for the same ferrite content of 10wt.%. Magnetic hysteresis loops from pure ferrite nanopowders showed different magnetic responses. ME results of the nanocomposite films with 10wt.% ferrite content revealed that the ME induced voltage increases with increasing DC magnetic field until a maximum of 6.5 mV∙cm−1∙Oe−1, at an optimum magnetic field of 0.26 T, and 0.8 mV∙cm−1∙Oe−1, at an optimum magnetic field of 0.15T, for the CFO/P(VDF-TrFE) and FO/P(VDF-TrFE) composites, respectively. On the contrary, the ME response of the ZMFO/P(VDF-TrFE) exposed no hysteresis and high dependence on the ZMFO filler content. Possible innovative applications such as memories and information storage, signal processing, ME sensors and oscillators have been addressed for such ferrite/PVDF nanocomposites.

Dielectric relaxation and ferromagnetic resonance in magnetoelectric (Polyvinylidene-fluoride)/ferrite composites

In this work the dielectric properties and ferromagnetic resonance of Polyvinylidene- uoride embedded with 10 wt. % of NiFe2O4 or Ni0.5Zn0.5Fe2O4 nanoparticles are presented. The mechanisms of the dielectric relaxation in these two composites do not differ from each other. For more precise characterization of the dielectric relaxation, a two dimensional distribution of relaxation times was calculated from the temperature dependencies of the complex dielectric permittivity. The results obtained from the 2D distribution and the mean relaxation time are found to be consistent. The dynamics of the dielectric permittivity is described by the Arrhenius law. The energy and attempt time of the dielectric relaxators lie in a narrow energy and time region thus proving that the single type chains of polymer are responsible for a dispersion. The magnetic properties of the composites were investigated using the fer- romagnetic resonance. A single resonance line was observed for both samples. From the temperature dependence (100 K - 310 K) of the resonance eld and linewidth, the origin of the observed line was attributed to the NiFe2O4 and Ni0.5Zn0.5Fe2O4 superparamagnetic nanoparticles. By measuring lms at dif- ferent orientations with respect to the external magnetic eld, the angular dependence of the resonance was observed, indicating the magnetic dipolar in-plane interactions.

Silica nanoparticles as dexamethasone delivery systems able to induce the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Bioactive glasses, especially silica-based materials, are reported to pres- ent osteoconductive and osteoinductive properties, fundamental char- acteristics in bone regeneration [1,2]. Additionally, dexamethasone (Dex) is one of the bioactive agents able to induce the osteogenic differ- entiation of mesenchymal stem cells by increasing the alkaline phos- phatase activity, and the expression levels of Osteocalcin and Bone Sialoprotein [3]. Herein, we synthesised silica (SiO2) nanoparticles (that present inherent bioactivity and ability to act as a sustained drug delivery system), and coated their surface using poly-L-lysine (PLL) and hyaluronic acid (HA) using the layer-by-layer processing technique. Further on, we studied the influence of these new SiO2-polyelectrolyte coated nanoparticles as Dex sustained delivery systems. The SiO2 nanoparticles were loaded with Dex (SiO2-Dex) and coated with PLL and HA (SiO2-Dex-PLL-HA). Their Dex release profile was evaluated and a more sustained release was obtained with the SiO2-Dex-PLL-HA. All the particles were cultured with human bone marrow-derived mes- enchymal stem cells (hBMSCs) under osteogenic differentiation culture conditions. hBMSCs adhered, proliferated and differentiated towards the osteogenic lineage in the presence of SiO2 (DLS 174nm), SiO2-Dex (DLS 175nm) and SiO2-Dex-PLL-HA (DLS 679nm). The presence of these materials induced the overexpression of osteogenic transcripts, namely of Osteocalcin, Bone Sialoprotein and Runx2. Scanning Elec- tron Microscopy/Electron Dispersive Spectroscopy analysis demon- strated that hBMSCs synthesised calcium phosphates when cultured with SiO2-Dex and SiO2-Dex-PLL-HA nanoparticles. These results indi- cate the potential use of these SiO2-polyelectrolytes coated nanoparti- cles as dexamethasone delivery systems capable of promoting osteogenic differentiation of hBMSCs.

Systematic design analysis and risk management on engineered nanoparticles occupational exposure

The production of nanotechnology-based products is increasing, along with the conscience of the possible harmful effects of some nanomaterials. The “safety-by-design” approaches are getting attention as helpful tools to develop safer products and production processes. The Systematic Design Analysis Approach could help to identify the solutions to control the workplace risks by defining the emission and exposure scenarios and the possible barriers to interrupt them. By applying this approach in a photocatalytic ceramic tiles development project it was possible to identify relevant nanoparticles emission scenarios and related barriers, and defining possible ways to reduce it.

