ResearchPad - Biomaterials https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer’s Disease-Related Pathology in APP/PS-1 Mice]]> https://www.researchpad.co/product?articleinfo=N69d6ab98-bd8d-4010-844a-59b94990e522

Introduction

Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aβ oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting.

Methods

Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice.

Results

In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer’s disease-related pathology.

Conclusion

Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.

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<![CDATA[Targeted Prodrug-Based Self-Assembled Nanoparticles for Cancer Therapy]]> https://www.researchpad.co/product?articleinfo=N2b0f5f7d-d5ab-49b6-9010-39c3b297e587

Background

Targeted prodrug has various applications as drug formulation for tumor therapy. Therefore, amphoteric small-molecule prodrug combined with nanoscale characteristics for the self-assembly of the nano-drug delivery system (DDS) is a highly interesting research topic.

Methods and Results

In this study, we developed a prodrug self-assembled nanoplatform, 2-glucosamine-fluorescein-5(6)-isothiocyanate-glutamic acid-paclitaxel (2DA-FITC-PTX NPs) by integration of targeted small molecule and nano-DDS with regular structure and perfect targeting ability. 2-glucosamine (DA) and paclitaxel were conjugated as the targeted ligand and anti-tumor chemotherapy drug by amino acid group. 2-DA molecular structure can enhance the targeting ability of prodrug-based 2DA-FITC-PTX NPs and prolong retention time, thereby reducing the toxicity of normal cell/tissue. The fluorescent dye FITC or near-infrared fluorescent dye ICG in prodrug-based DDS was attractive for in vivo optical imaging to study the behavior of 2DA-FITC-PTX NPs. In vitro and in vivo results proved that 2DA-FITC-PTX NPs exhibited excellent targeting ability, anticancer activity, and weak side effects.

Conclusion

This work demonstrates a new combination of nanomaterials for chemotherapy and may promote prodrug-based DDS clinical applications in the future.

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<![CDATA[Enzymatic Synthesis of Ricinoleyl Hydroxamic Acid Based on Commercial Castor Oil, Cytotoxicity Properties and Application as a New Anticancer Agent]]> https://www.researchpad.co/product?articleinfo=N2ee31eb3-084a-41f9-bd1c-0b276d684b2d

Background

New anticancer agents that rely on natural/healthy, not synthetic/toxic, components are very much needed.

Methods

Ricinoleyl hydroxamic acid (RHA) was synthesized from castor oil and hydroxylamine using Lipozyme TL IM as a catalyst. To optimize the conversion, the effects of the following parameters were investigated: type of organic solvent, period of reaction, amount of enzyme, the molar ratio of reactants and temperature. The highest conversion was obtained when the reaction was carried out under the following conditions: hexane as a solvent; reaction period of 48 hours; 120 mg of Lipozyme TL IM/3 mmol oil; HA-oil ratio of 19 mmol HA/3 mmol oil; and temperature of 40°C. The cytotoxicity of the synthesized RHA was assessed using human dermal fibroblasts (HDF), and its application towards fighting cancer was assessed using melanoma and glioblastoma cancer cells over a duration of 24 and 48 hours.

Results

RHA was successfully synthesized  and it demonstrated strong anticancer activity against glioblastoma and melanoma cells at as low as a 1 µg/mL concentration while it did not demonstrate any toxicity against HDF cells.

Conclusion

This is the first report on the synthesis of RHA with great potential to be used as a new anticancer agent.

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<![CDATA[Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy]]> https://www.researchpad.co/product?articleinfo=N0333ac7a-c329-4c80-b402-750b5176061b

Purpose

Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.

Methods

The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.

Results

The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.

Conclusion

Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.

