Oxidative Precipitation Synthesis of Calcium-Doped Manganese Ferrite Nanoparticles for Magnetic Hyperthermia.

Superparamagnetic nanoparticles are of high interest for therapeutic applications. In this work, nanoparticles of calcium-doped manganese ferrites (CaxMn1-xFe2O4) functionalized with citrate were synthesized through thermally assisted oxidative precipitation in aqueous media. The method provided well dispersed aqueous suspensions of nanoparticles through a one-pot synthesis, in which the temperature and Ca/Mn ratio were found to influence the particles microstructure and morphology. Consequently, changes were obtained in the optical and magnetic properties that were studied through UV-Vis absorption and SQUID, respectively. XRD and Raman spectroscopy studies were carried out to assess the microstructural changes associated with stoichiometry of the particles, and the stability in physiological pH was studied through DLS. The nanoparticles displayed high values of magnetization and heating efficiency for several alternating magnetic field conditions, compatible with biological applications. Hereby, the employed method provides a promising strategy for the development of particles with adequate properties for magnetic hyperthermia applications, such as drug delivery and cancer therapy.

Magnetoliposomes Containing Multicore Nanoparticles and a New Antitumor Thienopyridine Compound with Potential Application in Chemo/Thermotherapy.

Multicore magnetic nanoparticles of manganese ferrite were prepared using carboxymethyl dextran as an agglutinating compound or by an innovative method using melamine as a cross-coupling agent. The nanoparticles prepared using melamine exhibited a flower-shape structure, a saturation magnetization of 6.16 emu/g and good capabilities for magnetic hyperthermia, with a specific absorption rate (SAR) of 0.14 W/g. Magnetoliposome-like structures containing the multicore nanoparticles were prepared, and their bilayer structure was confirmed by FRET (Förster Resonance Energy Transfer) assays. The nanosystems exhibited sizes in the range of 250-400 nm and a low polydispersity index. A new antitumor thienopyridine derivative, 7-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridine, active against HeLa (cervical carcinoma), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small-cell lung carcinoma) and HepG2 (hepatocellular carcinoma) cell lines, was loaded in these nanocarriers, obtaining a high encapsulation efficiency of 98 ± 2.6%. The results indicate that the new magnetoliposomes can be suitable for dual cancer therapy (combined magnetic hyperthermia and chemotherapy).

Development of Novel Magnetoliposomes Containing Nickel Ferrite Nanoparticles Covered with Gold for Applications in Thermotherapy.

Multifunctional nanosystems combining magnetic and plasmonic properties are a promising approach for cancer therapy, allowing magnetic guidance and a local temperature increase. This capability can provide a triggered drug release and synergistic cytotoxic effect in cancer cells. In this work, nickel ferrite/gold nanoparticles were developed, including nickel ferrite magnetic nanoparticles decorated with plasmonic gold nanoparticles and core/shell nanostructures (with a nickel ferrite core and a gold shell). These nanoparticles were covered with a surfactant/lipid bilayer, originating liposome-like structures with diameters below 160 nm. The heating capacity of these systems, upon excitation with light above 600 nm wavelength, was assessed through the emission quenching of rhodamine B located in the lipid layer. The developed nanosystems show promising results for future applications in thermotherapy.

Dehydropeptide-based plasmonic magnetogels: a supramolecular composite nanosystem for multimodal cancer therapy.

Supramolecular hydrogels are highly promising candidates as biomedical materials owing to their wide array of properties, which can be tailored and modulated. Additionally, their combination with plasmonic/magnetic nanoparticles to form plasmonic magnetogels further improves their potential in biomedical applications through the combination of complementary strategies, such as photothermia, magnetic hyperthermia, photodynamic therapy and magnetic-guided drug delivery. Here, a new dehydropeptide hydrogelator, Npx-l-Met-Z-ΔPhe-OH, was developed and combined with two different plasmonic/magnetic nanoparticle architectures, i.e., core/shell manganese ferrite/gold nanoparticles and gold-decorated manganese ferrite nanoparticles with ca. 55 nm and 45 nm sizes, respectively. The magnetogels were characterized via HR-TEM, FTIR spectroscopy, circular dichroism and rheological assays. The gels were tested as nanocarriers for a model antitumor drug, the natural compound curcumin. The incorporation of the drug in the magnetogel matrices was confirmed through fluorescence-based techniques (FRET, fluorescence anisotropy and quenching). The curcumin release profiles were studied with and without the excitation of the gold plasmon band. The transport of curcumin from the magnetogels towards biomembrane models (small unilamellar vesicles) was assessed via FRET between the fluorescent drug and the lipid probe Nile Red. The developed magnetogels showed promising results for photothermia and photo-triggered drug release. The magnetogels bearing gold-decorated nanoparticles showed the best photothermia properties, while the ones containing core/shell nanoparticles had the best photoinduced curcumin release.

