Elastic Liposomes Containing Calcium/Magnesium Ferrite Nanoparticles Coupled with Gold Nanorods for Application in Photothermal Therapy.

This work reports on the design, development, and characterization of novel magneto-plasmonic elastic liposomes (MPELs) of DPPC:SP80 (85:15) containing Mg0.75Ca0.25Fe2O4 nanoparticles coupled with gold nanorods, for topical application of photothermal therapy (PTT). Both magnetic and plasmonic components were characterized regarding their structural, morphological, magnetic and photothermal properties. The magnetic nanoparticles display a cubic shape and a size (major axis) of 37 ± 3 nm, while the longitudinal and transverse sizes of the nanorods are 46 ± 7 nm and 12 ± 1.6 nm, respectively. A new methodology was employed to couple the magnetic and plasmonic nanostructures, using cysteine as bridge. The potential for photothermia was evaluated for the magnetic nanoparticles, gold nanorods and the coupled magnetic/plasmonic nanoparticles, which demonstrated a maximum temperature variation of 28.9 °C, 33.6 °C and 37.2 °C, respectively, during a 30 min NIR-laser irradiation of 1 mg/mL dispersions. Using fluorescence anisotropy studies, a phase transition temperature (Tm) of 35 °C was estimated for MPELs, which ensures an enhanced fluidity crucial for effective crossing of the skin layers. The photothermal potential of this novel nanostructure corresponds to a specific absorption rate (SAR) of 616.9 W/g and a maximum temperature increase of 33.5 °C. These findings point to the development of thermoelastic nanocarriers with suitable features to act as photothermal hyperthermia agents.

Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release.

Nanotechnology has provided a new insight into cancer treatment by enabling the development of nanocarriers for the encapsulation, transport, and controlled release of antitumor drugs at the target site. Among these nanocarriers, magnetic nanosystems have gained prominence. This work presents the design, development, and characterization of magnetoliposomes (MLs), wherein superparamagnetic nanoparticles are coupled to the lipid surface. For this purpose, dimercaptosuccinic acid (DMSA)-functionalized Ca0.25Mg0.75Fe2O4 superparamagnetic nanoparticles were prepared for the first time. The magnetic nanoparticles demonstrated a cubic shape with an average size of 13.36 nm. Furthermore, their potential for photothermal hyperthermia was evaluated using 4 mg/mL, 2 mg/mL, and 1 mg/mL concentrations of NPs@DMSA, which demonstrated a maximum temperature variation of 20.4 °C, 11.4 °C, and 7.3 °C, respectively, during a 30 min NIR-laser irradiation. Subsequently, these nanoparticles were coupled to the lipid surface of DPPC/DSPC/CHEMS and DPPC/DSPC/CHEMS/DSPE-PEG-based MLs using a new synthesis methodology, exhibiting average sizes of 153 ± 8 nm and 136 ± 2 nm, respectively. Doxorubicin (DOX) was encapsulated with high efficiency, achieving 96% ± 2% encapsulation in non-PEGylated MLs and 98.0% ± 0.6% in stealth MLs. Finally, drug release assays of the DOX-loaded DPPC/DSPC/CHEMS MLs were performed under different conditions of temperature (37 °C and 42 °C) and pH (5.5 and 7.4), simulating physiological and therapeutic conditions. The results revealed a higher release rate at 42 °C and acidic pH. Release rates significantly increased when introducing the stimulus of laser-induced photothermal hyperthermia at 808 nm (1 W/cm2) for 5 min. After 48 h of testing, at pH 5.5, 67.5% ± 0.5% of DOX was released, while at pH 7.4, only a modest release of 27.0% ± 0.1% was achieved. The results demonstrate the potential of the MLs developed in this work to the controlled release of DOX under NIR-laser stimulation and acidic environments and to maintain a sustained and reduced release profile in physiological environments with pH 7.4.

Bovine Lactoferrin-Loaded Plasmonic Magnetoliposomes for Antifungal Therapeutic Applications.

