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The use of photothermal therapy (PTT) with the near-infrared II region (NIR-II: 1000-1700 nm) is expected to be a powerful cancer treatment strategy. It retains the noninvasive nature and excellent temporal and spatial controllability of the traditional PTT, and offers significant advantages in terms of tissue penetration depth, background noise, and the maximum permissible exposure standards for skin. MXenes, transition-metal carbides, nitrides, and carbonitrides are emerging inorganic nanomaterials with natural biocompatibility, wide spectral absorption, and a high photothermal conversion efficiency. The PTT of MXenes in the NIR-II region not only provides a valuable reference for exploring photothermal agents that respond to NIR-II in 2D inorganic nanomaterials, but also be considered as a promising biomedical therapy. First, the synthesis methods of 2D MXenes are briefly summarized, and the laser light source, mechanism of photothermal conversion, and evaluation criteria of photothermal performance are introduced. Second, the latest progress of PTT based on 2D MXenes in NIR-II are reviewed, including titanium carbide (Ti3 C2 ), niobium carbide (Nb2 C), and molybdenum carbide (Mo2 C). Finally, the main problems in the PTT application of 2D MXenes to NIR-II and future research directions are discussed.
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Hipertermia Inducida , Nanoestructuras , Terapia Fototérmica , Fototerapia/métodos , Hipertermia Inducida/métodos , Nanomedicina Teranóstica/métodosRESUMEN
Chirality plays a crucial function in the regulation of normal physiological processes and is widespread in organisms. Chirality can be imparted to nanomaterials, whether they are natural or manmade, through the process of asymmetric assembly and/or grafting of molecular chiral groups or linkers. Chiral inorganic nanomaterials possess unique physical and chemical features that set them apart from regular nanomaterials. They also have the ability to interact with cells and tissues in a specific manner, making them useful in various biomedical applications, particularly in the treatment of tumors. Despite the growing amount of research on chiral inorganic nanomaterials in the tumor microenvironment (TME) and their promising potential applications, there is a lack of literature that comprehensively summarizes the intricate interactions between chiral inorganic nanomaterials and TME. In this review, we introduce the fundamental concept, classification, synthesis methods, and physicochemical features of chiral inorganic nanomaterials. Next, we briefly outline the components of TME, such as T cells, macrophages, dendritic cells, and weak acids, and then discuss the anti-tumor effects of several chiral inorganic nanoparticles targeting these components and their potential for possible application during cancer therapy. Finally, the present challenges faced by chiral inorganic nanomaterials in cancer treatment and their future areas of investigation are disclosed.
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Nanoestructuras , Neoplasias , Microambiente Tumoral , Microambiente Tumoral/efectos de los fármacos , Humanos , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/química , EstereoisomerismoRESUMEN
Chlorogenic acid (CGA) that exhibits various bioactivities holds promise as a natural and safe medicinal agent or food supplement for promoting human health. However, the direct formulation for treatment is severely limited by its low water solubility, poor bioavailability, low plasma stability, and side effects caused by high doses. Fortunately, nanotechnology is widely applied for drug delivery to overcome the partial disadvantages of traditional drug molecules or naturally active components. The properties of CGA containing multiple hydroxyl groups as a green reductant and stabilizer have made the development of CGA-loaded nanomaterials possible. In this review, recent advancements in the design of CGA-loaded nanomaterials based on organic or inorganic nanomaterials were discussed, and the positive effects of nanomaterials on the release properties of active molecules and their targeted distribution in biological systems were indicated. These nanomaterials enhance the physiological activity of CGA in the treatment of various diseases. Moreover, in the field of food, CGA-loaded nanocomposites have been found to optimize the mechanical properties of nano-food packaging, leading to an extended shelf life of food products. The findings of this review provide a valuable foundation and reference for the development of novel CGA-loaded nanomedicines and nano-food packaging.
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Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.
