Synthesis of alga-coated copper oxide nanoparticles with potential applications in shrimp farming.

Copper (Cu) is a crucial element that plays a vital role in facilitating proper biological activities in living organisms. In this study, copper oxide nanoparticles (CuO NPs) were synthesized using a straightforward precipitation chemical method from a copper nitrate precursor at a temperature of 85 °C. Subsequently, these NPs were coated with the aqueous extract of Sargassum angustifolium algae. The size, morphology, and coating of the NPs were analyzed through various methods, revealing dimensions of approximately 50 nm, a multidimensional shaped structure, and successful algae coating. The antibacterial activity of both coated and uncoated CuO NPs against Vibrio harveyi, a significant pathogen in Litopenaeus vannamei, was investigated. Results indicated that the minimum inhibitory concentration (MIC) for uncoated CuO NPs was 1000 µg/mL, whereas for coated CuO NPs, it was 500 µg/mL. Moreover, the antioxidant activity of the synthesized NPs was assessed. Interestingly, uncoated CuO NPs exhibited superior antioxidant activity (IC50 ≥ 16 µg/mL). The study also explored the cytotoxicity of different concentrations (10-100 µg/mL) of both coated and uncoated CuO NPs. Following 48 h of incubation, cell viability assays on shrimp hemocytes and human lymphocytes were conducted. The findings indicated that CuO NPs coated with alga extract at a concentration of 10 µg/mL increased shrimp hemocyte viability. In contrast, uncoated CuO NPs at a concentration of 25 µg/mL and higher, as well as CuO NPs at a concentration of 50 µg/mL and higher, led to a decrease in shrimp hemocyte survival. Notably, this study represents the first quantitative assessment of the toxicity of CuO NPs on shrimp cells, allowing for a comparative analysis with human cells.

Evaluating a targeted Palbociclib-Trastuzumab loaded smart niosome platform for treating HER2 positive breast cancer cells.

In this study, we present a targeted and pH-sensitive niosomal (pHSN) formulation, incorporating quantum dot (QD)-labeled Trastuzumab (Trz) molecules for the specific delivery of Palbociclib (Pal) to cells overexpressing human epidermal growth factor receptor 2 (HER2). FTIR analyses confirmed the successful preparation of the pHSNs and their bioconjugation. The labeled Trz-conjugated Pal-pHSNs (Trz-Pal-pHSNs) exhibited a size of approximately 170 nm, displaying a spherical shape with a neutral surface charge of -1.2 mV. Pal encapsulation reached ∼86%, and the release pattern followed a two-phase pH-dependent mechanism. MTT assessments demonstrated enhanced apoptosis induction, particularly in HER2-positive cells, by Trz-Pal-pHSNs. Fluorescence imaging further validated the internalization of particles into cells. In conclusion, Trz-Pal-pHSNs emerge as a promising platform for personalized medicine in the treatment of HER2-positive breast cancer.

Fabrication and characterization of 3D-printed composite scaffolds of coral-derived hydroxyapatite nanoparticles/polycaprolactone/gelatin carrying doxorubicin for bone tissue engineering.

In this study, nanocomposite scaffolds of hydroxyapatite (HA)/polycaprolactone (PCL)/gelatin (Gel) with varying amounts of HA (42-52 wt. %), PCL (42-52 wt. %), and Gel (6 wt. %) were 3D printed. Subsequently, a scaffold with optimal mechanical properties was utilized as a carrier for doxorubicin (DOX) in the treatment of bone cancer. For this purpose, HA nanoparticles were first synthesized by the hydrothermal conversion of Acropora coral and characterized by using different techniques. Also, a compression test was performed to investigate the mechanical properties of the fabricated scaffolds. The mineralization of the optimal scaffold was determined by immersing it in simulated body fluid (SBF) solution for 28 days, and the biocompatibility was investigated by seeding MG-63 osteoblast-like cells on it after 1-7 days. The obtained results showed that the average size of the synthesized HA particles was about 80 nm. The compressive modulus and strength of the scaffold with 47 wt. % HA was reported to be 0.29 GPa and 9.9 MPa, respectively, which was in the range of trabecular bones. In addition, the scaffold surface was entirely coated with an apatite layer after 28 days of soaking in SBF. Also, the efficiency and loading percentage of DOX were obtained as 30.8 and 1.6%, respectively. The drug release behavior was stable for 14 days. Cytotoxicity and adhesion evaluations showed that the fabricated scaffold had no negative effects on the viability of MG-63 cells and led to their proliferation during the investigated period. From these results, it can be concluded that the HA/PCL/Gel scaffold prepared in this study, in addition to its drug release capability, has good bioactivity, mechanical properties, and biocompatibility, and can be considered a suitable option for bone tumor treatment.