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<![CDATA[Alginate-encapsulated brain-derived neurotrophic factor–overexpressing mesenchymal stem cells are a promising drug delivery system for protection of auditory neurons]]> https://www.researchpad.co/product?articleinfo=N0f470d8f-fd9f-4b6b-9074-0202356d0617

The cochlear implant outcome is possibly improved by brain-derived neurotrophic factor treatment protecting spiral ganglion neurons. Implantation of genetically modified mesenchymal stem cells may enable the required long-term brain-derived neurotrophic factor administration. Encapsulation of mesenchymal stem cells in ultra-high viscous alginate may protect the mesenchymal stem cells from the recipient’s immune system and prevent their uncontrolled migration. Alginate stability and survival of mesenchymal stem cells in alginate were evaluated. Brain-derived neurotrophic factor production was measured and its protective effect was analyzed in dissociated rat spiral ganglion neuron co-culture. Since the cochlear implant is an active electrode, alginate–mesenchymal stem cell samples were electrically stimulated and alginate stability and mesenchymal stem cell survival were investigated. Stability of ultra-high viscous-alginate and alginate–mesenchymal stem cells was proven. Brain-derived neurotrophic factor production was detectable and spiral ganglion neuron survival, bipolar morphology, and neurite outgrowth were increased. Moderate electrical stimulation did not affect the mesenchymal stem cell survival and their viability was good within the investigated time frame. Local drug delivery by ultra-high viscous-alginate-encapsulated brain-derived neurotrophic factor–overexpressing mesenchymal stem cells is a promising strategy to improve the cochlear implant outcome.

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<![CDATA[Synthesis and characterizations of o-nitrochitosan based biopolymer electrolyte for electrochemical devices]]> https://www.researchpad.co/product?articleinfo=5c706761d5eed0c4847c6f87

For the past decade, much attention was focused on polysaccharide natural resources for various purposes. Throughout the works, several efforts were reported to prepare new function of chitosan by chemical modifications for renewable energy, such as fuel cell application. This paper focuses on synthesis of the chitosan derivative, namely, O-nitrochitosan which was synthesized at various compositions of sodium hydroxide and reacted with nitric acid fume. Its potential as biopolymer electrolytes was studied. The substitution of nitro group was analyzed by using Attenuated Total Reflectance Fourier Transform Infra-Red (ATR-FTIR) analysis, Nuclear Magnetic Resonance (NMR) and Elemental Analysis (CHNS). The structure was characterized by X-ray Diffraction (XRD) and its thermal properties were examined by using differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). Whereas, the ionic conductivity of the samples was analyzed by electrochemical impedance spectroscopy (EIS). From the IR spectrum results, the nitro group peaks of O-nitrochitosan, positioned at 1646 and 1355 cm-1, were clearly seen for all pH media. At pH 6, O-nitrochitosan exhibited the highest degree of substitution at 0.74 when analyzed by CHNS analysis and NMR further proved that C-6 of glucosamine ring was shifted to the higher field. However, the thermal stability and glass transition temperatures were decreased with acidic condition. The highest ionic conductivity of O-nitrochitosan was obtained at ~10−6 cm-1. Overall, the electrochemical property of new O-nitrochitosan showed a good improvement as compared to chitosan and other chitosan derivatives. Hence, O-nitrochitosan is a promising biopolymer electrolyte and has the potential to be applied in electrochemical devices.

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<![CDATA[Optimization of Ralstonia solanacearum cell growth using a central composite rotational design for the P(3HB) production: Effect of agitation and aeration]]> https://www.researchpad.co/product?articleinfo=5c59fecdd5eed0c484135550

The intracellular accumulation of polyhydroxyalkanoates (PHAs) normally occurs after cell growth, during the second fermentation stage and under nutrient-limited conditions in the presence of a carbon excess. However, some microorganisms are able to accumulate PHAs as poly(3-hydroxybutyrate) [P(3HB)] during the first fermentation stage, the cell growth phase, without nutrient limitation, once they have been reported to utilize type II metabolism during the polymer accumulation phase. This study evaluated the effect of aeration and agitation on cell growth and P(3HB) accumulation in Ralstonia solanacearum RS, performed in a bioreactor for 24h at 32°C. A 22 central composite rotational design (CCRD) was used, with agitation (150 to 250 rpm) and aeration (0.3 to 1 vvm) as independent variables and optical density (OD600nm), dry cell weight (DCW), and P(3HB) yield as dependent variables. A significant polymer accumulation, until 70% of P(3HB), was observed, proving that R. solanacearum RS exhibited metabolism type II, regardless of the aeration process. The best results were obtained for 1 vvm and 250 rpm (+1, +1), with values of OD600nm (18.04) and DCW (4.82 g.L-1).