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Sistemas de Liberación de Medicamentos , Fibrinolíticos , Trombosis , Humanos , Fibrinolíticos/química , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Trombosis/tratamiento farmacológico , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Terapia Trombolítica/métodos , AnimalesRESUMEN
Smart supercapacitors are a promising energy storage solution due to their high power density, long cycle life, and low-maintenance requirements. Functional polymers (FPs) and inorganic nanomaterials are used in smart supercapacitors because of the favorable mechanical properties (flexibility and stretchability) of FPs and the energy storage properties of inorganic materials. The complementary properties of these materials facilitate commercial applications of smart supercapacitors in flexible smart wearables, displays, and self-generation, as well as energy storage. Here, an overview of strategies for the development of suitable materials for smart supercapacitors is presented, based on recent literature reports. A range of synthetic techniques are discussed and it is concluded that a combination of organic and inorganic hybrid materials is the best option for realizing smart supercapacitors. This perspective facilitates new strategies for the synthesis of hybrid materials, and the development of material technologies for smart energy storage applications.
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Current approaches for electric power generation from nanoscale conducting or semiconducting layers in contact with moving aqueous droplets are promising as they show efficiencies of around 30%, yet even the most successful ones pose challenges regarding fabrication and scaling. Here, we report stable, all-inorganic single-element structures synthesized in a single step that generate electrical current when alternating salinity gradients flow along its surface in a liquid flow cell. Nanolayers of iron, vanadium, or nickel, 10 to 30 nm thin, produce open-circuit potentials of several tens of millivolt and current densities of several microA cm-2 at aqueous flow velocities of just a few cm s-1 The principle of operation is strongly sensitive to charge-carrier motion in the thermal oxide nanooverlayer that forms spontaneously in air and then self-terminates. Indeed, experiments suggest a role for intraoxide electron transfer for Fe, V, and Ni nanolayers, as their thermal oxides contain several metal-oxidation states, whereas controls using Al or Cr nanolayers, which self-terminate with oxides that are redox inactive under the experimental conditions, exhibit dramatically diminished performance. The nanolayers are shown to generate electrical current in various modes of application with moving liquids, including sliding liquid droplets, salinity gradients in a flowing liquid, and in the oscillatory motion of a liquid without a salinity gradient.
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Cancer is a genetic disease originating from the accumulation of gene mutations in a cellular subpopulation. Although many therapeutic approaches have been developed to treat cancer, recent studies have revealed an irrefutable challenge that tumors evolve defenses against some therapies. Gene therapy may prove to be the ultimate panacea for cancer by correcting the fundamental genetic errors in tumors. The engineering of nanoscale inorganic carriers of cancer therapeutics has shown promising results in the efficacious and safe delivery of nucleic acids to treat oncological diseases in small-animal models. When these nanocarriers are used for co-delivery of gene therapeutics along with auxiliary treatments, the synergistic combination of therapies often leads to an amplified health benefit. In this review, an overview of the inorganic nanomaterials developed for combinatorial therapies of gene and other treatment modalities is presented. First, the main principles of using nucleic acids as therapeutics, inorganic nanocarriers for medical applications and delivery of gene/drug payloads are introduced. Next, the utility of recently developed inorganic nanomaterials in different combinations of gene therapy with each of chemo, immune, hyperthermal, and radio therapy is examined. Finally, current challenges in the clinical translation of inorganic nanomaterial-mediated therapies are presented and outlooks for the field are provided.
