Magnetic and pH-responsive magnetite/chitosan (core/shell) nanoparticles for dual-targeted methotrexate delivery in cancer therapy.

Methotrexate successful therapy encounters various challenges in chemotherapy, such as poor oral bioavailability, low specificity, side effects and the development of drug resistances. In this study, it is proposed a dual-targeted nanocarrier comprising magnetite/chitosan nanoparticles for an efficient Methotrexate delivery. The formation of the particles was confirmed through morphological analysis using electron microscopy and elemental mappings via energy dispersive X-ray spectroscopy. These nanoparticles exhibited a size of ≈ 270 nm, a zeta potential of ≈ 24 mV, and magnetic responsiveness, as demonstrated by hysteresis cycle analysis and visual observations under a magnetic field. In addition, these particles displayed high stability, as evidenced by size and surface electric charge measurements, during storage at both 4 ºC and 25 ºC for at least 30 days. Electrophoretic properties were examined in relation to pH and ionic strength, confirming these core/shell nanostructure. The nanoparticles demonstrated a pH-responsive drug release as observed by a sustained Methotrexate release over the next 90 h under pH ≈ 7.4, while complete release occurred within 3 h under acidic conditions (pH ≈ 5.5). In the biocompatibility assessment, the magnetite/chitosan particles showed excellent hemocompatibility ex vivo and no cytotoxic effects on normal MCF-10 A and cancer MCF-7 cells. Furthermore, the Methotrexate-loaded nanoparticles significantly enhanced the antitumor activity reducing the half-maximal inhibitory concentration by ≈ 2.7-fold less compared to the free chemotherapeutic.

Development of surface-enhanced Raman scattering-sensing Method by combining novel Ag@Au core/shell nanoparticle-based SERS probe with hybridization chain reaction for high-sensitive detection of hepatitis C virus nucleic acid.

The ultrasensitive detection of hepatitis C virus (HCV) nucleic acid is crucial for the early diagnosis of hepatitis C. In this study, by combining Ag@Au core/shell nanoparticle (Ag@AuNP)-based surface-enhanced Raman scattering (SERS) tag with hybridization chain reaction (HCR), a novel SERS-sensing method was developed for the ultrasensitive detection of HCV nucleic acid. This SERS-sensing system comprised two different SERS tags, which were constructed by modifying Ag@AuNP with a Raman reporter molecule of 4-ethynylbezaldehyde, two different hairpin-structured HCR sequences (H1 or H2), and a detection plate prepared by immobilizing a capture DNA sequence onto the Ag@AuNP layer surface of the detection wells. When the target nucleic acid was present, the two SERS tags were captured on the surface of the Ag@AuNP-coated detection well to generate many "hot spots" through HCR, forming a strong SERS signal and realizing the ultrasensitive detection of the target HCV nucleic acid. The limit of detection of the SERS-sensing method for HCV nucleic acid was 0.47 fM, and the linear range was from 1 to 105 fM.

PEGylated mesoporous silica core-shell redox-responsive nanoparticles for delivering paclitaxel to breast cancer cells.

Controlling the drug release and restricting its presence in healthy organs is extremely valuable. In this study, mesoporous silica nanoparticles (MSN) as the core, loaded with paclitaxel (PTX), were coated with a non-porous silica shell functionalized with disulfide bonds. The nanoparticles were further coated with polyethylene glycol (PEG) via disulfide linkages. We analyzed the physicochemical properties of nanoparticles, including hydrodynamic size via Dynamic Light Scattering (DLS), zeta potential, X-ray Diffraction (XRD) patterns, Fourier-Transform Infrared (FTIR) spectra, and imaging through Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The drug release profile in two distinct glutathione (GSH) concentrations of 2 µM and 10 µM was measured. The cellular uptake of nanoparticles by MCF-7 cell line was determined using Confocal Laser Scanning Microscopy (CLSM) images and flow cytometry. Furthermore, the cell viability and the capability of nanoparticles to induce apoptosis in MCF-7 cell line were studied using the MTT assay and flow cytometry, respectively. Our investigations revealed that the release of PTX from the drug delivery system was redox-responsive. Also, results indicated an elevated level of cellular uptake and efficient induction of apoptosis, underscoring the promising potential of this redox-responsive drug delivery system for breast cancer therapy.