Mechanism of extracellular silver nanoparticles synthesis by Stereum hirsutum and Fusarium oxysporum

The increasing interest for greener and biological methods of synthesis has led to the development of non-toxic and comparatively more bioactive nanoparticles. Unlike physical and chemical methods of nanoparticle synthesis, microbial synthesis in general and mycosynthesis in particular is cost-effective and environment-friendly. However, different aspects, such as the rate of synthesis, monodispersity and downstream processing, need to be improved. Many fungal-based mechanisms have been proposed for the formation of silver nanoparticles (AgNPs), mainly those involving the presence of nitrate reductase, which has been detected in filtered fungus cell used for AgNPs production. There is a general acceptance that nitrate reductase is the main responsible for the reduction of Ag ions for the formation of AgNPs. However, this generally accepted mechanism for fungal AgNPs production is not totally understood. In order to elucidate the molecules participating in the mechanistic formation of metal nanoparticles, the current study is focused on the enzymes and other organic compounds involved in the biosynthesis of AgNPs. The use of each free fungal mycelium of both Stereum hirsutum and Fusarium oxysporum will be assessed. In order to identify defective mutants on the nitrate reductase structural gene niaD, fungal cultures of S.hirsutum and F.oxysporum will be selected by chlorate resistance. In addition, in order to verify if each compound identified as key-molecule influenced on the production of nanoparticles, an in vitro assay using different nitrogen sources will be developed. Lately, fungal extracellular enzymes will be measured and an in vitro assay will be done. Finally, The nanoparticle formation and its characterization will be evaluated by UV-visible spectroscopy, electron microscopy (TEM), X-ray diffraction analysis (XRD), Fourier transforms infrared spectroscopy (FTIR), and LC-MS/MS.

Determination of the magnetostrictive response of nanoparticles via magnetoelectric measurements

It is successfully demonstrated that nanoparticle’s magnetostriction can be accurately determined based on the magnetoelectric effect measured on polymeric-composite materials. This represents a novel, simple and versatile method for the determination of particle’s magnetostriction at their nano-sized and dispersed state, which is, up to date, a difficult and imprecise task.

Thin films composed of gold nanoparticles dispersed in a dielectric matrix: the influence of the host matrix on the optical and mechanical responses

Gold nanoparticles were dispersed in two different dielectric matrices, TiO2 and Al2O3, using magnetron sputtering and a post-deposition annealing treatment. The main goal of the present work was to study how the two different host dielectric matrices, and the resulting microstructure evolution (including both the nanoparticles and the host matrix itself) promoted by thermal annealing, influenced the physical properties of the films. In particular, the structure and morphology of the nanocomposites were correlated with the optical response of the thin films, namely their localized surface plasmon resonance (LSPR) characteristics. Furthermore, and in order to scan the future application of the two thin film system in different types of sensors (namely biological ones), their functional behaviour (hardness and Young's modulus change) was also evaluated. Despite the similar Au concentrations in both matrices (~ 11 at.%), very different microstructural features were observed, which were found to depend strongly on the annealing temperature. The main structural differences included: (i) the early crystallization of the TiO2 host matrix, while the Al2O3 one remained amorphous up to 800 °C; (ii) different grain size evolution behaviours with the annealing temperature, namely an almost linear increase for the Au:TiO2 system (from 3 to 11 nm), and the approximately constant values observed in the Au:Al2O3 system (4–5 nm). The results from the nanoparticle size distributions were also found to be quite sensitive to the surrounding matrix, suggesting different mechanisms for the nanoparticle growth (particle migration and coalescence dominating in TiO2 and Ostwald ripening in Al2O3). These different clustering behaviours induced different transmittance-LSPR responses and a good mechanical stability, which opens the possibility for future use of these nanocomposite thin film systems in some envisaged applications (e.g. LSPR-biosensors).

Controlled aggregation of gold nanoparticles in a di-ureasilmatrix. Optical and micro indentation investigation

Nanocomposite materials with an organic-inorganic urea-silicate (di-ureasil) based matrix containing gold nanoparticles (NPs) were synthesized and characterized by optical (UV/Vis) spectroscopy and indentation measurement. The urea silicate gels were obtained by reaction between silicon alkoxyde modified by isocyanate group and polyethylene glycol oligomer with amine terminal groups in presence of catalyst. The latter ensures the successful incorporation of citrate-stabilized gold NPs in the matrix. It is shown that using a convenient destabilizing agent (AgNO3) and governing the preparative conditions, the aggregation degree of gold NPs can be controlled. The developed synthesis procedure significantly simplifies the preparative procedure of gold/urea silicate nanocomposites, compared to the procedure using gold NPs, preliminary covered with silica shells. Mechanical properties of the prepared sample were characterised using depth sensing indentation methods (DSI) and an idea about the type of aggregation structures was suggested.

