Chemical Strategies for Dendritic Magneto-plasmonic Nanostructures Applied to Surface-Enhanced Raman Spectroscopy.

Invited for the cover of this issue is the group of Tito Trindade and colleagues at the University of Aveiro. The image depicts dendritic magneto-plasmonic substrates for surface-enhanced Raman scattering (SERS) detection. Read the full text of the article at 10.1002/chem.202202382.

Chemical Strategies for Dendritic Magneto-plasmonic Nanostructures Applied to Surface-Enhanced Raman Spectroscopy.

Chemical analyses in the field using surface-enhanced Raman scattering (SERS) protocols are expected to be part of several analytical procedures applied to water quality monitoring. To date, these endeavors have been supported by developments in SERS substrate nanofabrication, instrumentation portability, and the internet of things. Here, we report distinct chemical strategies for preparing magneto-plasmonic (Fe3 O4 : Au) colloids, which are relevant in the context of trace-level detection of water contaminants due to their inherent multifunctionality. The main objective of this research is to investigate the role of poly(amidoamine) dendrimers (PAMAMs) in the preparation of SERS substrates integrating both functionalities into single nanostructures. Three chemical routes were investigated to design magneto-plasmonic nanostructures that translate into different ways for assessing SERS detection by using distinct interfaces. Hence, a series of magneto-plasmonic colloids have been characterized and then assessed for their SERS activity by using a model pesticide (thiram) dissolved in aqueous samples.

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.

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.

Magnetic Driven Nanocarriers for pH-Responsive Doxorubicin Release in Cancer Therapy.

Doxorubicin is one of the most widely used anti-cancer drugs, but side effects and selectivity problems create a demand for alternative drug delivery systems. Herein we describe a hybrid magnetic nanomaterial as a pH-dependent doxorubicin release carrier. This nanocarrier comprises magnetic iron oxide cores with a diameter of 10 nm, enveloped in a hybrid material made of siliceous shells and ĸ-carrageenan. The hybrid shells possess high drug loading capacity and a favorable drug release profile, while the iron oxide cores allows easy manipulation via an external magnetic field. The pH responsiveness was assessed in phosphate buffers at pH levels equivalent to those of blood (pH 7.4) and tumor microenvironment (pH 4.2 and 5). The nanoparticles have a loading capacity of up to 12.3 wt.% and a release profile of 80% in 5 h at acidic pH versus 25% at blood pH. In vitro drug delivery tests on human breast cancer and non-cancer cellular cultures have shown that, compared to the free drug, the loaded nanocarriers have comparable antiproliferative effect but a less intense cytotoxic effect, especially in the non-cancer cell line. The results show a clear potential for these new hybrid nanomaterials as alternative drug carriers for doxorubicin.

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.

Bio-Based Polyurethane Foams from Kraft Lignin with Improved Fire Resistance.

Rigid polyurethane foams (RPUFs) were synthesized using exclusively lignin-based polyol (LBP) obtained via the oxyalkylation of kraft lignin with propylene carbonate (PC). Using the design of experiments methodology combined with statistical analysis, the formulations were optimized to obtain a bio-based RPUF with low thermal conductivity and low apparent density to be used as a lightweight insulating material. The thermo-mechanical properties of the ensuing foams were compared with those of a commercial RPUF and a RPUF (RPUF-conv) produced using a conventional polyol. The bio-based RPUF obtained using the optimized formulation exhibited low thermal conductivity (0.0289 W/m·K), low density (33.2 kg/m3), and reasonable cell morphology. Although the bio-based RPUF has slightly lower thermo-oxidative stability and mechanical properties than RPUF-conv, it is still suitable for thermal insulation applications. In addition, the fire resistance of this bio-based foam has been improved, with its average heat release rate (HRR) reduced by 18.5% and its burn time extended by 25% compared to RPUF-conv. Overall, this bio-based RPUF has shown potential to replace petroleum-based RPUF as an insulating material. This is the first report regarding the use of 100% unpurified LBP obtained via the oxyalkylation of LignoBoost kraft lignin in the production of RPUFs.

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.

Potassium Ferrite for Biomedical Applications.

Ferrites have been widely studied for their use in the biomedical area, mostly due to their magnetic properties, which gives them the potential to be used in diagnostics, drug delivery, and in treatment with magnetic hyperthermia, for example. In this work, KFeO2 particles were synthesized with a proteic sol-gel method using powdered coconut water as a precursor; this method is based on the principles of green chemistry. To improve its properties, the base powder obtained was subjected to multiple heat treatments at temperatures between 350 and 1300 °C. The samples obtained underwent structural, morphological, biocompatibility, and magnetic characterization. The results show that upon raising the heat treatment temperature, not only is the wanted phase detected, but also the secondary phases. To overcome these secondary phases, several different heat treatments were carried out. Using scanning electron microscopy, grains in the micrometric range were observed. Saturation magnetizations between 15.5 and 24.1 emu/g were observed for the samples containing KFeO2 with an applied field of 50 kOe at 300 K. From cellular compatibility (cytotoxicity) assays, for concentrations up to 5 mg/mL, only the samples treated at 350 °C were cytotoxic. However, the samples containing KFeO2, while being biocompatible, had low specific absorption rates (1.55-5.76 W/g).

Chitosan/Alginate Nanogels Containing Multicore Magnetic Nanoparticles for Delivery of Doxorubicin.