Synthesis of flaxseed gum/melanin-based scaffold: A novel approach for nano-encapsulation of doxorubicin with enhanced anticancer activity.

Doxorubicin is a powerful chemotherapy medicine that is frequently used to treat cancer, but because of its extremely destructive side effects on other healthy cells, its applications have been severely constrained. With the aim of using lower therapeutic doses of doxorubicin while maintaining the same anti-cancerous activity as those of higher doses, the present study designs nano-encapsulation of doxorubicin by acrylamide grafted melanin as core and acrylic acid grafted flax seed gum as shell (DOX@AAM-g-ML/AA-g-FSG-NPs) for studies in-vivo and in-vitro anticancer activity. For biological studies, the cytotoxicity of DOX@AAM-g-ML/AA-g-FSG-NPs was examined on a cancerous human cell line (HCT-15) and it was observed that DOX@AAM-g-ML/AA-g-FSG-NPs exhibited very high toxicity towards HCT-15. In-vivo investigation in colon cancer-inflicted rat model also showed that DOX@AAM-g-ML/AA-g-FSG-NPs showed better anticancer activity against cancerous cells as compared to free doxorubicin. The drug release behavior of DOX@GML-GFS-NPs was studied at several pH and maximum drug release (95 %) was recorded at pH -7.2, and kinetic data of drug release was follows the Higuchi (R2 = 0.9706) kinetic model. Our study is focussed on reducing the side effects of doxorubicin by its nano-encapsulation in acrylamide grafted melanin as core and acrylic acid grafted flax seed gum that will also enhance its efficiency.

Photothermal-Driven Polymer for a Smart Window with Adaptive Solar Modulation.

Although the thermochromic smart windows with adjustable sunlight transmittance to achieve energy savings are gradually improving, they are still difficult to use, limited by their unreasonable thermal response temperature, slow switching time, and poor durability. Here, we demonstrate a dual-function hybrid thermoresponsive smart window device (CPH) by trapping the phase-change polyHEA-HDA polymer (HEA = hydroxyethyl acrylate, HDA = hexadecyl acrylate) and polydopamine@CsxWO3 (PDA@CWO) core-shell nanoparticles within glasses. The introduced PDA@CWO nanoparticles substantially increase the energy transformation efficiency of solar energy to heat due to their outstanding photothermal conversion. When the temperature increases above the phase-transition temperature of polyHEA-HDA polymer, the copolymer components in the composite material undergo a reversible crystalline-amorphous transition, which enables the transformation of the whole smart window from transparency to opaque in a low ambient temperature. The light transmittance in the solar range can be dynamically modulated between 54.8 and 22.9% with a low ambient temperature while maintaining acceptable visible light transparency and effective UV shielding. A model house testing proves an indoor temperature cooling of 7.1 °C. This study offers a new approach to designing an energy-saving smart window system with multifunctionality.

Antimicrobial protection of two controlled release silver nanoparticles on simulated silk cultural relic.

HYPOTHESIS: Silver nanoparticles coated with organic-inorganic hybrid silica or inorganic silica have antimicrobial ability, and the coating can also effectively improve the dispersion and stability of the particles. The slow release of silver ions (Ag+) can improve the antimicrobial activity of silver nanoparticles. The synthesized nanoparticles are light yellow, which does not affect the look and feel of the silk cultural relics and meets the requirements of the principle of minimum interference. EXPERIMENTS: Two kinds of silver-based nanoparticles were synthesized: silver core-shell nanoparticle (Ag@mSiO2) and silver yolk-shell nanoparticle (Ag@YSiO2). The morphology, surface properties and Ag+ release efficiency of two nanoparticles were characterized. The antimicrobial effects of two nanoparticles on Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were compared. FINDINGS: Both of Ag@mSiO2 and Ag@YSiO2 had uniform size and good stability. Two nanoparticles had pore structure and silver nanocore, which provided the basis for the dissolution and exchange of Ag+. Because more silver ions were released, Ag@mSiO2 had higher antimicrobial activity than Ag@YSiO2 for A. niger and P. citrinum. For various silk samples, Ag@mSiO2 exhibited excellent antimicrobial properties. Meanwhile, there was little change in the color and tearing strength of Ag@mSiO2 coated silk.