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<![CDATA[Antithrombotic properties of hemofilter coated with polymer having a hydrophilic blood-contacting layer]]> https://www.researchpad.co/product?articleinfo=5c79af65d5eed0c4841e2e2b

Objective:

Extracorporeal circulation devices are coated with a biocompatible polymer coating agent (BPCA) that has a hydrophilic blood-contacting layer, but hemofilters are not. We aimed to investigate the antithrombotic properties of a BPCA-coated hemofilter.

Methods:

Four experiments using BPCA-coated circuits and non-coated hemofilters and four experiments using BPCA-coated circuits and BPCA-coated hemofilters were performed with whole human blood and compared by measuring the circuit pressure every 5 min, antithrombin activity every 40 min, and thrombin–antithrombin complex every 40 min, for a total of 240 min of recirculation.

Results:

The mean time required for the pressure at the inlet of the hemofilter to increase sharply was longer in BPCA-coated than in non-coated hemofilters (66 ± 11 min vs 25 ± 9 min, p < 0.01). The mean antithrombin activity value at 200 and 240 min of recirculation was significantly higher in the experiments with BPCA-coated versus non-coated hemofilters (43.3 ± 2.87 vs 33.3 ± 5.74, p = 0.04; 42.8 ± 3.59 vs 31.0 ± 5.35, p = 0.01, respectively); the antithrombin activity values at the other time points were not significantly different. Furthermore, all thrombin–antithrombin complex values in experiments with the BPCA-coated hemofilters achieved overrange at 80 min of recirculation, whereas those with the non-coated hemofilter achieved overrange at 40 min.

Conclusion:

This study suggests that BPCA-coated hemofilters can inhibit antithrombin consumption, contributing to antithrombotic effects in extracorporeal circulation circuits.

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<![CDATA[Pulp-dentin regeneration: current approaches and challenges]]> https://www.researchpad.co/product?articleinfo=5c69eff8d5eed0c4841513f8

Regenerative endodontic procedures for immature permanent teeth with apical periodontitis confer biological advantages such as tooth homeostasis, enhanced immune defense system, and a functional pulp-dentin complex, in addition to clinical advantages such as the facilitation of root development. Currently, this procedure is recognized as a paradigm shift from restoration using materials to regenerate pulp-dentin tissues. Many studies have been conducted with regard to stem/progenitor cells, scaffolds, and biomolecules, associated with pulp tissue engineering. However, preclinical and clinical studies have evidently revealed several drawbacks in the current clinical approach to revascularization that may lead to unfavorable outcomes. Therefore, our review examines the challenges encountered under clinical conditions and summarizes current research findings in an attempt to provide direction for transition from basic research to clinical practice.

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<![CDATA[A study on stress distribution to cement layer and root dentin for post and cores made of CAD/CAM materials with different elasticity modulus in the absence of ferrule]]> https://www.researchpad.co/product?articleinfo=5c5f1b58d5eed0c48469b3f3

Background

To evaluate the stress distribution in a maxillary central incisor with different post and cores made of six CAD/CAM materials with different elastic modulus in the absence of ferrule using the finite element analysis.

Material and Methods

A three-dimensional endodontically treated maxillary central incisor restored with an all-ceramic crown was modelled in Rhinoceros (5.0 SR8, McNeel). The geometries were analyzed in ANSYS 17.2 (ANSYS Inc.) considering isotropic, homogeneous, linearly elastic materials with perfectly bonded contacts. The elastic moduli (E) of the post-and-cores defined the groups to be compared: nanoceramic resin (E=12.8GPa); composite resin (E=16GPa); hybrid ceramic (E=34.7GPa); lithium disilicate (E=95GPa); titanium (Ti-Al6-V4) (E=112GPa); and Y-TZP material (E=209.3GPa). The set was constrained in the cortical bone and loaded (45°/100 N) on the incisor palatine face. Stress distribution was analyzed by Maximum Principal Stress criteria for the crown-core cement line, Post-and-core’s cement line, Post-and-core system and Dentin.