Thermo- and pH-responsive targeted lipid-coated mesoporous nano silica platform for dual delivery of paclitaxel and gemcitabine to overcome HER2-positive breast cancer.

In the current study, a new monoclonal antibody conjugated dual stimuli lipid-coated mesoporous silica nanoparticles (L-MSNs) platform was developed and investigated for specific co-delivery of the paclitaxel (PTX) and gemcitabine (Gem) to cancer cells and preventing their side effects during the treatment process. First, MSNs were synthesized and then coated with as-prepared pH-, and thermo-sensitive niosomes to produce L-MSNs. For this aim, Dipalmitoylphosphatidylcholine (DPPC) was used to create thermo-sensitivity, and 1, 2-Distearoyl-sn-glycerol-3-phosphoethanolamine -Citraconic Anhydride-Polyethylene Glycol (DSPE-CA-PEG) polymers were prepared and incorporated to the lipid layer for creation of pH-sensitivity. In the next step, trastuzumab as a monoclonal antibody (mAb) was conjugated to the maleimide groups of the 1, 2-Distearoyl-sn-glycerol-3-phosphoethanolamine DSPE-polyethylene glycol (PEG)-maleimide agents in the lipid bilayer via a disulfide bond. Dynamic light scattering (DLS) and zeta potential measurements, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM) analyses were utilized to characterize the synthesized particles before and after surface modification. The encapsulation efficiency (EE%) and loading efficiency (LE%) of the particles were also evaluated. Additionally, the drug release study and MTT assay were done to evaluate the bioactivity potential of the fabricated platforms. The results of DLS and zeta potential measurements revealed an average size of 200 nm and a neutral zeta potential of about -1 mV for mAb-L-MSNs. Also, the FTIR spectra confirmed the formation of mAb-L-MSNs. Moreover, SEM analysis showed spherical-shaped MSNs with amorphous structure confirmed by XRD analysis, and BET test revealed âˆ¼ 820 m2/g specific surface area and pore about 5 nm in size. The values of EE% and LE% of PTX were 90.3 % and 26.7 %, while these values for GEM were 89.5 % and 38.8 % in the co-loaded form, respectively. The thermo-pH-sensitivity examination showed approximately 500 nm of size increase after the change of pH and temperature from 7.4 and 37˚C to 5 and 42˚C. The release profile showed a pH-, and thermo-dependence manner, which led to about 89 % and 95 % of PTX and GEM released from the co-loaded platform at a pH of 5 and 42 °C while these values were 31.1 % and 32.2 % at pH of 7.4 and 37˚C, respectively. MTT assay data presented that when the mAb-L-co-loaded-MSNs platform containing 250 µg/mL drug was used, about 92 % of cells died in human epidermal receptors (HER2)-positive breast cancer cells (SKBR3), while just about 4 % of HER2-negative normal cells were killed. However, the growth inhibition rate of SKBR3 cells was caused by empty-mAb-L-MSNs, pure PTX and GEM combination were 9 % and 87 %, respectively. Moreover, the half inhibitory concentration (IC50) of the pure PTX, pure GEM, and mAb-coloaded-L-MSNs were 33, 17.6, and 6.5 µg/mL. The synergic effect of co-encapsulation of PTX and GEM in addition to trastuzumab conjugated L-MSNs was confirmed by a combinational index (CI) of 0.34. Therefore, this strategy leads to specific targeted drug delivery to cancer cells using a key-lock interaction between the trastuzumab and HER-2 receptors on the cancer cell membrane which stimuli the endocytosis of the particles to the cells followed by the destruction of the lipid layer in the acidic pH and the temperature of the lysosome, leading to enhanced release of PTX and GEM (pH of 5 and 42˚C). So, this platform can be considered a suitable carrier for cancer treatment.