Bovine lactoferrin (bLf) is a milk-derived protein that exhibits potent broad-spectrum antifungal activity against multiple fungi. bLf is susceptible to degradation, while some of its properties depend on the tertiary structure. So, the encapsulation of bLf in stimuli-responsive therapeutic formulations provides an added value to enhance its biological activities. Plasmonic magnetoliposomes (PMLs) arise as promising nanocarriers for dual hyperthermia (magneto-photothermia) and local chemotherapy, since the combination of magnetic and gold nanoparticles (NPs) in a single nanosystem (multifunctional liposomes) enables the targeting and controlled release of loaded drugs. In this work, plasmonic magnetoliposomes (PMLs) containing manganese ferrite nanoparticles (28 nm size) and gold nanoparticles (5-7.5 nm size), functionalized with 11-mercaptoundecanoic acid or octadecanethiol, were prepared and loaded with bLf. The NPs' optical, magnetic and structural properties were measured via UV/vis/NIR absorption spectroscopy, SQUID and TEM, respectively. The Specific Absorption Rate (SAR) was calculated to assess the capabilities for magnetic and photothermal hyperthermia. Finally, the antifungal potential of bLf-loaded PMLs and their mechanism of internalization were assessed in Saccharomyces cerevisiae by counting the colony forming units and using fluorescence microscopy. The results demonstrate that PMLs are mainly internalized through an energy- and temperature-dependent endocytic process, though the contribution of a diffusion component cannot be discarded. Most notably, only bLf-loaded plasmonic magnetoliposomes display cytotoxicity with an efficiency similar to free bLf, attesting their promising potential for bLf delivery in the context of antifungal therapeutic interventions.

Development of pH-Sensitive Magnetoliposomes Containing Shape Anisotropic Nanoparticles for Potential Application in Combined Cancer Therapy.

Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg0.75Ca0.25Fe2O4) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg0.75Ca0.25Fe2O4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.

Liposomal Formulations Loaded with a Eugenol Derivative for Application as Insecticides: Encapsulation Studies and In Silico Identification of Protein Targets.

A recently synthesized new eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate, with a high insecticidal activity against Sf9 (Spodoptera frugiperda) insect cells, was encapsulated in the liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and 100% dioleoylphosphatidylglycerol (DOPG), aiming at the future application as insecticides. Compound-loaded DOPG liposomes have sizes of 274 ± 12 nm, while Egg-PC:Ch liposomes exhibit smaller hydrodynamic diameters (69.5 ± 7 nm), high encapsulation efficiency (88.8 ± 2.7%), higher stability, and a more efficient compound release, thus, they were chosen for assays in Sf9 insect cells. The compound elicited a loss of cell viability up to 80% after 72 h of incubation. Relevantly, nanoencapsulation maintained the toxicity of the compound toward insect cells while lowering the toxicity toward human cells, thus showing the selectivity of the system. Structure-based inverted virtual screening was used to predict the most likely targets and molecular dynamics simulations and free energy calculations were used to demonstrate that this molecule can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase. The results are promising for the future application of compound-loaded nanoliposome formulations as crop insecticides.

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 Thermo- and pH-Sensitive Liposomal Magnetic Carriers for New Potential Antitumor Thienopyridine Derivatives.

The development of stimuli-sensitive drug delivery systems is a very attractive area of current research in cancer therapy. The deep knowledge on the microenvironment of tumors has supported the progress of nanosystems' ability for controlled and local fusion as well as drug release. Temperature and pH are two of the most promising triggers in the development of sensitive formulations to improve the efficacy of anticancer agents. Herein, magnetic liposomes with fusogenic sensitivity to pH and temperature were developed aiming at dual cancer therapy (by chemotherapy and magnetic hyperthermia). Magnetic nanoparticles of mixed calcium/manganese ferrite were synthesized by co-precipitation with citrate and by sol-gel method, and characterized by X-ray diffraction (XRD), scanning electron microscopy in transmission mode (STEM), and superconducting quantum interference device (SQUID). The citrate-stabilized nanoparticles showed a small-sized population (around 8 nm, determined by XRD) and suitable magnetic properties, with a low coercivity and high saturation magnetization (~54 emu/g). The nanoparticles were incorporated into liposomes of dipalmitoylphosphatidylcholine/cholesteryl hemisuccinate (DPPC:CHEMS) and of the same components with a PEGylated lipid (DPPC:CHEMS:DSPE-PEG), resulting in magnetoliposomes with sizes around 100 nm. Dynamic light scattering (DLS) and electrophoretic light scattering (ELS) measurements were performed to investigate the pH-sensitivity of the magnetoliposomes' fusogenic ability. Two new antitumor thienopyridine derivatives were efficiently encapsulated in the magnetic liposomes and the drug delivery capability of the loaded nanosystems was evaluated, under different pH and temperature conditions.

