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Infections associated with medical implants due to bacterial adhesion and biofilm formation are a serious problem, leading to acute health risks to patients by compromising their immune system. Therefore, suppressing biofilm formation on biomedical implants is a challenging task, especially for overcoming the drug resistance of bacterial biofilms. Herein, a synergistic efficient surface coating method was developed to inhibit biofilm formation on a model medical implant by combining the antimicrobial property of trimethyl chitosan (TMC) with either 2D material graphene oxide (GO) or black phosphorus (BP) sheets using layer-by-layer (LbL) self-assembly. The multilayer coatings of TMC/GO and TMC/BP were optimized on the glass surface (a model implant) and characterized by using spectroscopic and microscopy techniques. Next, we investigated the antibiofilm formation properties of the TMC/GO and TMC/BP coatings on glass surfaces against both Gram-negative, Escherichia coli (E. coli), and Gram-positive, Bacillus subtilis (B. subtilis), bacteria. The antibiofilm formation was studied using crystal violet (CV) and live/dead assays. Both the live/dead and the CV assays confirmed that the TMC/2D material (2DM)-coated surfaces prevented biofilm formation much more effectively compared to the uncoated surfaces. Scanning electron microscopy analyses revealed that the bacteria were affected physically by incubating with TMC/2DM-coated surfaces due to membrane perturbation, thereby preventing cell attachment and biofilm formation. Further, BP composite coatings (TMC/BP) showed a much better ability to thwart biofilm formation than GO composite coatings (TMC/GO). Also, multilayer coatings showed superior cytocompatibility with human foreskin fibroblast (HFF). Our results demonstrate that the developed coatings TMC/2DMs could be potential candidates for thwarting biofilm formation on medical implants.
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The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is pivotal in orchestrating the immune response induced by nanoparticle adjuvants. Understanding the intricate mechanisms underlying the activation of NLRP3 inflammasome by these adjuvants is crucial for deciphering their immunomodulatory properties. This review explores the involvement of the NLRP3 inflammasome in mediating immune responses triggered by nanoparticle adjuvants. It delves into the signaling pathways and cellular mechanisms involved in NLRP3 activation, highlighting its significance in modulating the efficacy and safety of nanoparticle-based adjuvants. A comprehensive grasp of the interplay between NLRP3 inflammasome and nanoparticle adjuvants holds promise for optimizing vaccine design and advancing immunotherapeutic strategies.
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Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. The primary obstacle lies in the absence of an optimal delivery system, which significantly hampers the immunogenicity of DNA vaccines. We conduct a comprehensive analysis of the current status and limitations of DNA vaccines by focusing on both viral and non-viral DNA delivery systems, as they play crucial roles in the exploration of novel DNA vaccines. We provide an evaluation of their strengths and weaknesses based on our critical assessment. Additionally, the review summarizes the most recent advancements and breakthroughs in pre-clinical and clinical studies, highlighting the need for further clinical trials in this rapidly evolving field.
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Vacinas de DNA , Animais , Humanos , Sistemas de Liberação de Medicamentos , Modelos AnimaisRESUMO
Developing a biocompatible and biodegradable graphene-based fluorescent nanoprobe with the ability to visualize live cells could be interesting for intracellular imaging and monitoring the efficiency of chemotherapy. Herein, we report a biodegradable and biocompatible hybrid fluorescent graphene oxide (GO)-ZnS(Mn) composite synthesized via in situ growth of ZnS(Mn) quantum dots (QDs) on the surface of GO in the aqueous medium. The prepared 'GO-ZnS(Mn)' composite was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and high-resolution transmission electron microscopy (HR-TEM) along with selected area electron diffraction (SAED). Further, the fluorescence properties of the GO-ZnS(Mn) composite were studied using fluorescence emission spectroscopy. The composite material exhibited a strong and broad visible light fluorescence from 500 to 600 nm by excitation with 365 nm (UV) light. The cytotoxic experiments of folic acid (FA) conjugated GO-ZnS(Mn) using MTT [(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)] assay revealed that the composite had excellent biocompatibility even at higher concentrations up to 200 µg/mL in HeLa cell lines. Next, the bioimaging experiments carried out using confocal fluorescence laser scanning microscopy (CLSM) revealed that GO-ZnS(Mn) composite was taken up by the HeLa cells effectively within 12 h of incubation via receptor (folate) mediated endocytosis with strong fluorescence throughout the cell surface. Finally, the biodegradability of GO-ZnS(Mn) composite was studied by treating it with human myeloperoxidase enzyme (hMPO) isolated from the primary immune cells, neutrophils, which is important to understand the in vivo fate of GO-Zns(Mn). The HR-TEM and Raman analyses confirmed the biodegradation of GO-ZnS(Mn) within 15 h of hMPO treatment. Thus, the biodegradable GO-ZnS (Mn) composite could be helpful for chemotherapy and bioimaging applications.
