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.

2,4,5-Triaminopyrimidines as blue fluorescent probes for cell viability monitoring: synthesis, photophysical properties, and microscopy applications.

Monitoring cell viability is critical in cell biology, pathology, and drug discovery. Most cell viability assays are cell-destructive, time-consuming, expensive, and/or hazardous. Herein, we present a series of newly synthesized 2,4,5-triaminopyrimidine derivatives able to discriminate between live and dead cells. To our knowledge, these compounds are the first fluorescent nucleobase analogues (FNAs) with cell viability monitoring potential. These new fluorescent molecules are synthesized using highly efficient and cost-effective methods and feature unprecedented photophysical properties (longer absorption and emission wavelengths, environment-sensitive emission, and unprecedented brightness within FNAs). Using a live-dead Saccharomyces cerevisiae cell and theoretical assays, the fluorescent 2,4,5-triaminopyrimidine derivatives were found to specifically accumulate inside dead cells by interacting with dsDNA grooves, thus paving the way for the emergence of novel and safe fluorescent cell viability markers emitting in the blue region. As the majority of commercially available viability dyes emit in the green to red region of the visible spectrum, these novel markers might be useful to meet the needs of blue markers for co-staining combinations.

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.

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.

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.

Plasmonic lipogels: driving co-assembly of composites with peptide-based gels for controlled drug release.

Supramolecular short peptide-based gels are promising materials for the controlled release of drugs (e.g. chemotherapeutic drugs) owing to the biocompatibility and similarity to cell matrix. However, the drug encapsulation and control over its release, mainly the hydrophilic drugs, can be a cumbersome task. This can be overcome through encapsulation/compartmentalization of drugs in liposomes, which can also enable spatiotemporal control and enhanced drug release through a trigger, such as photothermia. Having this in mind, we explored the assembly of silica-coated gold nanoparticles and liposomes (storage units) with dehydropeptide-based hydrogels as a proof-of-concept to afford peptide-based NIR light-responsive lipogels. Several liposomes compositions were assessed that displayed influence on the final assembly properties by combining with silica-coated gold nanorods (∼106 nm). Gold nanospheres (∼11 nm) were used to study the preparation method, which revealed the importance of initially combine liposomes with nanoparticles and then the gelator solution to achieve a closer proximity of the nanoparticles to the liposomes. The control over a hydrophilic model drug, 5(6)-carboxyfluorescein, was only achieved by its encapsulation in liposomes, in which the presence of silica-coated nanorods further enabled the use of photothermia to induce the liposomes phase transition and stimulate the drug release. Further, both composites, the liposomes and silica-coated gold nanorods, induced a lower elastic modulus, but also provided an enhanced gelation kinetics. Hereby, this work advances fabrication strategies for the development of short peptide-based hydrogels towards on-demand, sustained and controlled release of hydrophilic drugs through photothermia under NIR light irradiation.

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.

Chitosan Nano/Microformulations for Antimicrobial Protection of Leather with a Potential Impact in Tanning Industry.

Tanned leather can be attacked by microorganisms. To ensure resistance to bacteria on leather surfaces, protection solutions need to be developed, addressing both environmental issues and economic viability. In this work, chitosan nano/microparticles (CNP) and chitosan/silver nano/microstructures (CSNP), containing silver nanoparticles around 17 nm size, were incorporated into leather, obtained from the industrial process. Low loads of chitosan-based nano/microformulations, 0.1% mass ratio, resulted in total bacteria reduction (100%) after 2 h towards Gram-positive Staphylococcus aureus, both with CNP and CSNP coatings. Otherwise, comparable tests with the Gram-negative bacteria, Klebsiella pneumoniae, Escherichia coli, showed no significant improvement under the coating acidic conditions. The antimicrobial activity was evaluated by standard test methods: (1) inhibition halo and (2) dynamic contact conditions. The developed protection of leather either with CNP or CSNP is much higher than the one obtained with a simple chitosan solution.

Tuning the drug multimodal release through a co-assembly strategy based on magnetic gels.

Self-assembled short peptide-based gels are highly promising drug delivery systems. However, implementing a stimulus often requires screening different structures to obtain gels with suitable properties, and drugs might not be well encapsulated and/or cause undesirable effects on the gel's properties. To overcome this challenge, a new design approach is presented to modulate the release of doxorubicin as a model chemotherapeutic drug through the interplay of (di)phenylalanine-coated magnetic nanoparticles, PEGylated liposomes and doxorubicin co-assembly in dehydropeptide-based gels. The composites enable an enhancement of the gelation kinetics in a concentration-dependent manner, mainly through the use of PEGylated liposomes. The effect of the co-assembly of phenylalanine-coated nanoparticles with the hydrogel displays a concentration and size dependence. Finally, the integration of liposomes as doxorubicin storage units and of nanoparticles as composites that co-assemble with the gel matrix enables the tuneability of both passive and active doxorubicin release through a thermal, and a low-frequency alternating magnetic field-based trigger. In addition to the modulation of the gel properties, the functionalization with (di)phenylalanine improves the cytocompatibility of the nanoparticles. Hereby, this work paves a way for the development of peptide-based supramolecular systems for on-demand and controlled release of drugs.

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.

Carbon nanotube-reinforced cell-derived matrix-silk fibroin hierarchical scaffolds for bone tissue engineering applications.

