The protein corona formed on the surface of a nanoparticle in a biological medium determines its behavior in vivo. Herein, iron oxide nanoparticles containing the same core and shell, but bearing two ...different surface coatings, either glucose or poly(ethylene glycol), were evaluated. The nanoparticles’ protein adsorption, in vitro degradation, and in vivo biodistribution and biotransformation over four months were investigated. Although both types of nanoparticles bound similar amounts of proteins in vitro, the differences in the protein corona composition correlated to the nanoparticles biodistribution in vivo. Interestingly, in vitro degradation studies demonstrated faster degradation for nanoparticles functionalized with glucose, whereas the in vivo results were opposite with accelerated biodegradation and clearance of the nanoparticles functionalized with poly(ethylene glycol). Therefore, the variation in the degradation rate observed in vivo could be related not only to the molecules attached to the surface, but also with the associated protein corona, as the key role of the adsorbed proteins on the magnetic core degradation has been demonstrated in vitro.
Hybrid and composite nanoparticles represent an attractive material for enzyme integration due to possible synergic advantages of the structural builders in the properties of the nanobiocatalyst. In ...this study, we report the synthesis of a new stable hybrid nanobiocatalyst formed by biomimetic silica (Si) nanoparticles entrapping both Horseradish Peroxidase (HRP) (EC 1.11.1.7) and magnetic nanoparticles (MNPs). We have demonstrated that tailoring of the synthetic reagents and post immobilization treatments greatly impacted physical and biocatalytic properties such as an unprecedented ~280 times increase in the half-life time in thermal stability experiments. The optimized nanohybrid biocatalyst that showed superparamagnetic behaviour, was effective in the batch conversion of indole-3-acetic acid, a prodrug used in Direct Enzyme Prodrug Therapy (DEPT). Our system, that was not cytotoxic per se, showed enhanced cytotoxic activity in the presence of the prodrug towards HCT-116, a colorectal cancer cell line. The strategy developed proved to be effective in obtaining a stabilized nanobiocatalyst combining three different organic/inorganic materials with potential in DEPT and other biotechnological applications.
We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of ...rat colitis.
Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically.
The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone.
Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects.
Gliotoxin (GT), a secondary metabolite produced by Aspergillus molds, has been proposed as a potential anti-tumor agent. Here we have developed a nanoparticle approach to enhance delivery of GT in ...tumor cells and establish a basis for its potential use as therapeutical drug. GT bound to magnetic nanoparticles (MNPs) retained a high anti-tumor activity, correlating with efficient intracellular delivery, which was increased in the presence of glucose. Our results show that the attachment of GT to MNPs by covalent bonding enhances intracellular GT delivery without affecting its biological activity. This finding represents the first step to use this potent anti-tumor agent in the treatment of cancer.
Nanocarriers for chemo‐photothermal therapy suffer from insufficient retention at the tumor site and poor penetration into tumor parenchyma. A smart drug‐dye‐based micelle is designed by making the ...best of the structural features of small‐molecule drugs. P‐DOX is synthesized by conjugating doxorubicin (DOX) with poly(4‐formylphenyl methacrylate‐co‐2‐(diethylamino) ethyl methacrylate)‐b‐polyoligoethyleneglycol methacrylate (P(FPMA‐co‐DEA)‐b‐POEGMA) via imine linkage. Through the π–π stacking interaction, IR780, a near‐infrared fluorescence dye as well as a photothermal agent, is integrated into the micelles (IR780‐PDMs) with the P‐DOX. The IR780‐PDMs show remarkably long blood circulation (t1/2β = 22.6 h). As a result, a progressive tumor accumulation and retention are presented, which is significant to the sequential drug release. Moreover, when entering into a moderate acidic tumor microenvironment, IR780‐PDMs can dissociate into small‐size conjugates and IR780, which obviously increases the penetration depth of drugs, and then improves the lethality to deep‐seated tumor cells. Owing to the high delivery efficiency and superior chemo‐photothermal therapeutic efficacy of IR780‐PDMs, 97.6% tumor growth in the A549 tumor‐bearing mice is suppressed with a low dose of intravenous injection (DOX, 1.5 mg kg−1; IR780, 0.8 mg kg−1). This work presents a brand‐new strategy for long‐acting intensive cancer therapy.
