Poly(levodopa)-Functionalized Polysaccharide Hydrogel Enriched in Fe3O4 Particles for Multiple-Purpose Biomedical Applications.

In recent years, there has been a significant increase in interest in the use of curdlan, a naturally derived polymer, for medical applications. However, it is relatively inactive, and additives increasing its biomedical potential are required; for example, antibacterial compounds, magnetic particles, or hemostatic agents. The stability of such complex constructs may be increased by additional functional networks, for instance, polycatecholamines. The article presents the production and characterization of functional hydrogels based on curdlan enriched with Fe3O4 nanoparticles (NPs) or Fe3O4-based heterostructures and poly(L-DOPA) (PLD). Some of the prepared modified hydrogels were nontoxic, relatively hemocompatible, and showed high antibacterial potential and the ability to convert energy with heat generation. Therefore, the proposed hydrogels may have potential applications in temperature-controlled regenerative processes as well as in oncology therapies as a matrix of increased functionality for multiple medical purposes. The presence of PLD in the curdlan hydrogel network reduced the release of the NPs but slightly increased the hydrogel's hemolytic properties. This should be taken into account during the selection of the final hydrogel application.

Temperature effects induced by NIR photo-stimulation within Ist and IInd optical biological windows of seed-mediated multi-shell nanoferrites.

Different types of ferrite core-shell structures, namely CoFe2O4@CoFe2O4, CoFe2O4@Fe3O4, CoFe2O4@MnFe2O4, and CoFe2O4@MnFe2O4@ZnFe2O4, were prepared by the seed-mediated approach. We show that this synthetic methodology offers great and important flexibility in the engineering of multi-shell ferrite nanoparticles which can be further used in various advanced applications. This impressive tool can be used for particle size tuning of homo- and heterostructures through convenient control of the concentration of metal acetylacetonates without the necessity of changing synthetic parameters, i.e., temperature, time, and solvent. The contactless conversion of laser light within Ist (808 nm) and IInd (1122 nm) biological optical windows was studied on the fabricated ferrite core-shell materials which showed promising heating effects that can be a basis of their practical exploitation in the biomedical field.

Synergic Temperature Effect of Star-like Monodisperse Iron Oxide Nanoparticles and Their Related Responses in Normal and Cancer Cells.

Magnetic nanoparticle (MNP) anisotropy has been tailored by the preparation of MNPs having different shapes (star-like, cubic, and polyhedral) using a self-modified rapid hot-injection process. The surface modification of MNPs was performed through etidronic ligand grafting with a strong binding affinity to mixed metal oxides, ensuring sufficient colloidal stability, surface protection, and minimized aggregation and interparticle interactions. The heating effect was induced by contactless external stimulation through the action of an alternating magnetic field and NIR laser radiation (808 nm). The efficacy of the energy conversion was evaluated as a function of the particle shape, concentration, and external stimuli parameters. In turn, the most efficient star-like particles have been selected to study their response in contact with normal and cancer cells. It was found that the star-like MNPs (Fe3O4 SL-NPs) at 2 mg/mL concentration induce necrosis and significantly alter cell cycle progression, while 0.5 mg/mL can stimulate the antioxidative and anti-inflammatory response in normal cells. A biologically relevant heating effect leading to heat-mediated cell death was achieved at a 2 mg/mL concentration of star-like particles and was enhanced by the addition of ascorbic acid (AA). AA-mediated photomagnetic hyperthermia can lead to the modulation of the heat-shock response in cancer cells that depends on the genotypic and phenotypic variations of cell lines.

Alternating magnetic field and NIR energy conversion on magneto-plasmonic Fe3O4@APTES-Ag heterostructures with SERS detection capability and antimicrobial activity.