In bone tissue engineering, the development of advanced biomimetic scaffolds has led to the quest for biomotifs in scaffold design that better recreate the bone matrix structure and composition and hierarchy at different length scales. In this study, an advanced hierarchical scaffold consisting of silk fibroin combined with a decellularized cell-derived extracellular matrix and reinforced with carbon nanotubes was developed. The goal of the carbon nanotube-reinforced cell-derived matrix-silk fibroin hierarchical scaffolds is to harvest the individual properties of their constituents to introduce hierarchical capacity in order to improve standard silk fibroin scaffolds. The scaffolds were fabricated using enzymatic cross-linking, freeze modeling, and decellularization methods. The developed scaffolds were assessed for the pore structure and mechanical properties showing satisfying results to be used in bone regeneration. The developed carbon nanotube-reinforced cell-derived matrix-silk fibroin hierarchical scaffolds were shown to be bioactive in vitro and expressed no hemolytic effect. Furthermore, cellular in vitro studies on human adipose-derived stem cells (hASCs) showed that scaffolds supported cell proliferation. The hASCs seeded onto these scaffolds evidenced similar metabolic activity to standard silk fibroin scaffolds but increased ALP activity. The histological staining showed cell infiltration into the scaffolds and visible collagen production. The expression of several osteogenic markers was investigated, further supporting the osteogenic potential of the developed carbon nanotube-reinforced cell-derived matrix-silk fibroin hierarchical scaffolds. The hemolytic assay demonstrated the hemocompatibility of the hierarchical scaffolds. Overall, the carbon nanotube-reinforced cell-derived matrix-silk fibroin hierarchical scaffolds presented the required architecture for bone tissue engineering applications.

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.

Supramolecular ultra-short carboxybenzyl-protected dehydropeptide-based hydrogels for drug delivery.

Self-assembled peptide-based hydrogels are promising materials for biomedical research owing to biocompatibility and similarity to the extracellular matrix, amenable synthesis and functionalization and structural tailoring of the rheological properties. Wider developments of self-assembled peptide-based hydrogels in biomedical research and clinical translation are hampered by limited commercial availability allied to prohibitive costs. In this work a focused library of Cbz-protected dehydrodipeptides Cbz-L-Xaa-Z-ΔPhe-OH (Xaa= Met, Phe, Tyr, Ala, Gly) was synthesised and evaluated as minimalist hydrogels. The Cbz-L-Met-Z-ΔPhe-OH and Cbz-L-Phe-Z-ΔPhe-OH hydrogelators were comprehensively evaluated regarding molecular aggregation and self-assembly, gelation, biocompatibility and as drug carriers for delivery of the natural compound curcumin and the clinically important antitumor drug doxorubicin. Drug release profiles and FRET studies of drug transport into small unilamellar vesicles (as biomembrane models) demonstrated that the Cbz-protected dehydropeptide hydrogels are effective nanocarriers for drug delivery. The expedite and scalable synthesis (in 3 steps), using commercially available reagents and amenable reaction conditions, makes Cbz-protected dehydrodipeptide hydrogels, widely available at affordable cost to the research community.

Impact of Citrate and Lipid-Functionalized Magnetic Nanoparticles in Dehydropeptide Supramolecular Magnetogels: Properties, Design and Drug Release.

Currently, the nanoparticle functionalization effect on supramolecular peptide-based hydrogels remains undescribed, but is expected to affect the hydrogels' self-assembly and final magnetic gel properties. Herein, two different functionalized nanoparticles: citrate-stabilized (14.4 ± 2.6 nm) and lipid-coated (8.9 ± 2.1 nm) magnetic nanoparticles, were used for the formation of dehydropeptide-based supramolecular magnetogels consisting of the ultra-short hydrogelator Cbz-L-Met-Z-ΔPhe-OH, with an assessment of their effect over gel properties. The lipid-coated nanoparticles were distributed along the hydrogel fibers, while citrate-stabilized nanoparticles were aggregated upon gelation, which resulted into a heating efficiency improvement and decrease, respectively. Further, the lipid-coated nanoparticles did not affect drug encapsulation and displayed improved drug release reproducibility compared to citrate-stabilized nanoparticles, despite the latter attaining a stronger AMF-trigger. This report points out that adsorption of nanoparticles to hydrogel fibers, which display domains that improve or do not affect drug encapsulation, can be explored as a means to optimize the development of supramolecular magnetogels to advance theranostic applications.

Magnetoliposomes Incorporated in Peptide-Based Hydrogels: Towards Development of Magnetolipogels.

A major problem with magnetogels is the encapsulation of hydrophobic drugs. Magnetoliposomes not only provide these domains but also improve drug stability and avert the aggregation of the magnetic nanoparticles. In this work, two magnetoliposome architectures, solid and aqueous, were combined with supramolecular peptide-based hydrogels, which are of biomedical interest owing to their biocompatibility, easy tunability, and wide array of applications. This proof-of-concept was carried out through combination of magnetoliposomes (loaded with the model drug curcumin and the lipid probe Nile Red) with the hydrogels prior to pH triggered gelation, and fluorescence spectroscopy was used to assess the dynamics of the encapsulated molecules. These systems allow for the encapsulation of a wider array of drugs. Further, the local environment of the encapsulated molecules after gelation is unaffected by the used magnetoliposome architecture. This system design is promising for future developments on drug delivery as it provides a means to independently modify the components and adapt and optimize the design according to the required conditions.

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.

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.