Synthesis of acrylamide-g-melanin/itaconic acid-g-psyllium based nanocarrier for capecitabine delivery: In vivo and in vitro anticancer activity.

The present research aims to synthesize the capecitabine-loaded core-shell nanoparticles of acrylamide-grafted melanin and itaconic acid-grafted psyllium (Cap@AAM-g-ML/IA-g-Psy-NPs) to deliver the drug to the targeted colonic area, enhancing their anti-cancer activity. The drug release behavior of Cap@AAM-g-ML/IA-g-Psy-NPs was studied at several biological pH in which maximum drug release (95 %) was observed at pH 7.2. The drug release kinetic data was in accordance with the first-order (R2 = 0.9706) kinetic model. The cytotoxicity of Cap@AAM-g-ML/IA-g-Psy-NPs was investigated on HCT-15 cell line and Cap@AAM-g-ML/IA-g-Psy-NPs demonstrated outstanding toxicity towards HCT-15 cell line. In-vivo study on DMH-induced colon cancer rat model also exhibited that Cap@AAM-g-ML/IA-g-Psy-NPs enhanced anticancer activity against cancer cells as compared to capecitabine. Histology studies of heart, liver and kidney cells indicate that inflation due to cancer induction by DMH is significantly reduced when treated with Cap@AAM-g-ML/IA-g-Psy-NPs. Thus, the present study procures a worthwhile and nominal approach toward the synthesis of Cap@AAM-g-ML/IA-g-Psy-NPs for anticancer applications.

Electrochemical immunosensor for ultrasensitive detection of human papillomaviruse type 16 L1 protein based on Ag@AuNPs-GO/SPA.

Human papillomaviruse type 16 (HPV16) is a high-risk serotype. As the main protective antigen protein, L1 protein is also the target protein for diagnosis. A simple label free electrochemical immunosensor (ECIS) was fabricated for ultrasensitive detection of HPV16 L1 protein in this work. Quasi-spherical Ag@Au core-shell nanoparticles on graphene oxide (Ag@AuNPs-GO) was developed as current response amplifier and characterized by UV-Vis Spectroscopy, Transmission Electron Microscopy and energy dispersive X-ray spectroscopy. Staphylococcal protein A was decorated on the modified electrode and utilized to immobilized the Fc portion of the monoclonal antibody specific for HPV16 L1 protein. Cyclic Voltammetry, Differential Pulse Voltammetry and Electrochemical Impedance Spectroscopy were used to verify the electrochemical performance and interfacial kinetic property. The increased concentration of HPV16 L1 protein led to slow electron transport and linearly decreased differential pulse voltammetry peak current with a detection limit of 0.002 ng mL-1 and a wide linear relationship in the range of 0.005-400 ng mL-1at a regression coefficient (R2) of 0.9948. Furthermore, this ECIS demonstrated acceptable accuracy with good reproducibility, stability and selectivity, suggesting a promising immunological strategy for HPV typing and early screening.

Core-shell SERS nanotags-based western blot.

Western blot (WB) is the most commonly used scheme for protein identification in life science, but it still faces great challenges in the accurate quantitative detection of low-abundance proteins. Here, we proposed a novel surface-enhanced Raman scattering-based Western blot (SERS-WB) to solve this challenge. SERS nanotags were used as quantitative labels of proteins, which were composed of gold-silver core-shell nanoparticles, and Nile blue A (NBA) molecules were anchored on the interface of the core and shell. The results show that the SERS-WB possessed excellent sensitivity with detection limit of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein of 0.15 pg, as well as wide linear dynamic range (LDR) of 382 fg to 382 ng. In addition, the target protein on nitrocellulose (NC) membrane could be directly identified by colorimetric signal due to the aggregation effect of nanoparticles, which greatly simplifies the procedure. This as-proposed strategy will bring new thoughts to technological innovation of WB.

One-Step Synthesized Iron-Carbon Core-Shell Nanoparticles to Activate Persulfate for Effective Degradation of Tetrabromobisphenol A: Performance and Activation Mechanism.