Multipurpose Fe3O4@APTES-Ag heterostructures for mutual heat generation, SERS probing, and antimicrobial activity were fabricated using a three-step process. Silver metallic particles were precipitated on a thin silica shell that served as an interlayer with Fe3O4 nanocubes. The structural properties were studied by means of the powder X-ray diffraction technique, and selected area electron diffraction. Particle size, distribution, and morphology were evaluated using transmission electron microscopy, while element mapping was performed using the STEM-EDS technique. The presence of the silica shell and the effectiveness of the Ag reduction were checked by FTIR-ATR spectroscopy. The heat generation ability was studied by using AMF and NIR contactless external stimulations working separately and simultaneously. We demonstrated that the dual mode stimulation leads to a SAR (specific absorption rate) of 1000 W g-1 with the predominant role of the mechanism associated with the light interaction. The SERS effect was recorded with the use of the R6G standard molecule showing high capability of the heterostructures for Raman signal augmentation. Fe3O4 nanocubes decorated with Ag particles have shown antibacterial activity against P. aeruginosa. The Fe3O4@APTES-Ag presents promising potential as a multipurpose platform for biological applications ranging from photomagnetic therapies, to analytical probes exploiting the SERS effect and antibacterial activity.

Impact of Polyrhodanine Manganese Ferrite Binary Nanohybrids (PRHD@MnFe2O4) on Osteoblasts and Osteoclasts Activities-A Key Factor in Osteoporosis Treatment.

Osteoporosis is characterized by the reduction of bone mineral density and the weakness of the bone strength leading to fractures. Searching for new compounds that stimulate bone activity and their ability to reconstruct seems to be a promising tool in osteoporosis treatment. Here, we performed analyses comparing the impact of polyrhodanine (PRHD) and its derivatives on the viability (anti-proliferative tests), morphology and mitochondrial network (confocal microscopy) towards pre-osteoblasts (MC3T3-E1 cell line) and osteoclasts (4B12 cell line). Moreover, we assessed the expression of genes associated with the apoptosis, inflammation and osteogenic differentiation by qPCR technique. Our results clearly demonstrated that PRHD and its modification at ratio 10/90 significantly improves the pre-osteoblast's proliferative abilities, while reducing osteoclast function. The observed effects were strongly correlated with the cytoskeleton and mitochondrial network development and arrangement. Additionally, the expression profile of genes revealed enhanced apoptosis of osteoclasts in the case of PRHD and its modification at ratio 10/90. Moreover, in this case we also observed strong anti-inflammatory properties demonstrated by decreased expression of Il1b, Tnfa and Tgfb in pre-osteoblasts and osteoclasts. On the other hand, enhanced expression of the markers associated with bone remodeling, namely, osteopontin (OPN), osteocalcin (OCL) and alkaline phosphatase (ALP), seem to confirm the role of PRHD@MnFe2O4 in the promotion of differentiation of pre-osteoblasts through the ALP-OPN-OCL axis. Based on these observations, PRHD@MnFe2O4 could be a potential agent in osteoporosis treatment in future, however, further studies are still required.

Co0.5Mn0.5Fe2O4@PMMA Nanoparticles Promotes Preosteoblast Differentiation through Activation of OPN-BGLAP2-DMP1 Axis and Modulates Osteoclastogenesis under Magnetic Field Conditions.

The prevalence of osteoporosis in recent years is rapidly increasing. For this reason, there is an urgent need to develop bone substitutes and composites able to enhance the regeneration of damaged tissues which meet the patients' needs. In the case of osteoporosis, personalized, tailored materials should enhance the impaired healing process and restore the balance between osteoblast and osteoclast activity. In this study, we fabricated a novel hybrid material (Co0.5Mn0.5Fe2O4@PMMA) and investigated its properties and potential utility in the treatment of osteoporosis. The material structure was investigated with X-ray diffraction, Fourier-transform infrared spectroscopy with attenuated total reflectance, FTIR-ATR, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and selected area (electron) diffraction (SAED). Then, the biological properties of the material were investigated with pre-osteoblast (MC3T3-E1) and pre-osteoclasts (4B12) and in the presence or absence of magnetic field, using RT-qPCR and RT-PCR. During the studies, we established that the impact of the new hybrids on the pre-osteoblasts and pre-osteoclasts could be modified by the presence of the magnetic field, which could influence on the PMMA covered by magnetic nanoparticles impact on the expression of genes related to the apoptosis, cells differentiation, adhesion, microRNAs or regulating the inflammatory processes in both murine cell lines. In summary, the Co0.5Mn0.5Fe2O4@PMMA hybrid may represent a novel approach for material optimization and may be a way forward in the fabrication of scaffolds with enhanced bioactivity that benefits osteoporotic patients.