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Synthesis of inorganic nanomaterials such as metal nanoparticles (MNPs) using various biological entities as smart nanofactories has emerged as one of the foremost scientific endeavors in recent years. The biosynthesis process is environmentally friendly, cost-effective and easy to be scaled up, and can also bring neat features to products such as high dispersity and biocompatibility. However, the biomanufacturing of inorganic nanomaterials is still at the trial-and-error stage due to the lack of understanding for underlying mechanism. Dissimilatory metal reduction bacteria, especially Shewanella and Geobacter species, possess peculiar extracellular electron transfer (EET) features, through which the bacteria can pump electrons out of their cells to drive extracellular reduction reactions, and have thus exhibited distinct advantages in controllable and tailorable fabrication of inorganic nanomaterials including MNPs and graphene. Our aim is to present a critical review of recent state-of-the-art advances in inorganic biosynthesis methodologies based on bacterial EET using Shewanella and Geobacter species as typical strains. We begin with a brief introduction about bacterial EET mechanism, followed by reviewing key examples from literatures that exemplify the powerful activities of EET-enabled biosynthesis routes towards the production of a series of inorganic nanomaterials and place a special emphasis on rationally tailoring the structures and properties of products through the fine control of EET pathways. The application prospects of biogenic nanomaterials are then highlighted in multiple fields of (bio-) energy conversion, remediation of organic pollutants and toxic metals, and biomedicine. A summary and outlook are given with discussion on challenges of bio-manufacturing with well-defined controllability.
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Transporte de Electrón , Electrones , Tecnología Química Verde/métodos , Nanoestructuras/química , Antiinfecciosos/química , Bacterias , Electrodos , Grafito , Nanopartículas del Metal/química , Metales/química , Técnicas Microbiológicas/métodos , Shewanella/química , Shewanella/metabolismoRESUMEN
Hansen solubility parameters (HSPs) were established by Hansen in 1967 and predict miscibility between different material systems. So far, HSP theory works across polymers, crystalline bulk solids and nanomaterials and can be used to identify single solvents or, more likely, blends of solvents that deliver not only the initial solubility but also control it during reaction processes. This minireview summarizes the recent progress on HSP theory to optimize dispersion, exfoliation, synthesis, and device fabrication of inorganic nanomaterials. First, we briefly introduce HSP theory and determination of HSPs. Then, we discuss in detail the utilization of HSPs for inorganic nanomaterials, focusing on carbon nanomaterials, two-dimensional non-graphene nanomaterials, and metal oxide nanoparticles. Finally, challenges and perspectives of HSP theory in inorganic nanomaterials are reviewed.
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A non-enzymatic fluorometric assay is described for the determination of glucose. The method is based on the use of g-C3N4 quantum dots (QDs) that have good water solubility. The QDs were synthesized by a one-step solvothermal process using formamide as precursor. The QDs possess an average size of ~5 nm, a band gap of 3.0~3.5 eV, and strong blue fluorescence (with excitation/emission maxima at 400/447 nm). Fluorescence is quenched by glucose (which acts as the electron acceptor) via an electron transfer mechanism. Comprehensive spectroscopy and density functional theory calculations show that the selectivity of the fluorescent probe can be attributed to the presence of N-H bonds that are formed between the QDs (mainly at plane edges) and glucose. The interaction forces lead to the formation of localized states for capturing hot electrons. This results in a decrease in the band gap and a reduction in fluorescence intensity. The probe is selective over some typical interfering species (such as cysteine and albumin) which often are present in the urine of diabetics. The method has a linear response in the 0.2 to 5.0 mM glucose concentration range and a 0.2 mM detection limit. Graphical abstractSchematic representation of the synthesis of g-C3N4 quantum dots (QDs) as a fluorescent nanoprobe for selective detection of glucose.