Tetrabromobisphenol A (TBBPA), as an emerging endocrine disrupter, has been considered one of the persistent organic contaminants in water. It is urgently necessary to develop an efficient technique for the effective removal of TBBPA from water. Herein, a one-step hydrothermal synthesis route was employed to prepare a novel iron-carbon core-shell nanoparticle (Fe@MC) for effectively activating persulfate (PS) to degrade TBBPA. Morphological and structural characterization indicated that the prepared Fe@MC had a typical core-shell structure composed of a 5 nm thick graphene-like carbon shell and a multi-valence iron core. It can be seen that 94.9% of TBBPA (10 mg/L) could be degraded within 30 min at pH = 7. This excellent catalytic activity was attributed to the synergistic effect of the porous carbon shell and a multi-valence iron core. The porous carbon shell could effectively prevent the leaching of metal ions and facilitate PS activation due to its electron transfer capability. Furthermore, numerous micro-reaction zones could be formed on the surface of Fe@MC during the rapid TBBPA removal process. Radical quenching experiments and electron paramagnetic resonance (EPR) technology indicated that reactive oxygen species (ROS), including OH, SO4-, O2-, and 1O2, were involved in the TBBPA degradation process. Based on density functional theory (DFT) calculation, the carbon atoms linked by phenolic hydroxyl groups would be more vulnerable to attack by electron-rich groups; the central carbon was cracked and hydroxylated to generate short-chain aliphatic acids. The toxicity evaluation provides clear evidence for the promising application potential of our prepared material for the efficient removal of TBBPA from water.

Synergistic antibacterial activity of compact silver/magnetite core-shell nanoparticles core shell against Gram-negative foodborne pathogens.

The development of innovative antibacterial drugs against foodborne pathogens has led to an interest in novel materials such as nanomaterials. The unique features of nanomaterial qualify it for use as an antibacterial treatment. Noble metals and metal oxide nanoparticles, such as silver and magnetite nanoparticles, have been shown to be effective antibacterial medications against a range of microorganisms. In this work, Ag@Fe3O4 -NPs were fabricated by using a wet chemical reduction and modified co-precipitation techniques. The antibacterial efficiency of the Ag/Fe3O4 core shell nanoparticles was investigated by applying various techniques, such as the Kirby-Bauer Disk Diffusion test, minimum inhibitory concentration (MIC) and bactericidal concentration (MBC), Colony Forming Unit (CFU), and kill time assay. The toxicity mechanism of Ag@Fe3O4 -NPs against Salmonella typhimurium and Escherichia coli was studied by apoptosis and reactive oxygen species (ROS) assays. The data revealed that a cubic core was surrounded by a silver shell, which indicated the regular morphology of silver magnetite core shell nanoparticles without any aggregation. Furthermore, Ag@Fe3O4 -NPs is more toxic against S. typhimurium and E. coli than Ag-NPs and Fe3O4 NPs. The MIC values for Ag/Fe3O4 NPs against S. typhimurium and E. coli were 3.1 and 5.4 µg/ml, respectively, whereas the MIC values for Ag-NPs and MNPs against S. typhimurium and E. coli were 4.1 and 8.2 µg/ml for Ag-NPs and 6.9 and 10.3 µg/ml for MNPs. The results showed the ability of Ag@Fe3O4 -NPs to induce apoptosis by generating ROS. Also, the ability of Ag@Fe3O4 -NPs to liberate free Ag+ and generate ROS via the Haber-Weiss cycle may be a plausible mechanism to explain the toxicity of Ag@Fe3O4 -NPs - NPs.

The effect of near-surface electron trapping layer on the acetone sensing performance of black TiO2capped with ZnO.

In recent years, high-performance acetone gas sensors have attracted great attention for their potential in noninvasive blood glucose monitoring. In this work, black TiO2(B-TiO2) was introduced as an electron trapping layer between TiO2and ZnO to form TiO2@B-TiO2@ZnO core-shell nanoparticles, through a simple and safe method. The acetone sensing performance of TiO2@B-TiO2@ZnO varied with the thickness of ZnO. Because of the electron trapping effect of the introduced B-TiO2layer, the best performing sample exhibited a low optimal operating temperature of 275 °C and a high response of 49.25-50 ppm acetone. In addition, a low detection limit of 170 ppb was obtained. The pretty selectivity of the sample was also been proved. The mechanism of enhanced acetone response was explained by the energy band-based model of TiO2@B-TiO2@ZnO core-shell nanoparticle and depletion layer theory.