Multimodal polymer encapsulated CdSe/Fe3O4 nanoplatform with improved biocompatibility for two-photon and temperature stimulated bioapplications.

Multimodal polymer encapsulated CdSe/Fe3O4 nanoplatforms with dual optical and magnetic properties have been fabricated. We demonstrate that CdSe/Fe3O4 nanocapsules (NCs) upon excitation with UV radiation or NIR fs-laser excitation exhibit intense one- or two-photon emission at 535 nm, whereas the combination of an alternating magnetic field and 808 nm IR laser excitation results in heat generation. Since anticancer therapies require relatively high doses of Fe3O4 nanoparticles (NPs) to induce biologically relevant temperature jumps, the therapeutic effects of 0.1 and 1 mg/mL Fe3O4 NCs and CdSe/Fe3O4 NCs were investigated using breast cancer cell lines, ER-positive MCF-7, and triple-negative MDA-MB-231 cells. Improved biocompatibility of CdSe/Fe3O4 NCs compared to Fe3O4 NCs was revealed at higher NCs concentration suggesting safe potential medical applications of CdSe/Fe3O4 NCs. In contrast, 1 mg/mL Fe3O4 NCs were found to be more cytotoxic to MDA-MB-231 than MCF-7 cells through iron-induced oxidative stress, lipid peroxidation, and concomitant ferroptotic cell death. We believe that Fe3O4 NCs-mediated cellular response may be heterogeneous that reflects, at least in part, cancer cell genotype, molecular phenotype, and pathological classification.

Rapid hot-injection as a tool for control of magnetic nanoparticle size and morphology.

The rapid hot-injection (HI) technique was employed to synthesize magnetic nanoparticles with well-defined morphology (octahedrons, cubes, and star-like). It was shown that the proposed synthetic approach could be an alternative for the heat-up and flow hot-injection routes. Instant injection of the precursor to the hot reaction mixture (solvent(s) and additives) at high temperatures promotes fast nucleation and particle directional growth towards specific morphologies. We state that the use of saturated hydrocarbon namely hexadecane (sHD) as a new co-solvent affects the activity coefficient of monomers, forces shape-controllable growth, and allows downsizing of particles. We have shown that the rapid hot-injection route can be extended for other ferrites as well (ZnFe2O4, CoFe2O4, NiFe2O4, and MnFe2O4) which has not been done previously through the HI process before.

Efficient non-contact heat generation on flexible, ternary hydroxyapatite/curdlan/nanomagnetite hybrids for temperature controlled processes.

The ternary HAp/curdlan/nanomagnetite hybrids with ceramic and polymer phase incorporation of magnetite nanoparticles (MNPs) were fabricated to study their heating ability under action of the alternating magnetic field (AMF), 808 nm near infrared laser radiation (NIR) and their synergic stimulation. The energy conversion was evaluated in terms of the specific absorption rate (SAR) as a function of the MNPs concentration in composites and to estimate their potential in temperature-controlled regenerative processes and hyperthermia. Measurements were carried out on dry and Ringer's solution soaked composite materials in order to mimic in situ conditions. It was found that the MNPs release during prolonged experiment is limited and has no significant effect on energy conversion emphasizing stability of the hybrids. Incorporation of the MNPs in polymer phase of the hybrid can additionally limit particle leaking as well as plays a role as insulating layer for the heat dissipation lowering the risk of sample overheating. In general, it was shown that maximum temperature of hybrid can be achieved in a relatively short time of exposure to stimulating factors whereas its control can be done through optimization of experiment conditions. MNPs incorporation into the curdlan (polymer phase) lead to strengthening of the mechanical properties of the whole network.