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Grafite , Nanocompostos , Pontos Quânticos , Humanos , Pontos Quânticos/química , Células HeLa , Grafite/química , Nanocompostos/químicaRESUMO
Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced technologies for the highly efficient in vivo delivery of exogenous mRNA, particularly for COVID-19 vaccine delivery. LNPs comprise four different lipids: ionizable lipids, helper or neutral lipids, cholesterol, and lipids attached to polyethylene glycol (PEG). In this review, we present recent the advances and insights for the design of LNPs, as well as their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as ionizable lipids are the most critical drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines is discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy is explained. Finally, expert opinion on LNPs for mRNA vaccines is discussed, which may address future challenges in developing mRNA vaccines using highly efficient LNPs based on a novel set of ionizable lipids. Developing highly efficient mRNA delivery systems for vaccines with improved safety against some severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains difficult.
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Water-dispersible two-dimensional (2D) materials are desirable for diverse applications. Aqueous dispersions make processing safer and greener and enable evaluation of these materials on biological and environmental fronts. To evaluate the effects of 2D materials with biological systems, obtaining dispersions without additives is critical and has been a challenge. Herein, a method was developed for obtaining additive-free aqueous dispersions of 2D materials like transition metal dichalcogenides and hexagonal boron nitride (h-BN). The nanosheet dispersions were investigated through spectroscopic and microscopic methods, along with the role of size on stability. The aqueous media enabled investigations on cytocompatibility and enzymatic degradation of molybdenum disulphide (MoS2 ) and h-BN. Cytocompatibility with mixed glial cells was observed up to concentrations of 100â µg mL-1 , suggesting their plausible usage in bioelectronics. Besides, biodegradation using human myeloperoxidase (hMPO) mediated catalysis was investigated through Raman spectroscopy and electron microscopy. The findings suggested that additive-free 2H-MoS2 and h-BN were degradable by hMPO, with 2H-phase exhibiting better resistance to degradation than the 1T-phase, while h-BN exhibited slower degradation. The findings pave a path for incorporating 2D materials in the burgeoning field of transient bioelectronics.
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Análise Espectral Raman , Água , Catálise , Humanos , NeurogliaRESUMO
Understanding the biodegradability of graphene materials by the action of oxidative enzymes secreted by immune cells is essential for developing applicable biomedical products based on these materials. Herein, we demonstrate the biodegradation of graphene oxide (GO) by recombinant eosinophil peroxidase (EPO) enzyme extracted from human eosinophils in the presence of a low concentration of hydrogen peroxide and NaBr. We compared the degradation capability of the enzyme on three different GO samples containing different degrees of oxygen functional groups on their graphenic lattices. EPO succeeded in degrading the three tested GO samples within 90 h treatment. Raman spectroscopy and transmission electron microscopy analyses provided clear-cut evidence for the biodegradation of GO by EPO catalysis. Our results provide more insight into a better understanding of the biodegradation of graphene materials, helping the design of future biomedical products based on these carbon nanomaterials.
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Grafite , Nanoestruturas , Catálise , Peroxidase de Eosinófilo , Humanos , Análise Espectral RamanRESUMO
A large number of graphene and other 2D materials are currently used for the development of new technologies, increasingly entering different industrial sectors. Interrogating the impact of such 2D materials on health and environment is crucial for both modulating their potential toxicity in living organisms and eliminating them from the environment. In this context, understanding if 2D materials are bio-persistent is mandatory. In this review we describe the importance of biodegradability and decomposition of 2D materials. We initially cover the biodegradation of graphene family materials, followed by other emerging classes of 2D materials including transition metal dichalcogenides and oxides, Xenes, Mxenes and other non-metallic 2D materials. We explain the role of defects and functional groups, introduced onto the surface of the materials during their preparation, and the consequences of chemical functionalization on biodegradability. In strong relation to the chemistry on 2D materials, we describe the concept of "degradation-by-design" that we contributed to develop, and which concerns the covalent modification with appropriate molecules to enhance the biodegradability of 2D materials. Finally, we cover the importance of designing new biodegradable 2D conjugates and devices for biomedical applications as drug delivery carriers, in bioelectronics, and tissue engineering. We would like to highlight that the biodegradation of 2D materials mainly depends on the type of material, the chemical functionalization, the aqueous dispersibility and the redox potentials of the different oxidative environments. Biodegradation is one of the necessary conditions for the safe application of 2D materials. Therefore, we hope that this review will help to better understand their biodegradation processes, and will stimulate the chemists to explore new chemical strategies to design safer products, composites and devices containing 2D materials.
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Materiais Biocompatíveis , Biodegradação Ambiental , Sistemas de Liberação de Medicamentos , GrafiteRESUMO
Layer-by-layer (LbL) assembly of polyelectrolytes to multifunctional polyelectrolyte multilayer hollow capsules (PMCs) with a core-shell structure is now a well-established method. PMCs have been shown to have several potential applications including their application as drug delivery vehicles with controlled and targeted drug release. Along with polyelectrolytes, inorganic materials such as nanoparticles and ligands can be used to make the capsules respond to certain stimuli and also target them to specific sites. In this special issue devoted to biomaterials development in India, we focus on bringing some of the research done by our group in the past 15 years related to LbL methodology for drug delivery applications, especially using PMCs. Our contributions to stimuli-responsive LbL capsules and nanomaterial-based capsules will be highlighted. Also, the use of LbL methodology for probiotics will be presented. We believe that LbL methodology is a very versatile tool for engineering hollow capsules and surfaces, which can be used in many applications including drug delivery.