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Colorantes Fluorescentes/química , Glucosuria/sangre , Grafito/química , Compuestos de Nitrógeno/química , Puntos Cuánticos/química , Espectrometría de Fluorescencia/métodos , Bebidas/análisis , Teoría Funcional de la Densidad , Humanos , Límite de Detección , Modelos QuímicosRESUMEN
In recent years, an increasing number of nanomaterials have been explored for their applications in biomedical diagnostics, making their applications in healthcare biosensing a rapidly evolving field. Nanomaterials introduce versatility to the sensing platforms and may even allow mobility between different detection mechanisms. The prospect of a combination of different nanomaterials allows an exploitation of their synergistic additive and novel properties for sensor development. This paper covers more than 290 research works since 2015, elaborating the diverse roles played by various nanomaterials in the biosensing field. Hence, we provide a comprehensive review of the healthcare sensing applications of nanomaterials, covering carbon allotrope-based, inorganic, and organic nanomaterials. These sensing systems are able to detect a wide variety of clinically relevant molecules, like nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals and narcotic drugs, toxins, contaminants, as well as entire cells in various sensing media, ranging from buffers to more complex environments such as urine, blood or sputum. Thus, the latest advancements reviewed in this paper hold tremendous potential for the application of nanomaterials in the early screening of diseases and point-of-care testing.
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Técnicas Biosensibles/métodos , Nanoestructuras/química , HumanosRESUMEN
A nanozyme composed of mesoporous silica and platinum nanoparticles (MS-PtNPs) was synthesized and is shown to display peroxidase-like activity. Its activity can be controlled by loading with single-stranded DNA. The PtNPs on the MS are homogeneously distributed and act as enzyme mimics. The adsorption of DNA probe on the MS blocks the nucleation sites of PtNPs. This leads to a decrease in the peroxidase-mimicking activity. After introduction of target DNA that is complementary to the DNA probe, the activity of the nanozyme is recovered. By using the 3,3,5,5-tetramethylbenzidine/H2O2 chromogenic system, a rapid method was developed for colorimetric determination of DNA. The assay, best performed at 450 nm, has a linear response in the 5 nM to 100 nM DNA concentration range and a 2.6 nM detection limit. It possesses high selectivity and can distinguish even a single-base mismatch. Graphical abstract The peroxidase-like activity of mesoporous silica and platinum nanoparticles (MS-PtNPs) was depressed when noncovalent ssDNA-MS was in-situ deposited on the PtNPs. After introduction of target DNA, the complementary dsDNA releases from the MS, and then its activity is recovered.
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Materiales Biomiméticos/química , Colorimetría/métodos , ADN/análisis , Nanopartículas del Metal/química , Peroxidasa/metabolismo , Platino (Metal)/química , Dióxido de Silicio/química , ADN/química , Oro/química , Modelos Moleculares , Conformación Molecular , PorosidadRESUMEN
Protein pharmaceuticals show great therapeutic promise, but effective intracellular delivery remains challenging. To address the need for efficient protein transduction systems, we used a magnetic nanogel chaperone (MC): a hybrid of a polysaccharide nanogel, a protein carrier with molecular chaperone-like properties, and iron oxide nanoparticles, enabling magnetically guided delivery. The MC complexed with model proteins, such as BSA and insulin, and was not cytotoxic. Cargo proteins were delivered to the target HeLa cell cytosol using a magnetic field to promote movement of the protein complex toward the cells. Delivery was confirmed by fluorescence microscopy and flow cytometry. Delivered ß-galactosidase, inactive within the MC complex, became enzymatically active within cells to convert a prodrug. Thus, cargo proteins were released from MC complexes through exchange interactions with cytosolic proteins. The MC is a promising tool for realizing the therapeutic potential of proteins.
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Portadores de Fármacos/química , Compuestos Férricos/química , Nanopartículas del Metal/química , Polietilenglicoles/química , Polietileneimina/química , Proteínas/metabolismo , Animales , Bovinos , Colorantes Fluorescentes/química , Glucanos/química , Células HeLa , Humanos , Insulina/química , Insulina/metabolismo , Magnetismo , Microscopía Confocal , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Nanogeles , Proteínas/química , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismoRESUMEN
Inorganic nanomaterials have a wide array of physical and structural properties that make them attractive candidates for imaging and therapeutic delivery. Nanoparticle platforms have been intensely studied for these applications, and examples are starting to enter the clinic. This review looks at why inorganic particles provide promising platforms for biomedicine, and what issues need to be addressed for them to reach their potential.