Multifunctional Properties of Binary Polyrhodanine Manganese Ferrite Nanohybrids-From the Energy Converters to Biological Activity.

The PRHD@MnFe2O4 binary hybrids have shown a potential for applications in the biomedical field. The polymer cover/shell provides sufficient surface protection of magnetic nanoparticles against adverse effects on the biological systems, e.g., it protects against Fenton's reactions and the generation of highly toxic radicals. The heating ability of the PRHD@MnFe2O4 was measured as a laser optical density (LOD) dependence either for powders as well as nanohybrid dispersions. Dry hybrids exposed to the action of NIR radiation (808 nm) can effectively convert energy into heat that led to the enormous temperature increase ΔT 170 °C (>190 °C). High concentrated colloidal suspensions (5 mg/mL) can generate ΔT of 42 °C (65 °C). Further optimization of the nanohybrids amount and laser parameters provides the possibility of temperature control within a biologically relevant range. Biological interactions of PRHD@MnFe2O4 hybrids were tested using three specific cell lines: macrophages (RAW 264.7), osteosarcoma cells line (UMR-106), and stromal progenitor cells of adipose tissue (ASCs). It was shown that the cell response was strongly dependent on hybrid concentration. Antimicrobial activity of the proposed composites against Escherichia coli and Staphylococcus aureus was confirmed, showing potential in the exploitation of the fabricated materials in this field.

Yttrium-Doped Iron Oxide Nanoparticles for Magnetic Hyperthermia Applications.

Magnetic nanoparticles of Fe3O4 doped by different amounts of Y3+ (0, 0.1, 1, and 10%) ions were designed to obtain maximum heating efficiency in magnetic hyperthermia for cancer treatment. Single-phase formation was evident by X-ray diffraction measurements. An improved magnetization value was obtained for the Fe3O4 sample with 1% Y3+ doping. The specific absorption rate (SAR) and intrinsic loss of power (ILP) values for prepared colloids were obtained in water. The best results were estimated for Fe3O4 with 0.1% Y3+ ions (SAR = 194 W/g and ILP = 1.85 nHm2/kg for a magnetic field of 16 kA/m with the frequency of 413 kHz). The excellent biocompatibility with low cell cytotoxicity of Fe3O4:Y nanoparticles was observed. Immediately after magnetic hyperthermia treatment with Fe3O4:0.1%Y, a decrease in 4T1 cells' viability was observed (77% for 35 µg/mL and 68% for 100 µg/mL). These results suggest that nanoparticles of Fe3O4 doped by Y3+ ions are suitable for biomedical applications, especially for hyperthermia treatment.

Energy Conversion and Biocompatibility of Surface Functionalized Magnetite Nanoparticles with Phosphonic Moieties.

Magnetite nanoparticles (MNPs) were synthesized using two distinctly different approaches, co-precipitation (CP) and thermal decomposition (TD), and further surface functionalized with organophosphonic ligands containing different numbers of phosphonic groups. We have shown that it is possible to fabricate flower-like assemblies of MNPs through TD at lower temperatures, whereas CP MNPs formed agglomerates of particles with broad size distribution and irregular shapes. The effect of the organophosphonic ligands on the heating efficiency of the TD and CP MNPs under dual mode stimulation (simultaneous action of AMF and NIR laser radiation) was studied for the first time. It was found that in the case of the cost-effective CP MNP synthesis surface functionalization with chosen phosphonic ligands leads to higher heating efficiency upon laser stimulation, whereas better performance of TD MNPs was found under the action of AMF due to the significant difference of nanoparticle properties. The biocompatibility of surface functionalized MNPs with organophosphonic ligands was evaluated through thorough studies of the metabolic activity of MNPs in normal human foreskin fibroblasts as well as oxidative stress induction and oxidation stress response which has not been previously reported for most of the organophosphonic moieties used in this study.