Results

The stress distribution at the crown-core cement line (11.4 – 13.2 MPa) was inversely proportional to the increase of the elastic modulus of the post-core approaches, while it was direct proportional on the post-and-core (4.7 – 40 MPa) and cement line (4.1 – 6.2 MPa). Stress distribution on the dentin was similar for all groups (24.7 - 25.3).

Conclusions

Post-and-core made by CAD/CAM seems to be an efficient treatment alternative, since it is a conservative approach, promotes better aesthetic quality and it allows the control of the cement line thickness.

Key words:Endodontically treated teeth, Post-and-core technique, Ceramic crown, Finite element analysis, Biomimetics.

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<![CDATA[Engineering vasculature: Architectural effects on microcapillary-like structure self-assembly]]> https://www.researchpad.co/product?articleinfo=5c3e4faed5eed0c484d78005

One of the greatest obstacles to clinical translation of bone tissue engineering is the inability to effectively and efficiently vascularize scaffolds. The goal of this work was to explore systematically whether architecture, at a scale of hundreds of microns, can be used to direct the growth of microcapillary-like structures into the core of scaffolds. Biphasic bioceramic patterned architectures were produced using silicone molds of 3D printed parts. Grooves and ridges were designed to have widths of 330 μm and 660 μm, with periodicities respectively of 1240 μm and 630 μm. Groove depth was varied between 150 μm and 585 μm. Co-cultures of human dermal microvascular endothelial cells (HDMECs) and human osteoblasts (hOBs) were used to grow microcapillary-like structures on substrates. Bioceramic architecture was found to significantly affect microcapillary-like structure location and orientation. Microcapillary-like structures were found to form predominantly in grooves or between convexities. For all patterned samples, the CD31 (endothelial cell marker) signal was at least 2.5 times higher along grooves versus perpendicular to grooves. In addition, the average signal was at least two times higher within grooves than outside grooves for all samples. Grooves with a width of 330 μm and a depth of 300 μm resulted in the formation of individual, highly aligned microcapillary-like structures with lengths around 5 mm. Extensive literature has focused on the role of nano- and micro-topography (on the scale below tens of microns) on cellular response. However, the idea that architecture at a scale much larger than a cell could be used to modulate angiogenesis has not been systematically investigated. This work shows the crucial influence of architecture on microcapillary-like structure self-assembly at the scale of hundreds of microns. Elucidating the precise correspondence between architecture and microcapillary-like structure organization will ultimately allow the engineering of microvasculature by tuning local scaffold design to achieve desirable microvessel properties.

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<![CDATA[Zn-alloy provides a novel platform for mechanically stable bioresorbable vascular stents]]> https://www.researchpad.co/product?articleinfo=5c3667f5d5eed0c4841a6b17

Metallic Zn alloys have recently gained interest as potential candidates for developing platforms of bioresorbable vascular stents (BVS). Previous studies revealed that Mg alloys used for BVS can degrade too early, whereas PLLA materials may fail to provide effective scaffolding properties. Here we report on results of a new bioresorbable, metallic stent made from a Zn-Ag alloy studied in a porcine animal model of thrombosis and restenosis. While the tensile strength (MPa) of Zn-3Ag was higher than that of PLLA and resembled Mg’s (WE43), fracture elongation (%) of Zn-3Ag was much greater (18-fold) than the PLLA’s or Mg alloy’s (WE43). Zn-3Ag exposed to HAoSMC culture medium for 30 days revealed degradation elements consisting of Zn, O, N, C, P, and Na at a 6 nm surface depth. Platelet adhesion rates and blood biocompatibility did not differ between Zn-3Ag, PLLA, Mg (WE43), and non-resorbable Nitinol (NiTi) stent materials. Balloon-expandable Zn-3Ag alloy BVS implanted into iliofemoral arteries of 15 juvenile domestic pigs were easily visible fluoroscopically at implantation, and their bioresorption was readily detectable via X-ray over time. Histologically, arteries with Zn-3Ag BVS were completely endothelialized, covered with neointima, and were patent at 1, 3, and 6 months follow-up with no signs of stent thrombosis. Zn-3Ag alloy appears to be a promising material platform for the fabrication of a new generation of bioresorbable vascular stents.