Amino Alcohols from Eugenol as Potential Semisynthetic Insecticides: Chemical, Biological, and Computational Insights.

A series of ß-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against Sf9 insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.

Magnetoliposomes Based on Magnetic/Plasmonic Nanoparticles Loaded with Tricyclic Lactones for Combined Cancer Therapy.

Liposome-like nanoarchitectures containing manganese ferrite nanoparticles covered or decorated with gold were developed for application in dual cancer therapy, combining chemotherapy and photothermia. The magnetic/plasmonic nanoparticles were characterized using XRD, UV/Visible absorption, HR-TEM, and SQUID, exhibiting superparamagnetic behavior at room temperature. The average size of the gold-decorated nanoparticles was 26.7 nm for MnFe2O4 with 5-7 nm gold nanospheres. The average size of the core/shell nanoparticles was 28.8 nm for the magnetic core and around 4 nm for the gold shell. Two new potential antitumor fluorescent drugs, tricyclic lactones derivatives of thienopyridine, were loaded in these nanosystems with very high encapsulation efficiencies (higher than 98%). Assays in human tumor cell lines demonstrate that the nanocarriers do not release the antitumor compounds in the absence of irradiation. Moreover, the nanosystems do not cause any effect on the growth of primary (non-tumor) cells (with or without irradiation). The drug-loaded systems containing the core/shell magnetic/plasmonic nanoparticles efficiently inhibit the growth of tumor cells when irradiated with red light, making them suitable for a triggered release promoted by irradiation.

Magnetoliposomes Based on Shape Anisotropic Calcium/Magnesium Ferrite Nanoparticles as Nanocarriers for Doxorubicin.

Multifunctional lipid nanocarriers are a promising therapeutic approach for controlled drug release in cancer therapy. Combining the widely used liposome structure with magnetic nanoparticles in magnetoliposomes allies, the advantages of using liposomes include the possibility to magnetically guide, selectively accumulate, and magnetically control the release of drugs on target. The effectiveness of these nanosystems is intrinsically related to the individual characteristics of the two main components-lipid formulation and magnetic nanoparticles-and their physicochemical combination. Herein, shape-anisotropic calcium-substituted magnesium ferrite nanoparticles (Ca0.25Mg0.75Fe2O4) were prepared for the first time, improving the magnetic properties of spherical counterparts. The nanoparticles revealed a superparamagnetic behavior, high saturation magnetization (50.07 emu/g at 300 K), and a large heating capacity. Furthermore, a new method for the synthesis of solid magnetoliposomes (SMLs) was developed to enhance their magnetic response. The manufacturing technicalities were optimized with different lipid compositions (DPPC, DPPC/Ch, and DPPC/DSPE-PEG) originating nanosystems with optimal sizes for biomedical applications (around or below 150 nm) and low polydispersity index. The high encapsulation efficiency of doxorubicin in these magnetoliposomes was proven, as well as the ability of the drug-loaded nanosystems to interact with cell membrane models and release DOX by fusion. SMLs revealed to reduce doxorubicin interaction with human serum albumin, contributing to a prolonged bioavailability of the drug upon systemic administration. Finally, the drug release kinetic assays revealed a preferable DOX release at hyperthermia temperatures (42 °C) and acidic conditions (pH = 5.5), indicating them as promising controlled release nanocarriers by either internal (pH) and external (alternate magnetic field) stimuli in cancer therapy.

Photodeposition of Silver on Zinc/Calcium Ferrite Nanoparticles: A Contribution to Efficient Effluent Remediation and Catalyst Reutilization.

The efficient photodegradation of textile dyes is still a challenge, especially considering resistant azo dyes. In this work, zinc/calcium mixed ferrite nanoparticles prepared by the sol-gel method were coupled with silver by a photodeposition method to enhance the photocatalytic potency. The obtained zinc/calcium ferrites are mainly cubic-shaped nanoparticles sized 15 ± 2 nm determined from TEM and XRD and an optical bandgap of 1.6 eV. Magnetic measurements indicate a superparamagnetic behavior with saturation magnetizations of 44.22 emu/g and 27.97 emu/g, respectively, for Zn/Ca ferrite and Zn/Ca ferrite with photodeposited silver. The zinc/calcium ferrite nanoparticles with photodeposited silver showed efficient photodegradation of the textile azo dyes C.I. Reactive Blue 250 and C.I. Reactive Yellow 145. Subsequent cycles of the use of the photocatalyst indicate the possibility of magnetic recovery and reutilization without a significant loss of efficiency.

