Tau- and α-synuclein-targeted gold nanoparticles: applications, opportunities, and future outlooks in the diagnosis and therapy of neurodegenerative diseases.

The use of nanomaterials in medicine offers multiple opportunities to address neurodegenerative disorders such as Alzheimer's and Parkinson's disease. These diseases are a significant burden for society and the health system, affecting millions of people worldwide without sensitive and selective diagnostic methodologies or effective treatments to stop their progression. In this sense, the use of gold nanoparticles is a promising tool due to their unique properties at the nanometric level. They can be functionalized with specific molecules to selectively target pathological proteins such as Tau and α-synuclein for Alzheimer's and Parkinson's disease, respectively. Additionally, these proteins are used as diagnostic biomarkers, wherein gold nanoparticles play a key role in enhancing their signal, even at the low concentrations present in biological samples such as blood or cerebrospinal fluid, thus enabling an early and accurate diagnosis. On the other hand, gold nanoparticles act as drug delivery platforms, bringing therapeutic agents directly into the brain, improving treatment efficiency and precision, and reducing side effects in healthy tissues. However, despite the exciting potential of gold nanoparticles, it is crucial to address the challenges and issues associated with their use in the medical field before they can be widely applied in clinical settings. It is critical to ensure the safety and biocompatibility of these nanomaterials in the context of the central nervous system. Therefore, rigorous preclinical and clinical studies are needed to assess the efficacy and feasibility of these strategies in patients. Since there is scarce and sometimes contradictory literature about their use in this context, the main aim of this review is to discuss and analyze the current state-of-the-art of gold nanoparticles in relation to delivery, diagnosis, and therapy for Alzheimer's and Parkinson's disease, as well as recent research about their use in preclinical, clinical, and emerging research areas.

Enhanced catalytic reduction of emerging contaminant by using magnetic CuFe2O4@MIL-100(Fe) in Fenton-based electrochemical processes.

Fenton-based electrochemical processes (FEPs) using newly engineered 3D photocatalyst nanocomposites have garnered significant attention owing to their ability to remove emerging contaminants. Despite the development of numerous materials, there is still a need to enhance their efficiency, stability, and recyclability to address the limitations of FEPs. This study seeks to address this issue by investigating sustainable methods to engineer novel 3D core-shell photocatalyst composites for application in FEPs. These materials can update the photo-assisted FEPs activity, and magnetism can be helpful for the easy recyclability of the catalyst. Herein, we successfully synthesized a magnetic and photoactive CuFe2O4@MIL-100(Fe) (CM) composite through sustainable methods and assessed its morphological structure and physicochemical and photocatalytic properties. The catalytic performance of CM was investigated in an undivided RuO2/air-diffusion cell to treat Cefadroxil. The results show that heterogeneous photoelectro-Fenton (HPEF) (100% in 120 min) has higher degradation efficiency than electro-Fenton (100% in 210 min) and electrooxidation (73.3% in 300 min) processes. The superior degradation efficiency of HPEF is attributed to the formation of a large amount of hydroxyl radicals indicating the excellent photocatalytic activity of the material due to the direct excitation of the Fe-O cluster, which boosts the redox reaction of Fe2+/Fe3+. Key operational parameters such as pH, catalyst concentration, current density, and CuFe2O4 proportion on MIL-100(Fe) in the composite were optimized in the HPEF process. The optimized composite exhibited good stability and easy recyclability, allowing high removal efficiency, which can be kept up after five cycles of 90 min. High degradation performance was observed using natural sunlight radiations. Additionally, possible catalytic degradation mechanisms in HPEFs were proposed based on radical quenching experiments. This study has significant potential to contribute to the development of more sustainable and effective water treatment strategies.

Nanostructured electrochemical sensor applied to the electrocoagulation of arsenite in WWTP effluent.