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<![CDATA[Improved corrosion resistance of commercially pure magnesium after its modification by plasma electrolytic oxidation with organic additives]]> https://www.researchpad.co/product?articleinfo=5c217f15d5eed0c4844cc8c1

The optimal mechanical properties render magnesium widely used in industrial and biomedical applications. However, magnesium is highly reactive and unstable in aqueous solutions, which can be modulated to increase stability of reactive metals that include the use of alloys or by altering the surface with coatings. Plasma electrolytic oxidation is an efficient and tuneable method to apply a surface coating. By varying the plasma electrolytic oxidation parameters voltage, current density, time and (additives in the) electrolytic solution, the morphology, composition and surface energy of surface coatings are set. In the present study, we evaluated the influence on surface coatings of two solute additives, i.e. hexamethylenetetramine and mannitol, to base solutes silicate and potassium hydroxide. Results from in vitro studies in NaCl demonstrated an improvement in the corrosion resistance. In addition, coatings were obtained by a two-step anodization procedure, firstly anodizing in an electrolyte solution containing sodium fluoride and secondly in an electrolyte solution with hexamethylenetetramine and mannitol, respectively. Results showed that the first layer acts as a protective layer which improves the corrosion resistance in comparison with the samples with a single anodizing step. In conclusion, these coatings are promising candidates to be used in biomedical applications in particular because the components are non-toxic for the body and the rate of degradation of the surface coating is lower than that of pure magnesium.

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<![CDATA[Experimental investigations of the aerated polymethylmethacrylate-based vertebral cement flow in capillaries]]> https://www.researchpad.co/product?articleinfo=5c0f2288d5eed0c484f98ec4

Introduction:

A constant growth in the population suffering from osteoporotic vertebral weakening is observed. As a result, vertebroplasty procedures become more and more common. Unfortunately, they may be associated with several complications occurring during bone cement injection, including its leakage or overheating of tissues. Despite several experimental studies, there is a lack of data related to random aeration of the bone cement. Therefore, the main objective of the following investigations was to emphasize that random aeration of the bone cement, and, consequently, a compressibility factor, could not be treated as a negligible factor during the vertebroplasty procedure and had to be taken into account in the development of the mathematical model.

Materials and methods:

A special test rig to reproduce the vertebroplasty procedure was designed and built. The authors conducted numerous experiments on polymethylmethacrylate-based bone cement flows, analyzing different flow conditions, such as volume flow rate and flow channel diameter. Time periods of the flow front between characteristic sections and pressures (differential and gauge) were measured.

Results:

All investigations revealed that bone cements mixed in special mixing kits were characterized by a random level of aeration which led to varied flow parameters. Comparing the experimental results with the theoretical values of the continuity equation, the highest difference in the flow duration reached 140%.

Discussion:

It has been proven that the aeration of the bone cement alters the flow dynamics. Therefore, much more data are required for statistical analysis to validate a mathematical model of the bone cement flow.

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<![CDATA[Development and characterization of a nanoemulsion containing propranolol for topical delivery]]> https://www.researchpad.co/product?articleinfo=5b59c7b6463d7e7b3acb09b8

Background

Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo.

Methods

The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m.

Results

NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of −20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay.

Conclusion

We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas.

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<![CDATA[Biological responses to core&ndash;shell-structured Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub>-NH<sub>2</sub> nanoparticles in rats by a nuclear magnetic resonance-based metabonomic strategy]]> https://www.researchpad.co/product?articleinfo=5b5918bb463d7e552e096283

Background

Core–shell-structured nanoparticles (NPs) have attracted much scientific attention due to their promising potential in biomedical fields in recent years. However, their underlying mechanisms of action and potential adverse effects following administration remain unknown.