PEG-Coated MnZn Ferrite Nanoparticles with Hierarchical Structure as MRI Contrast Agent.

In this work, MnZn ferrite nanoparticles with hierarchical morphology were synthesized hydrothermally, and their surface characteristics were improved by the PEGylation process. In vitro MRI studies were also conducted to evaluate the ability of the synthesized nanoparticles as a contrast agent. All results were compared with those obtained for MnZn ferrite nanoparticles with normal structure. Microstructural evaluations showed that in ferrite with hierarchical morphology, the spherical particles with an average size of ~20 nm made a distinctive structure consisting of rows of nanoparticles which is a relatively big assembly like a dandelion. The smaller particle size and dandelion-like morphology led to an increase in specific surface area for the hierarchical structure (~69 m2/g) in comparison to the normal one (~30 m2/g) with an average particle size of ~40 nm. In vitro MRI, cytotoxicity and hemocompatibility assays confirmed the PEG-coated MnZn ferrite nanoparticles with hierarchical structure synthesized in the current study can be considered as an MRI contrast agent.

Investigating the anti-streptococcal biofilm effect of ssDNA aptamer-silver nanoparticles complex on a titanium-based substrate.

Streptococcus mutans is a commensal and opportunistic pathogen that causes several diseases by forming a biofilm in humans and animals in many areas such as nasopharyngeal, cardiac valves, lungs, and oral cavity. Biofilms are very important in prosthetic infections associated with medical implants. The use of nanoparticles is one of the evolving fields in biofilm targeting. Silver nanoparticles can be used for biofilm targeting due to their inherent antimicrobial properties. Hybridization of nanoparticles with small molecules increases their biological properties and makes them multifunctional. The present investigation aimed to design an appropriate silver nanoparticles-aptamer complex that binds to the surface receptors of streptococcal strains. For this reason, silver nanoparticles with particle sizes in a range of 50 to 70 nm were synthesized and connected to a designed aptamer with a streptavidin-biotin linker. Then, the effect of the complex was investigated on the S. mutans biofilm formed on the surface of a medical-grade titanium substrate. The silver nanoparticles-aptamer complex at a concentration of 100 µg mL-1 after 48 h inhibited 43% of the biofilm formation and degraded 63% of the formed biofilm. Also, the cell availability reached 96% and the complex was stable in cell medium culture for 360 min. It was concluded that this complex could be a good candidate for removing the formed biofilms on the surface of titanium implants.

Fabrication of Chitosan-coated Mesoporous Silica Nanoparticles Bearing Rosuvastatin as a Drug Delivery System.

AIM: In this work, to improve the solubility and bioavailability of the rosuvastatin (RSV) drug, chitosan-coated mesoporous silica nanoparticles (CS-MSNs) as a drug delivery system were fabricated. METHODS: To do this, first MSNs with a maximum specific surface area were synthesized from sodium silicate as silica source and different molar ratios of cethyl trimethylammonium bromide (CTAB) and pluronics (P123, PEO20PPO17PEO20) as surfactants via the sol-gel process. Then, the synthesized MSNs were coated by CS polymer with the help of (3-glycidoxypropyl)methyldiethoxysilane (GPTMS) as a linker between MSNs and CS. Subsequently, the RSV drug was loaded into the synthesized CS-coated MSNs. The products were characterized by different techniques, including X-ray diffraction (XRD), the Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR). The in vitro drug release profile of the fabricated DDS was evaluated in a typical phosphate-buffered saline (PBS) solution at different pH values (i.e., 4, 6, and 7.4) for 48 h. To assess the cytotoxicity, the viability of the human fibroblast cells exposed to the fabricated DDS was also examined. RESULTS: The results showed that at an optimal molar ratio of P123/CTAB, the amorphous MSNs with a specific surface area of about 1080 m2/g, a pore diameter of 4 nm, a pore volume of 1.1 cm3/g, and an average size of about 30 nm were synthesized. Also, the presence of all the components, including the CS coating and the RSV drug, was confirmed in the structure of the fabricated DDS by FTIR analysis. Due to the pH-responsive feature of the CS coating, the RSV drug release from the fabricated DDS showed a reasonable environmental response; as the pH value of the PBS solution decreased, the degree of drug release increased. CONCLUSION: The CS coating enhanced the cytotoxicity of the fabricated DDS and led to sustainable drug release behavior, which would provide a beneficial approach for drug delivery technology.