Effect of acid or alkaline catalyst and of different capping agents on the optical properties of CdS nanoparticles incorporated within a diureasil hybrid matrix

CdS nanoparticles (NPs) were synthesized using colloidal methods and incorporated within a diureasil hybrid matrix. The surface capping of the CdS NPs by 3-mercaptopropyltrimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) organic ligands during the incorporation of the NPs within the hybrid matrix has been investigated. The matrix is based on poly(ethylene oxide)/poly(propylene oxide) chains grafted to a siliceous skeleton through urea bonds and was produced by sol–gel process. Both alkaline and acidic catalysis of the sol–gel reaction were used to evaluate the effect of each organic ligand on the optical properties of the CdS NPs. The hybrid materials were characterized by absorption, steady-state and time-resolved photoluminescence spectroscopy and High Resolution Transmission Electron Microscopy (HR-TEM). The preservation of the optical properties of the CdS NPs within the diureasil hybrids was dependent on the experimental conditions used. Both organic ligands (APTMS and MPTMS) demonstrated to be crucial in avoiding the increase of size distribution and clustering of the NPs within the hybrid matrix. The use of organic ligands was also shown to influence the level of interaction between the hybrid host and the CdS NPs. The CdS NPs showed large Stokes shifts and long average lifetimes, both in colloidal solution and in the xerogels, due to the origin of the PL emission in surface states. The CdS NPs capped with MPTMS have lower PL lifetimes compared to the other xerogel samples but still larger than the CdS NPs in the original colloidal solution. An increase in PL lifetimes of the NPs after their incorporation within the hybrid matrix is related to interaction between the NPs and the hybrid host matrix.

Biological behaviour of thin films consisting of Au nanoparticles dispersed in a TiO2 dielectric matrix

In this work it was studied the possible use of thin films, composed of Au nanoparticles (NPs) embedded in a TiO2 matrix, in biological applications, by evaluating their interaction with a well-known protein, Bovine Serum Albumin (BSA), as well as with microbial cells (Candida albicans). The films were produced by one-step reactive DC magnetron sputtering followed by heat-treatment. The samples revealed a composition of 8.3 at.% of Au and a stoichiometric TiO2 matrix. The annealing promoted grain size increase of the Au NPs from 3 nm (at 300 °C) to 7 nm (at 500 °C) and a progressive crystallization of the TiO2 matrix to anatase. A broad localized surface plasmon resonance (LSPR) absorption band (λ = 580–720 nm) was clearly observed in the sample annealed at 500 °C, being less intense at 300 °C. The biological tests indicated that the BSA adhesion is dependent on surface nanostructure morphology, which in turn depends on the annealing temperature that changed the roughness and wettability of the films. The Au:TiO2 thin films also induced a significant change of the microbial cell membrane integrity, and ultimately the cell viability, which in turn affected the adhesion on its surface. The microstructural changes (structure, grain size and surface morphology) of the Au:TiO2 films promoted by heat-treatment shaped the amount of BSA adhered and affected cell viability.

Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity

The relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging.

A systematic study of the structural and magnetic properties of Mn-, Co-, and Ni-Doped Colloidal Fe3O4 nanoparticles

A series of colloidal MxFe3-xO4 (M = Mn, Co, Ni; x = 0–1) nanoparticles with diameters ranging from 6.8 to 11.6 nm was synthesized by hydrothermal reaction in aqueous medium at low temperature (200 °C). Energy-dispersive X-ray microa-nalysis and inductively coupled plasma spectrometry confirms that the actual elemental compositions agree well with the nominal ones. The structural properties of obtained nanoparticles were investigated by using powder X-ray diffraction, Raman scattering, Mössbauer spectroscopy, and electron microscopy. The results demonstrate that our synthesis technique leads to the formation of chemically uniform single-phase solid solution nanoparticles with cubic spinel structure, confirming the intrinsic doping. Magnetic studies showed that, in comparison to Fe3O4, the saturation magnetization of MxFe3-xO4 (M = Mn, Ni) decreases with increasing dopant concentration, while Co-doped samples showed similar saturation magnetizations. On other hand, whereas Mn- and Ni-doped nanoparticles exhibits superparamagnetic behavior at room temperature, ferromagnetism emerges for CoxFe3-xO4 nanoparticles, which can be tuned by the level of Co doping.