Methods

In the present study, a 1H nuclear magnetic resonance-based metabonomic strategy was applied to investigate the metabolic consequences in rats following the intravenous administration of parent NPs of core–shell-structured nanoparticles, Fe3O4@SiO2-NH2 (Fe@Si) NPs.

Results

Alterations reflected in plasma and urinary metabonomes indicated that Fe@Si NPs induced metabolic perturbation in choline, ketone-body, and amino-acid metabolism besides the common metabolic disorders in tricarboxylic acid cycle, lipids, and glycogen metabolism often induced by the exogenous agents. Additionally, intestinal flora metabolism and the urea cycle were also influenced by Fe@Si NP exposure. Time-dependent biological effects revealed obvious metabolic regression, dose-dependent biological effects implied different biochemical mechanisms between low- and high-dose Fe@Si NPs, and size-dependent biological effects provided potential windows for size optimization.

Conclusion

Nuclear magnetic resonance-based metabonomic analysis helps in understanding the biological mechanisms of Fe@Si NPs, provides an identifiable ground for the selection of view windows, and further serves the clinical translation of Fe@Si NP-derived and -modified bioprobes or bioagents.

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<![CDATA[Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium nanoparticles with amantadine through ROS-mediated AKT signaling pathways]]> https://www.researchpad.co/product?articleinfo=5b588ef9463d7e4bbcb756db

Introduction

As a therapeutic antiviral agent, the clinical application of amantadine (AM) is limited by the emergence of drug-resistant viruses. To overcome the drug-resistant viruses and meet the growing demand of clinical diagnosis, the use of biological nanoparticles (NPs) has increased in order to develop novel anti-influenza drugs. The antiviral activity of selenium NPs with low toxicity and excellent activities has attracted increasing attention for biomedical intervention in recent years.

Methods and results

In the present study, surface decoration of selenium NPs by AM (Se@AM) was designed to reverse drug resistance caused by influenza virus infection. Se@ AM with less toxicity remarkably inhibited the ability of H1N1 influenza to infect host cells through suppression of the neuraminidase activity. Moreover, Se@AM could prevent H1N1 from infecting Madin Darby Canine Kidney cell line and causing cell apoptosis supported by DNA fragmentation and chromatin condensation. Furthermore, Se@AM obviously inhibited the generation of reactive oxygen species and activation of phosphorylation of AKT.

Conclusion

These results demonstrate that Se@AM is a potentially efficient antiviral pharmaceutical agent for H1N1 influenza virus.

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<![CDATA[Ultrasound molecular imaging of breast cancer in MCF-7 orthotopic mice using gold nanoshelled poly(lactic-co-glycolic acid) nanocapsules: a novel dual-targeted ultrasound contrast agent]]> https://www.researchpad.co/product?articleinfo=5bfb9185d5eed0c484af9853

Background

The development of nanoscale molecularly targeted ultrasound contrast agents (UCAs) with high affinity and specificity is critical for ultrasound molecular imaging in the early detection of breast cancer.

Purpose

To prospectively evaluate ultrasound molecular imaging with dual-targeted gold nanoshelled poly(lactide-co-glycolic acid) nanocapsules carrying vascular endothelial growth factor receptor type 2 (VEGFR2) and p53 antibodies (DNCs) in MCF-7 orthotopic mice model.

Methods

DNCs were fabricated with an inner PLGA and outer gold nanoshell spherical structure. Its targeting capabilities were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) in vitro. Contrast-enhanced ultrasound imaging (CEUS) with DNCs was evaluated qualitatively and quantitatively in vitro and in MCF-7 orthotopic mice model by two different systems. The biodistribution of NCs in mice was preliminary investigated. Differences were calculated by using analysis of variance.