Efficient NIR energy conversion of plasmonic silver nanostructures fabricated with the laser-assisted synthetic approach for endodontic applications.

Silver nanoparticles were synthesized with the laser-assisted wet chemical approach at room temperature. The effect of light exposure on the silver nanoparticles' spatial parameters shaping the localized surface plasmon resonance has been evaluated. The optical, structural and morphological characterizations of the Ag nanostructures were conducted with UV-VIS-NIR spectrophotometry, DLS and TEM techniques. The ability of the light-modified Ag nanostructures for energy conversion under the influence of 445 and 880 nm laser radiation is estimated. We have found that the most efficient heat generation can be achieved using triangular Ag nanostructures under the NIR irradiation (880 nm). The temperature effect on the Ag nanostructures' antibacterial properties has been evaluated against the Staphylococcus aureus population. The prospects of triangular Ag nanostructures' application on modern endodontics for the rapid nano-laser disinfection of the root canal system of the human tooth have been demonstrated.

Correction: Efficient NIR energy conversion of plasmonic silver nanostructures fabricated with the laser-assisted synthetic approach for endodontic applications.

[This corrects the article DOI: 10.1039/D0RA06614A.].

AMPK-mediated senolytic and senostatic activity of quercetin surface functionalized Fe3O4 nanoparticles during oxidant-induced senescence in human fibroblasts.

Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.

"False" cytotoxicity of ions-adsorbing hydroxyapatite - Corrected method of cytotoxicity evaluation for ceramics of high specific surface area.

An assessment of biomaterial cytotoxicity is a prerequisite for evaluation of its clinical potential. A material is considered toxic while the cell viability decreases under 70% of the control. However, extracts of certain materials are likely to reduce the cell viability due to the intense ions adsorption from culture medium (e.g. highly bioactive ceramics of high surface area). Thus, the standard ISO 10993-5 procedure is inappropriate for cytotoxicity evaluation of ceramics of high specific surface area because biomaterial extract obtained in this method (ions-depleted medium) is not optimal for cell cultures per se. Therefore, a simple test was designed as an alternative to ISO 10993-5 standard for cytotoxicity evaluation of the biomaterials of high surface area and high ions absorption capacity. The method, presented in this paper, included the evaluation of ceramics extract prepared according to corrected procedure. The corrected extract was found not cytotoxic (cell viability above 70%), suggesting that modified method for cytotoxicity evaluation of ions-adsorbing ceramics is more appropriate than ISO 10993-5 standard. For such biomaterials, the term "false" cytotoxicity is more suitable. Moreover, it was noted that NRU assay and microscopic observations should be recommended for cytotoxicity evaluation of ceramics of high surface area.

Lanthanum molybdate nanoparticles from the Bradley reaction: factors influencing their composition, structure, and functional characteristics as potential matrixes for luminescent phosphors.

Interaction of lanthanum isopropoxide with molybdenum(VI) alkoxides in La/Mo ratios varying from 3:1 to 1:1 in acetophenon or allyl alcohol as solvents offers nanosized poorly crystalline products of complex composition, where the precipitation of Mo-rich ones is followed by the formation of La-rich ones with conservation of the reaction stoichiometry in total. Thermal treatment of the precipitates at temperatures over 700 °C leads to the formation of stoichiometric phases of the α- and ß-La2Mo2O9 compositions. Introduction of smaller Re(3+) cations such as Sm(3+) by doping favors stabilization of the La2-xRExMo2O9 phase with improved crystallinity even after lower-temperature thermal treatment. The doping is successful only when the Re(3+) (Sm(3+), Eu(3+), and Tb(3+)) is introduced as an alkoxide: application of Re(3+)(acac)3 as Re(3+) sources leads to materials free from Re(3+). The produced samples were characterized by XPD, TGA, SEM, and TEM studies as well as the luminescent properties for the Sm(3+)-doped phases.