Physicochemical characterisation and release behaviour of curcumin-loaded lactoferrin nanohydrogels into food simulants.

Whey protein nanostructures can be used as vehicles for the incorporation of nutraceuticals (e.g., antioxidants or vitamins) aimed at the development of functional foods, because nanostructures provide greater protection, stability and controlled release to such nutraceuticals. Fundamental knowledge is required regarding the behaviour of nanostructures when associated with nutraceuticals and their interactions with real food matrices. In this study, a lactoferrin (LF) nanohydrogel was developed to encapsulate curcumin (nutraceutical model) and its behaviour was evaluated in terms of the LF structure and the interaction with curcumin. The release kinetics of curcumin from LF nanohydrogels was also assessed using food simulants with a hydrophilic nature (10% ethanol) and lipophilic nature (50% ethanol). This system was able to encapsulate curcumin at 80 µg mL-1 with an efficiency of ca. 90% and loading capacity of ca. 3%. Through spectroscopic characterisation, it is suggested that LF and curcumin bind via hydrophobic interactions and the average binding distance between LF and curcumin was found to be 1.91 nm. Under refrigerated conditions (4 °C), this system showed stability for up to 35 days, while at room temperature (25 °C) it was shown to be stable for up to 14 days of storage. The LF nanohydrogel presented higher release rates of curcumin in a lipophilic food simulant (stable after ca. 7 h) as compared to a hydrophilic simulant (stable after ca. 4 h). LF nanohydrogels were successfully incorporated into a gelatine matrix and showed no degradation in this process. The behaviour of this system and the curcumin release kinetics in food stimulants make the LF nanohydrogel an interesting system to associate with lipophilic nutraceuticals and to incorporate in refrigerated food products of a hydrophilic nature.

Development of Multifunctional Liposomes Containing Magnetic/Plasmonic MnFe2O4/Au Core/Shell Nanoparticles.

Multifunctional liposomes containing manganese ferrite/gold core/shell nanoparticles were developed. These magnetic/plasmonic nanoparticles were covered by a lipid bilayer or entrapped in liposomes, which form solid or aqueous magnetoliposomes as nanocarriers for simultaneous chemotherapy and phototherapy. The core/shell nanoparticles were characterized by UV/Visible absorption, X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Superconducting Quantum Interference Device (SQUID). The magnetoliposomes were characterized by Dynamic Light Scattering (DLS) and TEM. Fluorescence-based techniques (FRET, steady-state emission, and anisotropy) investigated the incorporation of a potential anti-tumor drug (a thienopyridine derivative) in these nanosystems. The core/shell nanoparticles exhibit sizes of 25 ± 2 nm (from TEM), a plasmonic absorption band (λmax = 550 nm), and keep magnetic character. XRD measurements allowed for the estimation of 13.3 nm diameter for manganese ferrite core and 11.7 nm due to the gold shell. Aqueous magnetoliposomes, with hydrodynamic diameters of 152 ± 18 nm, interact with model membranes by fusion and are able to transport the anti-tumor compound in the lipid membrane, with a high encapsulation efficiency (EE (%) = 98.4 ± 0.8). Solid magnetoliposomes exhibit hydrodynamic diameters around 140 nm and also carry successfully the anticancer drug (with EE (%) = 91.2 ± 5.2), while also being promising as agents for phototherapy. The developed multifunctional liposomes can be promising as therapeutic agents for combined chemo/phototherapy.

Solid and aqueous magnetoliposomes as nanocarriers for a new potential drug active against breast cancer.

Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane. A promising application of these magnetoliposomes in oncology is anticipated, allowing a combined therapeutic approach, using both chemotherapy and magnetic hyperthermia.

Application of benzo[a]phenoxazinium chlorides in Antimicrobial Photodynamic Therapy of Candida albicans biofilms.

The use of Antimicrobial Photodynamic Therapy (APDT) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. The aim of this study was to verify the efficacy of photodynamic therapy using two new benzo[a]phenoxazinium photosensitizers against Candida albicans biofilms: N-(5-(3-hydroxypropylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSc) and N-(5-(11-hydroxyundecylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSd). The photodynamic activity of dyes against C. albicans biofilms was evaluated by incubating biofilms with dyes in the range of 100-300 µM for 3 or 18 h followed by illumination at 12 or 36 J cm(-2), using a xenon arc lamp (600 ± 2 nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300 µM of FSc with 18 h of incubation, followed by illumination at 36 J cm(-2). Contrarily, FSd had insignificant effect on biofilms inactivation by APDT. The higher uptake of FSc than FSd dye by biofilms during the dark incubation may explain the greater photodynamic effectiveness achieved with FSc. The results obtained stresses out the FSc-mediated APDT potential use to treat C. albicans infections.