Results

DNCs showed a well-defined spherical morphology with an average diameter of 276.90±110.50 nm. In vitro, DNCs exhibited high target specificities (79.01±5.63% vs. 2.11±1.07%, P<0.01; 75.54±6.58% vs. 5.21±3.12%, P<0.01) in VEGFR2- and p53-positive cells compared with control cells. In vivo, CEUS displayed a significantly higher video intensity in two systems using DNCs in comparison with non-targeted PLGA@Au NCs and single-targeted NCs. Biodistribution studies revealed that more DNCs in breast cancer tissue could be detected in mice than in other NCs (P<0.05).

Conclusion

DNCs were demonstrated to be novel dual-targeted UCAs and may have potential applications in early non-invasive visualization of breast cancer.

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<![CDATA[NaCl: for the safer in vivo use of antibacterial silver based nanoparticles]]> https://www.researchpad.co/product?articleinfo=5bfb917ed5eed0c484af96ae

Background

As antibiotics progressively cease to be effective, silver based nanoparticles (SBNs), with broad antibacterial spectrum, might be the last line of defense against malicious bacteria. Unfortunately, there are still no proper SBNs-based strategies for in vivo antibacterial therapies. In this article, new carbon membrane packaged Ag nanoparticles (Ag-C) were synthesized. We assessed the effect of Ag-C with NaCl on size, cytotoxicity, antibacterial properties, metabolism and sepsis models.

Methods

The size of Ag-C with NaCl was accessed with UV-vis, TEM and SEM. Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were used to illustrate the antibacterial properties of SBNs affected by NaCl. L929 and 3T3 cell lines were cultured in vitro; CCK-8 assay was used to test cytotoxicity. Then, we explored the metabolism of Ag-C with NaCl in vivo. Finally, the effect of Ag-C with 4× NaCl on sepsis was observed.

Results

NaCl could regulate the size of Ag-C. Ag-C exhibited superior antibacterial properties compared to similar sized pure Ag nanoparticles. Furthermore, the addition of NaCl could not only reduce the cytotoxicity of Ag-C, but could also continue to discharge Ag-C from major organs. Based on these factors, this method was used to treat a sepsis model (induced via cecal ligation and puncture), and it achieved satisfactory survival results.

Conclusion

This discovery, though still in its infancy, could significantly improve the safety and feasibility of SBNs and could potentially play an important role in modern in vivo antibacterial applications. Thus, a new method to combating the growing threat from drug-resistant bacteria could be possible. NaCl is the key to excretion of SBNs after in vivo antibacterial use.

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<![CDATA[Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment]]> https://www.researchpad.co/product?articleinfo=5bfb30a4d5eed0c484962d3a

Background

Lung cancer is the primary cause of cancer-related death worldwide. A redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for improved lung cancer treatment.

Methods

The redox-sensitive nanocarrier system constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV) conjugate was synthesized and PTX was loaded in the delivery system. The physicochemical properties of the HSV nanoparticles were characterized. The redox-sensitivity, tumor-targeting and intracellular drug release capability of the HSV nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over-expressed A549 tumor model.

Results

This HSV conjugate was successfully synthesized and self-assembled to form nanoparticles in aqueous condition with a low critical micelle concentration of 36.3 μg mL−1. Free PTX was successfully entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV nanoparticles was confirmed by particle size change of the nanoparticles along with in vitro release profiles in different reducing environment. In addition, the HA-receptor mediated endocytosis and the potency of redox-sensitivity for intracellular drug delivery were further verified by flow cytometry and confocal laser scanning microscopic analysis. The antitumor activity results showed that compared to redox-insensitive nanoparticles and Taxol®, PTX-loaded redox-sensitive nanoparticles exhibited much greater in vitro cytotoxicity and apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo, the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an A549 mouse xenograft model and demonstrated improved safety profile. In summary, our PTX-loaded redox-sensitive HSV nanoparticles demonstrated enhanced antitumor efficacy and improved safety of PTX.

Conclusion

The results of our study indicated the redox-sensitive HSV nanoparticle was a promising nanocarrier for lung cancer therapy.

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