New carvacrol and thymol derivatives as potential insecticides: synthesis, biological activity, computational studies and nanoencapsulation.

New compounds with potential insecticide activity were synthesized by structural modifications performed in the monoterpenoid phenolic moieties of carvacrol and thymol, resulting in a set of derivatives with the ether function containing the propyl, chloropropyl or hydroxypropyl chains, as well as a bicyclic ether with an unsaturated chain containing a carboxylic acid terminal. In addition, an analogue of carvacrol and thymol isomers bearing methoxyl, 1-hydroxyethyl and (3-chlorobenzoyl)oxy, instead of the three original methyl groups, was also synthesized. Several structural changes that resulted in diminished insecticide activity have been identified, but two significantly active molecules have been synthesized, one of them being less toxic to human cells than the naturally-derived starting materials. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these active molecules likely target the insect odorant binding proteins and/or acetylcholinesterase and are able to form stable complexes. For the most promising compounds, nanoencapsulation assays were carried out in liposomes of egg phosphatidylcholine/cholesterol (7 : 3) prepared by both thin film hydration and ethanolic injection methods. The compound-loaded liposomes were generally monodisperse and with sizes smaller than or around 200 nm. The thin film hydration method allowed high encapsulation efficiencies (above 85%) for both compounds and a delayed release, while for the systems prepared by ethanolic injection the encapsulation efficiency is lower than 50%, but the release is almost complete in two days.

Cytotoxic Plant Extracts towards Insect Cells: Bioactivity and Nanoencapsulation Studies for Application as Biopesticides.

The potential of plant extracts as bioinsecticides has been described as a promising field of agricultural development. In this work, the extracts of Punica granatum (pomegranate), Phytolacca americana (American pokeweed), Glandora prostrata (shrubby gromwell), Ulex europaeus (gorce), Tagetes patula (French marigold), Camellia japonica red (camellia), Ruta graveolens (rue or herb-of-grace) were obtained, purified, and their activity against Spodoptera frugiperda (Sf9) insect cells was investigated. From the pool of over twenty extracts obtained, comprising different polarities and vegetable materials, less polar samples were shown to be more toxic towards the insect cell line Sf9. Among these, a dichloromethane extract of R. graveolens was capable of causing a loss of viability of over 50%, exceeding the effect of the commercial insecticide chlorpyrifos. This extract elicited chromatin condensation and the fragmentation in treated cells. Nanoencapsulation assays of the cytotoxic plant extracts in soybean liposomes and chitosan nanostructures were carried out. The nanosystems exhibited sizes lower or around 200 nm, low polydispersity, and generally high encapsulation efficiencies. Release assays showed that chitosan nanoemulsions provide a fast and total extract release, while liposome-based systems are suitable for a more delayed release. These results represent a proof-of-concept for the future development of bioinsecticide nanoformulations based on the cytotoxic plant extracts.

Stealth Magnetoliposomes Based on Calcium-Substituted Magnesium Ferrite Nanoparticles for Curcumin Transport and Release.

Despite the promising pharmacological properties of curcumin, the transport and effective release of curcumin is still a challenge. The advances in functionalized nanocarriers for curcumin have also been motivated by the anticancer activity of this natural compound, aiming at targeted therapies. Here, stealth (aqueous and solid) magnetoliposomes containing calcium-substituted magnesium ferrite nanoparticles, CaxMg1-xFe2O4 (with x = 0.25, 0.50, 0.75) were developed as nanocarriers for curcumin. The magnetic nanoparticles exhibit superparamagnetic properties and crystalline structure, with sizes below 10 nm. The magnetoliposomes based on these nanoparticles have hydrodynamic diameters around or below 150 nm and a low polydispersity. The influence of an alternating magnetic field (AMF) on drug release over time was evaluated and compared with curcumin release by diffusion. The results suggest the potential of drug-loaded magnetoliposomes as nanocarriers that can be magnetically guided to the tumor sites and act as agents for a synergistic effect combining magnetic hyperthermia and controlled drug release.

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.

Magnetoliposomes Containing Calcium Ferrite Nanoparticles for Applications in Breast Cancer Therapy.