A smart drug‐dye‐based micelle with long‐circulating ability and ultrahigh pH sensitivity is developed to optimize tumoral delivery efficiency via prolonged tumor accumulation and retention time, enhanced tumor penetration depth, and control of stimuli‐responsive drug release. The micelle shows superior chemo‐photothermal therapeutic efficacy and excellent biosafety after only a single‐dose treatment, which brings about a brand‐new strategy for long‐acting intensive cancer therapy.
The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive ...cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo-photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions (pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo-photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo-photodynamic system for theranostics of lung cancer, etc. in the near future.
Silver nanoparticles have particular properties that contribute to their very promising applications, novel in various fields of science, such as the development of biosensors, the diagnosis and ...treatment of cancer, the controlled release of drugs and the antimicrobial potential. The biological synthesis of nanoparticles is of great interest over other physical and chemical methods because the use of toxic chemicals and drastic reaction conditions are avoided. The extracellular biosynthesis using fungi could also make downstream processing much easier than the intracellular biosynthesis. One of the main applications of silver nanoparticles is their antimicrobial activity. Several studies have demonstrated the bactericidal properties of silver nanoparticles are different from silver ions, and that they are strongly influenced by their shape, size, concentration and colloidal state. In the present work, the ability of fungal strains from Uruguay to synthesize silver nanoparticles was studied. Eight fungi were able to synthesize nanoparticles. An extensive physicochemical characterization of the nanoparticles was carried out including ultraviolet-visible spectroscopy, transmission electron microscopy, dynamic light scattering, zeta-potential and gel electrophoretic mobility. According to the characterization and colloidal stability results, nanoparticles from three fungi were selected for antimicrobial activity assays. All nanoparticles were able to inhibit Escherichia coli growth, demonstrating their potential as effective antibacterial agent for use in biomedical applications.
Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating ...magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and magnetic hyperthermia as drug release and gene expression triggers for cancer therapy. Several strategies for the release of chemotherapeutic drugs from thermo-responsive matrices are discussed, providing representative examples of their application at different levels (from proof of concept to in vivo applications). The potential of magnetic hyperthermia to promote in situ expression of therapeutic genes using vectors that contain heat-responsive promoters is also reviewed in the context of cancer gene therapy.
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Concrete is one of the most commonly used construction materials in the world due to its versatility. There are different types of concrete according to the required mechanical responses, and these ...will depend on the composition of the elements. Therefore, additional elements have been developed to improve the properties and conditions of concrete. One of these elements is reinforcing fibers made of steel, polypropylene, glass, and so on, which, according to the base material, geometry, and dosage, improve the mechanical and workability properties and decrease and/or prevent the generation of cracks, which are some of the most common problems in industrial slabs. This study performs an analysis of the changes in the mechanical properties of concrete (compressive strength, rupture modulus, modulus of elasticity, Poisson’s ratio, and residual stress) due to the addition of fiber-reinforced concrete (FRC) to determine the physical and mechanical conditions of the fibers that improve the concrete and its application in industrial concrete. Due to the large number of samples and variables, advanced statistical methods (analysis of variance and comparative index) were used in the numerical study, which allowed to analyze and compare several results at the same time. This research is divided into two stages. In the first stage, six steel fibers (with a dosage of 2.7, 6, and 11 and three of 28 kg/m3) and five polypropylene fibers (with a dosage of 0.6, 2.15, and 2.7 and two of 3 kg/m3) were used in the study, and compression and bending tests (ASTM C39 and C78, respectively) were performed on 35 cylinders and 45 beams. Improvements were identified in several fiber-reinforced concrete samples in terms of compressive strength: 67% of the steel fiber samples and 100% of the polypropylene fiber samples had values above the average value of the simple concrete; in terms of the modulus of rupture, 83% of the steel fiber samples and 80% of the polypropylene fiber samples had values above the average value of the simple concrete. In the second stage, one type of steel fiber and one type of polypropylene fiber were selected for a second mechanical analysis (64 cylinders, 72 beams, and 15 slabs) with dosages of 20, 30, and 40 kg/m3 and 2.13, 4.25, and 6.38 kg/m3, respectively. In the second stage, statistical analysis and modeling with nonlinear analysis were used to evaluate the results, where residual strength improved but Poisson’s ratio decreased when the dosage of fibers was increased.
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