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Theranostic nanoparticles (NPs) have the potential to dramatically improve cancer management by providing personalized medicine. Inorganic NPs have attracted widespread interest from academic and industrial communities because of their unique physicochemical properties (including magnetic, thermal, and catalytic performance) and excellent functions with functional surface modifications or component dopants (e.g., imaging and controlled release of drugs). To date, only a restricted number of inorganic NPs are deciphered into clinical practice. This review highlights the recent advances of inorganic NPs in breast cancer therapy. We believe that this review can provides various approaches for investigating and developing inorganic NPs as promising compounds in the future prospects of applications in breast cancer treatment and material science.
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Antineoplásicos , Neoplasias de la Mama , Nanopartículas , Nanomedicina Teranóstica , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Animales , Medicina de PrecisiónRESUMEN
Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed.
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Neoplasias de la Mama , Nanopartículas Magnéticas de Óxido de Hierro , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Nanopartículas Magnéticas de Óxido de Hierro/química , Sistemas de Liberación de Medicamentos/métodos , Propiedades de Superficie , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Animales , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Microambiente Tumoral/efectos de los fármacosRESUMEN
"Nanozymes" usually refers to inorganic nanomaterials with enzyme-like catalytic activities. The research into nanozymes is one of the hot topics on the horizon of interdisciplinary science involving materials, chemistry, and biology. Although great progress has been made in the design, synthesis, characterization, and application of nanozymes, the study of the underlying microscopic mechanisms and kinetics is still not straightforward. Density functional theory (DFT) calculations compute the potential energy surfaces along the reaction coordinates for chemical reactions, which can give atomistic-level insights into the micro-mechanisms and kinetics for nanozymes. Therefore, DFT calculations have been playing an increasingly important role in exploring the mechanisms and kinetics for nanozymes in the past years. The calculations either predict the microscopic details for the catalytic processes to complement the experiments or further develop theoretical models to depict the physicochemical rules. In this review, the corresponding research progress is summarized. Particularly, the review focuses on the computational studies that closely interplay with the experiments. The relevant experimental results without DFT calculations will be also briefly discussed to offer a historic overview of how the computations promote the understanding of the microscopic mechanisms and kinetics of nanozymes.
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BACKGROUND: A nano drug delivery system is an effective tool for drug delivery and controlled release, which is used for a variety of medical applications. In recent decades, nano drug delivery systems have been significantly developed with the emergence of new nanomaterials and nanotechnologies. OBJECTIVE: This article aimed to provide insight into the technological development of nano drug delivery systems through patent analysis. METHODS: 3708 patent documents were used for patent analysis after retrieval from the Incopat patent database. RESULTS: The number of patents on nano drug delivery systems has shown a rapid growth trend in the past two decades. At present, China and the United States have obvious contributions to the number of patents. According to the patent data, the nanomaterials used in nano drug delivery system are mainly inorganic nanomaterials, lipid-based nanomaterials, and macromolecules. In recent years, the highly cited patents (≥14) for nano drug delivery systems mainly involve lipid-based nanomaterials, indicating that their technology is mature and widely used. The inorganic nanomaterials in drug delivery have received increasing attention, and the number of related patents has increased significantly after 2016. The number of highly cited patents in the United States is 250, which is much higher than in other countries. CONCLUSION: Even after decades of development, nano drug delivery systems remain a hot topic for researchers. The significant increase in patents since 2016 can be attributed to the large number of new patents from China. However, according to the proportion of highly cited patents in total, China's patented technologies in nano drug delivery systems are not advanced enough compared to developed countries, including the United States, Canada, Germany, and France. In the future, research on emerging nanomaterials for nano drug delivery systems, such as inorganic nanomaterials, may focus on developing new materials and optimising their properties. The lipid-based and polymer- based nanomaterials can be continuously improved for the development of new nanomedicines.