Visualization of custom-tailored iron oxide nanoparticles chemistry, uptake, and toxicity.

Nanoparticles of iron oxide generated by wearing of vehicles have been modelled with a tailored solution of size-uniform engineered magnetite particles produced by the Bradley reaction, a solvothermal metal-organic approach rendering hydrophilic particles. The latter does not bear any pronounced surface charge in analogy with that originating from anthropogenic sources in the environment. Physicochemical properties of the nanoparticles were thoroughly characterized by a wide range of methods, including XPD, TEM, SEM, DLS and spectroscopic techniques. The magnetite nanoparticles were found to be sensitive for transformation into maghemite under ambient conditions. This process was clearly revealed by Raman spectroscopy for high surface energy magnetite particles containing minor impurities of the hydromaghemite phase and was followed by quantitative measurements with EXAFS spectroscopy. In order to assess the toxicological effects of the produced nanoparticles in humans, with and without surface modification with ATP (a model of bio-corona formed in alveolar liquid), a pathway of potential uptake and clearance was modelled with a sequence of in vitro studies using A549 lung epithelial cells, lymphocyte 221-B cells, and 293T embryonal kidney cells, respectively. Raman microscopy unambiguously showed that magnetite nanoparticles are internalized within the A549 cells after 24 h co-incubation, and that the ATP ligand is retained on the nanoparticles throughout the uptake process. The toxicity of the nanoparticles was estimated using confocal fluorescence microscopy and indicated no principal difference for unmodified and modified particles, but revealed considerably different biochemical responses. The IL-8 cytokine response was found to be significantly lower for the magnetite nanoparticles compared to TiO(2), while an enhancement of ROS was observed, which was further increased for the ATP-modified nanoparticles, implicating involvement of the ATP signalling pathway in the epithelium.

Crystal structure and morphology evolution in the LaXO3, X = Al, Ga, In nano-oxide series. Consequences for the synthesis of luminescent phosphors.

The LaXO(3):Tb(3+) (X = Al(3+), Ga(3+), In(3+)) perovskite nanoparticles were obtained using the nonhydrolytic treatment (Bradley reaction) of the molecular precursors of the La(O(i)Pr)(3), Al(O(i)Pr)(3), Ga(O(i)Pr)(3), In(5)O(O(i)Pr)(13), and Tb(acac)(3), respectively. It was shown that crystal structure and morphology evolution in the LaXO(3), X = Al, Ga, In nano-oxide series depended on the size and chemical properties of the X-metal atom. Formation of the LaInO(3):Tb(3+) nanoparticles is distinctly less thermodynamically demanding on contrary to the LaAlO(3):Tb(3+) and LaGaO(3):Tb(3+) since it provided crystalline product directly in the solution synthesis at 202 °C, which is the lowest reported synthesis temperature for this compound up-to-date. This behavior was ascribed to the effects directly connected with the dopant substitution (exchange of bigger La(3+) cation with smaller Tb(3+)) as well as reduction of the particle size. The size effects are mostly reflected in the expansion of the cell volume, changes of the cell parameters as well as shifting and broadening of the Raman bands. Indirectly, size reduction has also an effect on the luminescence properties through the higher probability of presence of surface and net defects as well as heterogeneous distribution of the Tb(3+) ions caused by high surface-to-volume ratio. The prepared nanophosphors show basically green emission with exception of white-green in case of the LaInO(3):Tb(3+). Strong emission quenching was found in the latter case being most likely a consequence of the nonradiative energy transfer between Tb(3+) and In(3+) as well as the presence of defects. In comparison to the Pechini's method, the LaXO(3) nanoparticles required significantly lower annealing temperature (700 °C) necessary for complete crystallization. Generally the resulting particles are distinctly smaller (5 to 25 nm) and less agglomerated (50-100 nm) depending on the reaction conditions as well as thermal treatment. For the first time, it was shown that the LaGaO(3):Tb(3+) nanopowder has crystallized in the high-temperature rhombohedral R3c phase.