Sonodynamic Therapy Using Dacarbazine-Loaded AuSiO2 Nanoparticles for Melanoma Treatment: An In-Vitro Study on the B16F10 Murine Melanoma Cell Line.

The use of nanoparticles as a sonosensitizer in cancer sonodynamic therapy has been gaining attention because of their great advantages in drug delivery applications. By conjugating chemotherapy agents with nanoparticles, we can develop a drug delivery platform, control drug release and improve the outcome of treatments. The in-vitro study described here evaluates the combination of AuSiO2 nanoparticles and dacarbazine (DTIC@AuSiO2) as a sonosensitizer for sonodynamic therapy of melanoma. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays revealed that the viability of B16F10 melanoma cells was significantly inhibited by the increase in apoptosis induction in treatment with DTIC@AuSiO2 nanoparticles under ultrasound exposure compared with treatment with the free DTIC or AuSiO2 nanoparticles. The sonosensitization activity of AuSiO2 nanoparticles and greater uptake of DTIC by tumor cells after loading in DTIC@AuSiO2 nanoparticles inhibited the proliferation of melanoma tumor cells effectively. In conclusion, the DTIC@AuSiO2 nanoparticles established in this study could represent a good drug delivery and sonosensitizer platform for use in melanoma sonodynamic therapy.

Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Functionalized to EGF and Ce6 Complexes for Breast Cancer Diagnoses and Therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs) have some limitations in the physiological environment, however, a modification on their surface, such as a core-shell structure with gold (SPIONs@Au), can enhance their applicability. In this study, SPIONs were synthesized by the chemical coprecipitation method, stabilized by sodium citrate, and followed by the gold-coating process. SPIONs@Au were functionalized with EGF-α-lipoic acid and chlorin e6 (Ce6)-cysteamine complexes, composing a Theranostic Nanoprobe (TP). The outcomes showed that the SPIONs@Au had changed in color to red and had an absorption band centered at 530 nm. The coating was verified in the TEM micrographs in bright and dark fields by EDS mapping, which indicated the presence of Au and Fe. The Ce6-cysteamine complex had a resonant band at 670 nm that enabled the diagnosis of biological samples using fluorescence analysis. In the measure of TNBC cell uptake, the maximum value of TP fluorescence intensity was obtained within 4 h of internalization. At 2 h, the incorporation of the TP in the cytoplasm as well as in the nuclei was observed, suggesting that it could be employed as a diagnostic marker. The PTT results showed significant percentages of apoptosis in the TNBC cell line, which confirms the efficacy of the TP.

Optical biosensing of markers of mucosal inflammation.

We report the design and adaptation of iron/iron oxide nanoparticle-based optical nanobiosensors for enzymes or cytokine/chemokines that are established biomarkers of lung diseases. These biomarkers comprise ADAM33, granzyme B, MMP-8, neutrophil elastase, arginase, chemokine (C-C motif) ligand 20 and interleukin-6. The synthesis of nanobiosensors for these seven biomarkers, their calibration with commercially available enzymes and cytokines/chemokines, as well as their validation using bronchoalveolar lavage (BAL) obtained from a mouse model of TLR3-mediated inflammation are discussed here. Exhaled Breath Condensate (EBC) is a minimally invasive approach for sampling airway fluid in the diagnosis and management of various lung diseases in humans (e.g., asthma, COPD and viral infections). We report the proof-of-concept of using human EBC in conjunction with nanobiosensors for diagnosis/monitoring airway inflammation. These findings suggest that, with nanosensor technology, human EBC can be utilized as a liquid biopsy to monitor inflammation/remodeling in lung disease.

Polymeric nanocapsules: A review on design and production methods for pharmaceutical purpose.