A sensitive electroanalytical method for the determination of arsenite, based on a heterostructure of aminated multiwalled carbon nanotubes and gold nanoparticles, was applied in an electrocoagulation (EC) treatment for the elimination of arsenite. A sensitive quantitative response was obtained in the determination of As3+ in a secondary effluent from a wastewater treatment plant from Santiago (Chile). The preconcentration stage was optimized through a Central Composite Face design, and the most sensitive peak current was obtained at 200 s and -600 mV of time and accumulation potential, respectively, after a differential pulse voltammetry sweep. Electroanalytical determination was possible in an interval between 42.89 and 170.00 µg L-1 with a detection limit of 0.39 µg L-1, obtaining recoveries over 99.1%. The developed method was successfully applied in an electrocoagulation treatment to remove 250 µg L-1 of arsenite from a polluted effluent in a batch system. Complete arsenite removal was achieved using a steel EC system with a current density of 6.0 mA cm-2 in less than 3 min of treatment.

High antibacterial performance of hydrophobic chitosan-based nanoparticles loaded with Carvacrol.

Bacterial infections have become one of the top ten public health concerns worldwide. These problems are aggravated with the emergence of multi-drug resistant bacterial strains. Thus, it is necessary to adopt novel technological strategies, such as development of bionanomaterials to prevent the infection, and treat this kind of bacteria. At this regard, the chemical modification of chitosan (Cs), by the covalent attachment of a hydrocarbon chain (octanoic acid), was developed to obtain hydrophobic chitosan (HCs). Then, HCs was used to synthetize nanoparticles using the well-known ionotropic gelation approach, optimizing the parameters, such as the TPP/HCs ratio and pH solution to get stable nanoparticles. Then, carvacrol (CAR) was loaded into NPs (HCs-CAR NPs) using different concentrations of 25%, 50% and 75% (%w/w CAR/HCs). The physicochemical properties for HCs-CAR NPs prepared at 50% of CAR stood out from the rest, showing a spherical morphology, with a size of 200 nm, Z potential of 10.4 mV and encapsulation efficiency of 56.28%. These formulations were chosen to evaluate the antibacterial activity, using Gram-negative (Escherichia coli) and Gram-positive bacterial model (Staphylococcus aureus). The HCs-CAR NPs showed great activity against both bacterial models, being more effective against Gram (+) strain (S. aureus), suggesting the potential application of these NPs as novel biomaterial to treat bacterial infection.

Study of the interaction of folic acid-modified gold nanorods and fibrinogen through microfluidics: implications for protein adsorption, incorporation and viability of cancer cells.

Gold nanoparticles (GNPs) are an attractive nanomaterial for potential applications in therapy and diagnostics due to their capability to direct toward specific sites in the organism. However, when exposed to plasma, GNPs can interact with different biomolecules that form a dynamic nano-bio interface called a "protein corona" (PC). Remarkably, the PC could affect multiple biological processes, such as cell targeting and uptake, cytotoxicity, and nanoparticle (NP) clearance. The interaction of nanomaterials with plasmatic proteins has been widely studied under bulk conditions, however, under dynamic conditions, it has just recently been explored. Thus, to mimic a dynamic natural environment found in arteries and veins, microfluidic devices were used. In this work, gold nanorods (GNRs) were synthesized and conjugated with polyethylene glycol (PEG) to reduce their interaction with plasma proteins and increase their biocompatibility. Then, GNRs were functionalized with folic acid, a targeting ligand typically used to recognize tumor cells. The resulting nanosystem was exposed to fibrinogen (FB) to study the development and biological impact of PC formation through two strategies: bulk and laminar flow conditions. The obtained nanosystems were characterized by absorption spectrophotometry, DLS, laser Doppler microelectrophoresis, neutron activation analysis, circular dichroism spectroscopy and TEM. Finally, cell viability and cellular uptake assays were performed to study the influence of the PC on the cell viability and delivery of nanosystems.

Microfluidics-assisted conjugation of chitosan-coated polymeric nanoparticles with antibodies: Significance in drug release, uptake, and cytotoxicity in breast cancer cells.

Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a polydimethylsiloxane (PDMS) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2), to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2 + breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties.