Magnetoliposomes containing calcium ferrite (CaFe2O4) nanoparticles were developed and characterized for the first time. CaFe2O4 nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new antitumor drugs. The magnetic nanoparticles were characterized by UV/Visible absorption, XRD, HR-TEM, and SQUID, exhibiting sizes of 5.2 ± 1.2 nm (from TEM) and a superparamagnetic behavior. The magnetoliposomes were characterized by DLS and TEM. The incorporation of two new potential antitumor drugs (thienopyridine derivatives) specifically active against breast cancer in these nanosystems was investigated by fluorescence emission and anisotropy. Aqueous magnetoliposomes, with hydrodynamic diameters around 130 nm, and solid magnetoliposomes with sizes of ca. 170 nm, interact with biomembranes by fusion and are able to transport the antitumor drugs with generally high encapsulation efficiencies (70%). These fully biocompatible drug-loaded magnetoliposomes can be promising as therapeutic agents in future applications of combined breast cancer therapy.

Novel dehydropeptide-based magnetogels containing manganese ferrite nanoparticles as antitumor drug nanocarriers.

Herein, novel dehydropeptide-based magnetogels, based on the hydrogelators Npx-l-Phe-Z-ΔAbu-OH, Npx-l-Trp-Z-ΔPhe-OH and Npx-l-Ala-Z-ΔPhe-Gly-l-Arg-Gly-l-Asp-Gly-OH and containing manganese ferrite nanoparticles (diameters around 20 nm), were prepared and characterized. TEM and FTIR measurements showed that the magnetogels maintained the fibrous structure of neat hydrogels, with fibres of ca. 20 nm average width (generally in the range 10-30 nm) and a few conformational changes relative to the neat hydrogels. The magnetogels were tested as nanocarriers for two potential fluorescent antitumor drugs: a thienopyridine derivative and the natural compound curcumin. FRET (Förster resonance energy transfer) from the aromatic moieties (energy donors) of gels to the fluorescent drugs (energy acceptors) and fluorescence anisotropy measurements confirmed the incorporation of both drugs into the magnetogel matrices. The transport of both drugs loaded into the magnetogels to membrane models (small unilamellar vesicles) was assessed by FRET between the fluorescent drugs and the dye Nile Red. The magnetogel possessing the RGD sequence was most promising for the delivery of the thienopyridine derivative, whereas three magnetogels were found to be suitable for the delivery of curcumin.

Microfluidic Deformability Study of an Innovative Blood Analogue Fluid Based on Giant Unilamellar Vesicles.

Blood analogues have long been a topic of interest in biofluid mechanics due to the safety and ethical issues involved in the collection and handling of blood samples. Although the current blood analogue fluids can adequately mimic the rheological properties of blood from a macroscopic point of view, at the microscopic level blood analogues need further development and improvement. In this work, an innovative blood analogue containing giant unilamellar vesicles (GUVs) was developed to mimic the flow behavior of red blood cells (RBCs). A natural lipid mixture, soybean lecithin, was used for the GUVs preparation, and three different lipid concentrations were tested (1 × 10-3 M, 2 × 10-3 M and 4 × 10-3 M). GUV solutions were prepared by thin film hydration with a buffer, followed by extrusion. It was found that GUVs present diameters between 5 and 7 µm which are close to the size of human RBCs. Experimental flow studies of three different GUV solutions were performed in a hyperbolic-shaped microchannel in order to measure the GUVs deformability when subjected to a homogeneous extensional flow. The result of the deformation index (DI) of the GUVs was about 0.5, which is in good agreement with the human RBC's DI. Hence, the GUVs developed in this study are a promising way to mimic the mechanical properties of the RBCs and to further develop particulate blood analogues with flow properties closer to those of real blood.

Magnetoliposomes containing magnesium ferrite nanoparticles as nanocarriers for the model drug curcumin.

Magnesium ferrite nanoparticles, with diameters around 25 nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behaviour, with a maximum magnetization of 16.2 emu g-1, a coercive field of 22.1 Oe and a blocking temperature of 183.2 K. These MgFe2O4 nanoparticles were used to produce aqueous and solid magnetoliposomes, with sizes below 130 nm. The potential drug curcumin was successfully incorporated in these nanosystems, with high encapsulation efficiencies (above 89%). Interaction by fusion between both types of drug-loaded magnetoliposomes (with or without PEGylation) and models of biological membranes was demonstrated, using FRET or fluorescence quenching assays. These results point to future applications of magnetoliposomes containing MgFe2O4 nanoparticles in cancer therapy, allowing combined magnetic hyperthermia and chemotherapy.

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.