Polymeric nanocapsules have extensive application potential in medical, biological, and pharmaceutical fields, and, therefore, much research has been dedicated to their production. Indeed, production protocols and the materials used are decisive for obtaining the desired nanocapsules characteristics and biological performance. In addition to that, several technological strategies have been developed in the last decade to improve processing techniques and form more valuable nanocapsules. This review provides a guide to current methods for developing polymeric nanocapsules, reporting aspects to be considered when choosing appropriate materials, and discussing different ways to produce nanocapsules for superior performances.

Brain-targeting delivery of MMB4 DMS using carrier-free nanomedicine CRT-MMB4@MDZ.

Brain-targeting delivery of 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) is limited by its hydrophilic property and chemical instability. In order to solve this problem, herein, we develop a facile protocol through combining antisolvent precipitation and emulsion-solvent evaporation method to synthesize midazolam (MDZ) coated MMB4 DMS (MMB4@MDZ) nanoparticles. The as-prepared MMB4@MDZ had a MMB4 DMS nanocrystal (MMB4-NC) core and a MDZ shell. The MDZ shell prevented the MMB4-NC core from contacting the aqueous environment, and thus, guaranteed the chemical stability of MMB4 DMS. Most charmingly, the iron mimic cyclic peptide CRTIGPSVC (CRT) was modified on MMB4@MDZ surfaces to produce CRT-MMB4@MDZ which was endowed with ability to absorb transferrin (Tf)-abundant corona. Taking advantages of the Tf-abundant corona, CRT-MMB4@MDZ achieved transferrin receptor (TfR)-mediated brain-targeting delivery. With the fascinating chemical stability and brain-targeting delivery effect, CRT-MMB4@MDZ showed great clinical transform prospect as a brand-new nanomedicine. Of particular importance, this work promised not only a core-shell carrier-free nanomedicine platform for effective delivery of unstable water-soluble drug, but also a protein corona-manipulating strategy for targeting delivery.

Hyaluronic Acid-Binding, Anionic, Nanoparticles Inhibit ECM Degradation and Restore Compressive Stiffness in Aggrecan-Depleted Articular Cartilage Explants.

Joint trauma results in the production of inflammatory cytokines that stimulate the secretion of catabolic enzymes, which degrade articular cartilage. Molecular fragments of the degraded articular cartilage further stimulate inflammatory cytokine production, with this process eventually resulting in post-traumatic osteoarthritis (PTOA). The loss of matrix component aggrecan occurs early in the progression of PTOA and results in the loss of compressive stiffness in articular cartilage. Aggrecan is highly sulfated, associates with hyaluronic acid (HA), and supports the compressive stiffness in cartilage. Presented here, we conjugated the HA-binding peptide GAHWQFNALTVRGSG (GAH) to anionic nanoparticles (hNPs). Nanoparticles conjugated with roughly 19 GAH peptides, termed 19 GAH-hNP, bound to HA in solution and increased the dynamic viscosity by 94.1% compared to an HA solution treated with unconjugated hNPs. Moreover, treating aggrecan-depleted (AD) cartilage explants with 0.10 mg of 19 GAH-hNP restored the cartilage compressive stiffness to healthy levels six days after a single nanoparticle treatment. Treatment of AD cartilage with 0.10 mg of 19 GAH-hNP inhibited the degradation of articular cartilage. Treated AD cartilage had 409% more collagen type II and 598% more GAG content than untreated-AD explants. The 19 GAH-hNP therapeutic slowed ECM degradation in AD cartilage explants, restored the compressive stiffness of damaged cartilage, and showed promise as a localized treatment for PTOA.

Improved Solvothermal Synthesis of γ-Fe2O3 Magnetic Nanoparticles for SiO2 Coating.

Monodisperse magnetic γ-Fe2O3 nanoparticles (MNPs) were prepared by a simple, improved, one-pot solvothermal synthesis using SDS and PEG 6000 as double capping reagents. This double protecting layer afforded better MNP uniformity (Z average 257 ± 11.12 nm, PDI = 0.18) and colloidal stability. Materials were characterized by DLS, SEM, TEM, XPS, and XRD. The use of these MNPs in the synthesis of core-shell structures with uniform and tunable silica coatings was demonstrated, as silica coated MNPs are important for use in a range of applications, including magnetic separation and catalysis and as platforms for templated nanogel synthesis.