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OBJECTIVES: Dental biofilm is one of the most prevalent diseases in humans, which is mediated by multiple microorganisms. Globally, half of the human population suffers from dental biofilm and its associated diseases. In recent trends, nano-formulated drugs are highly attractive in the treatment of dental biofilms. However, the impact of different types of nanodrugs on the dental biofilm and its associated pathogens have not been published till date. Thus, this review focuses on the recent updates, feasibility, mechanisms, limitations, and regulations of nanodrugs applications in the prevention and eradication of dental biofilm. STUDY SELECTION, DATA AND SOURCES: A systematic search was conducted in PubMed/Google Scholar/Scopus over the past five years covering the major keywords "nanodrugs, metallic nanoparticles, metal oxide nanoparticles, natural polymers, synthetic polymers, biomaterials, dental biofilm, antibiofilm mechanism, dental pathogens", are reviewed in this study. Nearly, 100 scientific articles are selected in this relevant topic published between 2019 and 2023. Data from the selected studies dealing with nanodrugs used for biofilm treatment was qualitatively analyzed. CONCLUSIONS: The nanodrugs such as silver nanoparticles, gold nanoparticles, selenium nanoparticles, zinc oxide nanoparticles, copper oxide nanoparticles, titanium oxide nanoparticles, hydroxyapatite nanoparticles and these inorganic nanoparticles incorporated polymer-based nanocomposites, organic/inorganic nanoparticles mediated antimicrobial photodynamic therapy exhibits an excellent antibacterial and antibiofilm activity towards dental pathogens. Finally, this review highlights that bioinspired nanodrugs will be very useful to control the dental biofilm and its associated diseases. CLINICAL SIGNIFICANCE: Microbial influence on the oral environment is unavoidable; therefore, curing such dental biofilms and pathogens is essential for the impactful reflection of applying biocompatible treatments. In this direction, the current review explains the demand for the nanodrug in inhibiting biofilms for the effective exploration of employing treatments.
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Biopelículas , Biopelículas/efectos de los fármacos , Humanos , Nanopartículas del Metal/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , NanopartículasRESUMEN
Since 2020, the REACh regulation requires toxicological data on nanoforms of materials, including the assessment of their skin-sensitizing properties. Small molecules' skin sensitization potential can be assessed by new approach methodologies (NAMs) addressing three key events (KE: protein interaction, activation of dendritic cells, and activation of keratinocytes) combined in a defined approach (DA) described in the OECD guideline 497. In the present study, the applicability of three NAMs (DPRA, LuSens, and h-CLAT) to nine materials (eight inorganic nanomaterials (NM) consisting of CeO2, BaSO4, TiO2 or SiO2, and quartz) was evaluated. The NAMs were technically applicable to NM using a specific sample preparation (NANOGENOTOX dispersion protocol) and method modifications to reduce interaction of NM with the photometric and flowcytometric read-outs. The results of the three assays were combined according to the defined approach described in the OECD guideline No. 497; two of the inorganic NM were identified as skin sensitizers. However, data from animal studies (for ZnO, also human data) indicate no skin sensitization potential. The remaining seven test substances were assessed as "inconclusive" because all inorganic NM were outside the domain of the DPRA, and the achievable test concentrations were not sufficiently high according to the current test guidelines of all three NAMs. The use of these NAMs for (inorganic) NM and the relevance of the results in general are challenged in three ways: (i) NAMs need modification to be applicable to insoluble, inorganic matter; (ii) current test guidelines lack adequate concentration metrics and top concentrations achievable for NM; and (iii) NM may not cause skin sensitization by the same molecular and cellular key events as small organic molecules do; in fact, T-cell-mediated hypersensitivity may not be the most relevant reaction of the immune system to NM. We conclude that the NAMs adopted by OECD test guidelines are currently not a good fit for testing inorganic NM.