Copper-Modified Polymeric Membranes for Water Treatment: A Comprehensive Review.

In the last decades, the incorporation of copper in polymeric membranes for water treatment has received greater attention, as an innovative potential solution against biofouling formation on membranes, as well as, by its ability to improve other relevant membrane properties. Copper has attractive characteristics: excellent antimicrobial activity, high natural abundance, low cost and the existence of multiple cost-effective synthesis routes for obtaining copper-based materials with tunable characteristics, which favor their incorporation into polymeric membranes. This study presents a comprehensive analysis of the progress made in the area regarding modified membranes for water treatment when incorporating copper. The notable use of copper materials (metallic and oxide nanoparticles, salts, composites, metal-polymer complexes, coordination polymers) for modifying microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), forward osmosis (FO) and reverse osmosis (RO) membranes have been identified. Antibacterial and anti-fouling effect, hydrophilicity increase, improvements of the water flux, the rejection of compounds capacity and structural membrane parameters and the reduction of concentration polarization phenomena are some outstanding properties that improved. Moreover, the study acknowledges different membrane modification approaches to incorporate copper, such as, the incorporation during the membrane synthesis process (immobilization in polymer and phase inversion) or its surface modification using physical (coating, layer by layer assembly and electrospinning) and chemical (grafting, one-pot chelating, co-deposition and mussel-inspired PDA) surface modification techniques. Thus, the advantages and limitations of these modifications and their methods with insights towards a possible industrial applicability are presented. Furthermore, when copper was incorporated into membrane matrices, the study identified relevant detrimental consequences with potential to be solved, such as formation of defects, pore block, and nanoparticles agglomeration during their fabrication. Among others, the low modification stability, the uncontrolled copper ion releasing or leaching of incorporated copper material are also identified concerns. Thus, this article offers modification strategies that allow an effective copper incorporation on these polymeric membranes and solve these hinders. The article finishes with some claims about scaling up the implementation process, including long-term performance under real conditions, feasibility of production at large scale, and assessment of environmental impact.

Biodegradable photoresponsive nanoparticles for chemo-, photothermal- and photodynamic therapy of ovarian cancer.

Ovarian cancer (OC) is the deadliest gynecological cancer. Standard treatment of OC is based on cytoreductive surgery followed by chemotherapy with platinum drugs and taxanes; however, innate and acquired drug-resistance is frequently observed followed by a relapse after treatment, thus, more efficient therapeutic approaches are required. Combination therapies involving phototherapies and chemotherapy (the so-called chemophototherapy) may have enhanced efficacy against cancer, by attacking cancer cells through different mechanisms, including DNA-damage and thermally driven cell membrane and cytoskeleton damage. We have designed and synthesized poly(lactic-co-glycolic) nanoparticles (PLGA NPs) containing the chemo-drug carboplatin (CP), and the near infrared (NIR) photosensitizer indocyanine green (ICG). We have evaluated the drug release profile, the photodynamic ROS generation and photothermal capacities of the NPs. Also, the antitumoral efficiency of the NPs was evaluated using the SKOV-3 cell line as an in vitro OC model, observing an enhanced cytotoxic effect when irradiating cells with an 800 nm laser. Evidence here shown supports the potential application of the biodegradable photoresponsive NPs in the clinical stage due to the biocompatibility of the materials used, the spatiotemporal control of the therapy and, also, the less likely development of resistance against the combinatorial therapy.

Noble microfluidic system for bioceramic nanoparticles engineering.

Bioceramic nanoparticles have many potential applications within the biomedical device industry. However, these applications demand a precise control of their sizes, shapes and morphology which play a main role in most properties. In this work, we report a new route for the synthesis of hydroxyapatite nanoparticles using a microfluidic device. The process is carried out by continuous laminar flow through the device. The obtained nanoparticles have showed same properties (composition, length, orientation, roughness) than those produced by conventional methods, however, our device can afford to fine tune the structure via simple engineering, i.e., produce nanoparticles of different size only by varying the flow velocity. In addition to the efficiency and novelty of this system, the optimization of personnel costs makes it very profitable economically.