In this study, multicore-like iron oxide (Fe3O4) and manganese ferrite (MnFe2O4) nanoparticles were synthesized and combined with nanogels based on chitosan and alginate to obtain a multimodal drug delivery system. The nanoparticles exhibited crystalline structures and displayed sizes of 20 ± 3 nm (Fe3O4) and 11 ± 2 nm (MnFe2O4). The Fe3O4 nanoparticles showed a higher saturation magnetization and heating efficiency compared with the MnFe2O4 nanoparticles. Functionalization with citrate and bovine serum albumin was found to improve the stability and modified surface properties. The nanoparticles were encapsulated in nanogels, and provided high drug encapsulation efficiencies (~70%) using doxorubicin as a model drug. The nanogels exhibited sustained drug release, with enhanced release under near-infrared (NIR) laser irradiation and acidic pH. The nanogels containing BSA-functionalized nanoparticles displayed improved sustained drug release at physiological pH, and the release kinetics followed a diffusion-controlled mechanism. These results demonstrate the potential of synthesized nanoparticles and nanogels for controlled drug delivery, offering opportunities for targeted and on-demand release in biomedical 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.

Assessing Cobalt Metal Nanoparticles Uptake by Cancer Cells Using Live Raman Spectroscopy.

PURPOSE: Nanotechnology applied to cancer treatment is a growing area of research in nanomedicine with magnetic nanoparticle-mediated anti-cancer drug delivery systems offering least possible side effects. To that end, both structural and chemical properties of commercial cobalt metal nanoparticles were studied using label-free confocal Raman spectroscopy. MATERIALS AND METHODS: Crystal structure and morphology of cobalt nanoparticles were studied by XRD and TEM. Magnetic properties were studied with SQUID and PPMS. Confocal Raman microscopy has high spatial resolution and compositional sensitivity. It, therefore, serves as a label-free tool to trace nanoparticles within cells and investigate the interaction between coating-free cobalt metal nanoparticles and cancer cells. The toxicity of cobalt nanoparticles against human cells was assessed by MTT assay. RESULTS: Superparamagnetic Co metal nanoparticle uptake by MCF7 and HCT116 cancer cells and DPSC mesenchymal stem cells was investigated by confocal Raman microscopy. The Raman nanoparticle signature also allowed accurate detection of the nanoparticle within the cell without labelling. A rapid uptake of the cobalt nanoparticles followed by rapid apoptosis was observed. Their low cytotoxicity, assessed by means of MTT assay against human embryonic kidney (HEK) cells, makes them promising candidates for the development of targeted therapies. Moreover, under a laser irradiation of 20mW with a wavelength of 532nm, it is possible to bring about local heating leading to combustion of the cobalt metal nanoparticles within cells, whereupon opening new routes for cancer phototherapy. CONCLUSION: Label-free confocal Raman spectroscopy enables accurately localizing the Co metal nanoparticles in cellular environments. The interaction between the surfactant-free cobalt metal nanoparticles and cancer cells was investigated. The facile endocytosis in cancer cells shows that these nanoparticles have potential in engendering their apoptosis. This preliminary study demonstrates the feasibility and relevance of cobalt nanomaterials for applications in nanomedicine such as phototherapy, hyperthermia or stem cell delivery.

Magnetic nanosorbents with siliceous hybrid shells of alginic acid and carrageenan for removal of ciprofloxacin.

Water contamination with antibiotics is a serious environmental threat. Ciprofloxacin (CIP) is one of the most frequently detected antibiotics in water. Herein, silica-based magnetic nanosorbents prepared using three seaweed polysaccharides, alginic acid, κ- and λ-carrageenan, were developed and evaluated in the uptake of ciprofloxacin. The sorbents were firstly characterized in detail to assess their morphology and composition. A systematic investigation was conducted to study the adsorption performance towards CIP, by varying the initial pH, contact time and initial CIP concentration. The maximum adsorption capacity was 464, 423 and 1350 mg/g for particles prepared from alginic acid, κ- and λ-carrageenan respectively. These high values indicate that these materials are among the most effective sorbents reported so far for the removal of CIP from water. The kinetic data were consistent with the pseudo-second-order model. The CIP adsorption on λ-carrageenan particles followed a cooperative process with sigmoidal isotherm that was described by the Dubinin-Radushkevich model. The high charge density of λ-carrageenan and the propensity of CIP molecules to self-aggregate may explain the cooperative nature of CIP adsorption. The sorbents were easily regenerated in mild conditions and could be reused in CIP removal up to 4 times without a significant loss of adsorptive properties.

Magnetic Nanoparticles of Zinc/Calcium Ferrite Decorated with Silver for Photodegradation of Dyes.

Magnetic nanoparticles of zinc/calcium ferrite and decorated with silver were prepared by coprecipitation method. The obtained nanoparticles were characterized by UV/Visible absorption, XRD, TEM and SQUID. The mixed zinc/calcium ferrites exhibit an optical band gap of 1.78 eV. HR-TEM imaging showed rectangular nanoplate shapes with sizes of 10 ± 3 nm and aspect ratio mainly between 1 and 1.5. Magnetic measurements indicated a superparamagnetic behavior. XRD diffractograms allowed a size estimation of 4 nm, which was associated with the nanoplate thickness. The silver-decorated zinc/calcium ferrite nanoparticles were successfully employed in the photodegradation of a model dye (Rhodamine B) and industrial textile dyes (CI Reactive Red 195, CI Reactive Blue 250 and CI Reactive Yellow 145). The nanosystems developed exhibited promising results for industrial application in effluent photoremediation using visible light, with the possibility of magnetic recovery.

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.