Enhancement of astaxanthin production in Haematococcus pluvialis using zinc oxide nanoparticles.

Today, there is a great interest in using astaxanthin due to its potential health advantages. Application of different types of nanoparticles (NPs) as stress agents to enhance astaxanthin production in Haematococcus pluvialis, a microalgae strain, has been reported in the literature. In this study, the effect of different concentrations of zinc oxide (ZnO) NPs on the enhancement of astaxanthin production in H. pluvialis was investigated. First, ZnO NPs were synthesized from zinc nitrate as the precursor and sodium hydroxide (chemical method), and peel extract of pomegranate (green method) as reducing agents. To study the cell viability and stimulate the astaxanthin production, H. pluvialis cells were exposed to the different concentrations (i.e. 50, 100, 200, and 400 µg.ml-1) of ZnO NPs. The synthesized powders were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic light scattering (DLS) methods. The characterization results showed that the pure ZnO NPs were successfully synthesized via both methods with uniform particle size distribution. But, the average particle size of the green synthesized ZnO NPs (about 30 nm) was smaller than that of the chemically synthesized ones (about 80 nm). Maximum astaxanthin production (~ 20 mg.g-1 of dry biomass of H. pluvialis) was achieved at 100 µg.ml-1 of green synthesized ZnO NPs exposure to the H. pluvialis in comparison with the control culture after 15 days. However, ZnO NPs concentration above 200 µg.ml-1 was toxic to the microalgae. From these results, it can be concluded that a specific amount of ZnO NPs could be considered as a worthy candidate for the enhancement of astaxanthin production in H. pluvialis.

Fabrication and evaluation of a nerve guidance conduit capable of Ca2+ ion release to accelerate axon extension in peripheral nerve regeneration.

In this study, biodegradable nanocomposites consisting of poly (glycerol sebacate) (PGS) elastomeric matrix and the reinforcing phase of calcium titanate (CaTiO3 ) nanoparticles were fabricated as a nerve guidance conduit (NGC) for peripheral nerve regeneration. CaTiO3 nanoparticles were synthesized via the sol-gel method and calcined at 800°C for 60 min. PGS elastomer was synthesized via the polycondensation reaction of glycerol and sebacate (1:1) and 2.5 and 5 wt. percentages of the synthesized CaTiO3 nanoparticles were added to the PGS prepolymer solution. The composites obtained were heated in order to make crosslinks in the pre-polymer. CaTiO3 nanoparticles, PGS elastomer, and the composites fabricated were characterized in terms of their structural, chemical, physical, mechanical, and cell response properties to evaluate the feasibility of using the nanocomposite for NGC applications. The results indicated that CaTiO3 nanoparticles were 50 nm in size. When the nanoparticles were added to the PGS, the elastic modulus and tensile strength of the nanocomposite reached values of about 1 and 0.5 MPa, respectively that are near those of natural nerves. The degradation behavior and swelling of the nanocomposites, as compared with those of the PGS elastomer, were controlled by introducing CaTiO3 into the PGS, which swelling limitation could prevent nerve compression. It was observed that Ca2+ ions established chemical bonds with PGS, which led to high crosslink densities that, in turn, contribute to improved mechanical properties of the composite. The Ca2+ ions released from the nanocomposite samples were in the nontoxic range. The PC12 cell line on the surface of the nanocomposite specimens showed good cell adhesion and proliferation with improved axon outgrowth and extension. Based on the results obtained the fabricated PGS/CaTiO3 nanocomposite may be recommended as a suitable NGC with desirable effects on peripheral nerve regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2181-2189, 2018.