Easy, Quick, and Reproducible Sonochemical Synthesis of CuO Nanoparticles.

Copper oxide nanoparticles (CuO NPs) were synthesized in air by reducing copper (II) sulfate pentahydrate salt (CuSO4·5H2O) in the presence of sodium borohydride. The reaction was stabilized with Hexadecyltrimethylammonium bromide (CTAB) in a basic medium and using ultrasound waves. Different molar ratios of CTAB:Cu2+ and NaBH4:Cu2+ were explored, to optimize the synthesis conditions, and to study the stability, size, and Zeta potential of the colloidal suspension. Optimum conditions to generate spherical, stable, and monodispersed nanoparticles with hydrodynamic diameters of 36 ± 1.3 nm were obtained, using 16 mM CTAB and 2 M NaBH4 (molar ratios Cu2+:CTAB:NaBH4 of 1:6:10). X-ray diffraction (XRD) was implemented, and a monoclinic CuO crystal system was formed. This demonstrated a monoclinic crystal system corresponding to CuO. The diffraction peaks were identified and confirmed according to their selected area electron diffraction (SAED) patterns.

Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia.

BACKGROUND: Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated with systemic and neurological diseases. Despite the important role of poly (ADP-ribose) polymerase 1 (PARP-1) in the regulation of gene expression and DNA repair, overactivation of PARP-1 in asphyxia-exposed animals worsens the ATP-dependent energetic crisis. Inhibition of PARP-1 offers a therapeutic strategy for diminishing the effects of perinatal asphyxia. METHODS: We designed a nanosystem that incorporates a specific siRNA for PARP-1 knockdown. The siRNA was complexed with gold nanorods (AuNR) conjugated to the peptide CLPFFD for brain targeting. RESULTS: The siRNA was efficiently delivered into PC12 cells, resulting in gene silencing. The complex was administered intraperitoneally in vivo to asphyxia-exposed rat pups, and the ability of the AuNR-CLPFFD/siRNA complex to reach the brain was demonstrated. CONCLUSION: The combination of a nanosystem for delivery and a specific siRNA for gene silencing resulted in effective inhibition of PARP-1 in vivo.

Role of Biomacromolecules in Biomedical Engineering.

Biomacromolecules structures and their interaction between different systems have been extensively studied in the last years. Nevertheless, in the medicinal context, it has not been studied deeply. For this reason, the interest to investigate the behavior of different biomacromolecules such us proteins, organelles, phospholipids, etc. with soft materials has opened new research lines. Computational and experimental methodologies have tried to answer different questions that have been difficult to solve, due to the complexity of the phenomenon, as an example, competition between biomacromolecules and soft materials for a specific organ. In this review, we would like to demonstrate how soft materials influence the biomacromolecules structures and how to change their response, biodistribution and also biocompatibility for future applications.

Peptide multifunctionalized gold nanorods decrease toxicity of ß-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease.

The properties of nanometric materials make nanotechnology a promising platform for tackling problems of contemporary medicine. In this work, gold nanorods were synthetized and stabilized with polyethylene glycols and modified with two kinds of peptides. The D1 peptide that recognizes toxic aggregates of Aß, a peptide involved in Alzheimer's disease (AD); and the Angiopep 2 that can be used to deliver nanorods to the mammalian central nervous system. The nanoconjugates were characterized using absorption spectrophotometry, dynamic light scattering, and transmission electron microscopy, among other techniques. We determined that the nanoconjugate does not affect neuronal viability; it penetrates the cells, and decreases aggregation of Aß peptide in vitro. We also showed that when we apply our nanosystem to a Caenorhabditis elegans AD model, the toxicity of aggregated Aß peptide is decreased. This work may contribute to the development of therapies for AD based on metallic nanoparticles.

Gastric Cancer: Nanoparticles as Tools to Improve Treatment Efficacy.

In recent years, advances in nanotechnology have raised the specter of developing effective agents for the treatment of high-impact diseases, like gastric cancer, which remains one of the major causes of cancer deaths worldwide. This article reviews advances in the treatment of this pathology using several types of nanoparticles. First, we start with an overview of gastric cancer, its prevention, detection and the available treatments. Then, we discuss nanotechnology-based novel strategies using polymeric nanosystems, nanovesicular systems and inorganic nanoparticles. All of these systems are being evaluated in the perspective of improving the targeting of anticancer drugs and reducing their negative side effects.

Complex Behavior of Aqueous α-Cyclodextrin Solutions. Interfacial Morphologies Resulting from Bulk Aggregation.

The spontaneous aggregation of α-cyclodextrin (α-CD) molecules in the bulk aqueous solution and the interactions of the resulting aggregates at the liquid/air interface have been studied at 283 K using a battery of techniques: transmission electron microscopy, dynamic light scattering, dynamic surface tensiometry, Brewster angle microscopy, neutron reflectometry, and ellipsometry. We show that α-CD molecules spontaneously form aggregates in the bulk that grow in size with time. These aggregates adsorb to the liquid/air interface with their size in the bulk determining the adsorption rate. The material that reaches the interface coalesces laterally to form two-dimensional domains on the micrometer scale with a layer thickness on the nanometer scale. These processes are affected by the ages of both the bulk and the interface. The interfacial layer formed is not in fast dynamic equilibrium with the subphase as the resulting morphology is locked in a kinetically trapped state. These results reveal a surprising complexity of the parallel physical processes taking place in the bulk and at the interface of what might have seemed initially like a simple system.

Gold nanoparticles for photothermally controlled drug release.

In this article, we describe how nanoparticles work in photothermally triggered drug delivery, starting with a description of the plasmon resonance and the photothermal effect, and how this is used to release a drug. Then, we describe the four major functionalization strategies and each of their different applications. Finally, we discuss the biodistribution and toxicity of these systems and the necessary requirements for the use of gold nanoparticles for spatially and temporally controlling drug release through the photothermal effect.

Flow chemistry to control the synthesis of nano and microparticles for biomedical applications.

In this article we review the flow chemistry methodologies for the controlled synthesis of different kind of nano and microparticles for biomedical applications. Injection mechanism has emerged as new alternative for the synthesis of nanoparticles due to this strategy allows achieving superior levels of control of self-assemblies, leading to higher-ordered structures and rapid chemical reactions. Self-assembly events are strongly dependent on factors such as the local concentration of reagents, the mixing rates, and the shear forces, which can be finely tuned, as an example, in a microfluidic device. Injection methods have also proved to be optimal to elaborate microsystems comprising polymer solutions. Concretely, extrusion based methods can provide controlled fluid transport, rapid chemical reactions, and cost-saving advantages over conventional reactors. We provide an update of synthesis of nano and microparticles such as core/shell, Janus, nanocrystals, liposomes, and biopolymeric microgels through flow chemistry, its potential bioapplications and future challenges in this field are discussed.

Enhancing CaP biomimetic growth on TiO2 cuboids nanoparticles via highly reactive facets.

Pure decahedral anatase TiO(2) particles with high content of reactive {001} facets were obtained from titanium(IV) tetrachloride (TiCl(4)) using a microemulsions droplet system at specific conditions as chemical microreactor. The product was systematically characterized by X-ray diffraction, field-emission scanning and transmission electron microscopy (FE-SEM, TEM), N(2) adsorption-desorption isotherms, FT-IR and UV-vis spectroscopy, and photoluminescence studies. The obtained cuboids around 90 nm in size have a uniform and dense surface morphology with a BET specific surface area of 11.91 m(2) g(-1) and a band gap energy (3.18 eV) slightly inferior to the anatase dominated by the less-reactive {101} surface (3.20 eV). The presence of reactive facets on titania anatase favors the biomimetic growth of amorphous tricalcium phosphate after the first day of immersion in simulated human plasma. The results presented here can facilitate and improve the integration of anchored implants and enhance the biological responses to the soft tissues.