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DNAzymes made of supramolecular guanine-rich G-quadruplexes and hemin are attracting a lot of interest due to their peroxidase activity mimicking the natural enzyme horseradish peroxidase (HRP). Herein, we demonstrate that DNAzyme consisting of a PS2.M-hemin complex can be an alternative to natural HRP for the oxidation and degradation of graphene oxide (GO). The degradation of GO sheets was carried out by incubating the PS2.M-hemin complex in the presence of hydrogen peroxide for 30 days. The degradation of GO has been confirmed using transmission electron microscopy and 2d Raman mapping. The current study suggests that the peroxidase activity of DNAzymes is similar to HRP and DNAzymes are able to degrade carbon-based nanomaterials.
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Materiais Biocompatíveis/metabolismo , Grafite/metabolismo , Peroxidase do Rábano Silvestre/metabolismo , Materiais Biocompatíveis/química , DNA Catalítico/química , DNA Catalítico/metabolismo , Quadruplex G , Hemina/química , Hemina/metabolismo , Peroxidase do Rábano Silvestre/química , Peróxido de Hidrogênio/química , Microscopia Eletrônica de Transmissão , Oligonucleotídeos/química , Análise Espectral RamanRESUMO
Biodegradability of graphene is one of the fundamental parameters determining the fate of this material inâ vivo. Two types of aqueous dispersible graphene, corresponding to single-layer (SLG) and few-layer graphene (FLG), devoid of either chemical functionalization or stabilizing surfactants, were subjected to biodegradation by human myeloperoxidase (hMPO) mediated catalysis. Graphene biodegradation was also studied in the presence of activated, degranulating human neutrophils. The degradation of both FLG and SLG sheets was confirmed by Raman spectroscopy and electron microscopy analyses, leading to the conclusion that highly dispersed pristine graphene is not biopersistent.
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Poluentes Ambientais/metabolismo , Grafite/metabolismo , Peroxidase/metabolismo , Biodegradação Ambiental , Poluentes Ambientais/química , Proteínas Filagrinas , Grafite/química , Humanos , Neutrófilos/enzimologia , Neutrófilos/metabolismo , Análise Espectral RamanRESUMO
Currently, a broad interdisciplinary research effort is pursued on biomedical applications of 2D materials (2DMs) beyond graphene, due to their unique physicochemical and electronic properties. The discovery of new 2DMs is driven by the diverse chemical compositions and tuneable characteristics offered. Researchers are increasingly attracted to exploit those as drug delivery systems, highly efficient photothermal modalities, multimodal therapeutics with non-invasive diagnostic capabilities, biosensing, and tissue engineering. A crucial limitation of some of the 2DMs is their moderate colloidal stability in aqueous media. In addition, the lack of suitable functionalisation strategies should encourage the exploration of novel chemical methodologies with that purpose. Moreover, the clinical translation of these emerging materials will require undertaking of fundamental research on biocompatibility, toxicology and biopersistence in the living body as well as in the environment. Here, a thorough account of the biomedical applications using 2DMs explored today is given.
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Hexagonal boron nitride (hBN) nanosheets are emerging as promising 2D materials for different types of applications. However, biodegradation of hBN materials is poorly explored owing to their high chemical inertness and strong oxidation resistance. The assessment of oxidation/biodegradation of hBN is important in developing biomedical tools. Herein, we report the first study on the biodegradability of hBN nanosheets comparing the enzymatic catalysis of two different peroxidases, horseradish peroxidase (HRP) and human myeloperoxidase (MPO), with the photo-Fenton (P.F.) reaction. The results show that degradation of hBN nanosheets is different to that of graphene and graphene oxide, since partial oxidation was found using MPO after 35â h, while HRP failed to degrade hBN up to 60â days. Nearly complete oxidation/degradation was occurred by P.F. reaction in 100â h. These results are helpful in designing advanced conjugates for biomedical uses of hBN.
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Compostos de Boro/química , Grafite/química , Nanoestruturas/química , Peroxidase/química , Catálise , Peroxidase do Rábano Silvestre/química , Humanos , Peróxido de Hidrogênio/química , Ferro/química , Modelos Moleculares , Nanoestruturas/ultraestrutura , OxirreduçãoRESUMO
Biodegradation of carbon-based nanomaterials has been pursued intensively in the last few years, as one of the most crucial issues for the design of safe, clinically relevant conjugates for biomedical applications. In this paper it is demonstrated that specific functional molecules can enhance the catalytic activity of horseradish peroxidase (HRP) and xanthine oxidase (XO) for the degradation of carbon nanotubes. Two different azido coumarins and one cathecol derivative are linked to multi-walled carbon nanotubes (MWCNTs). These molecules are good reducing substrates and strong redox mediators to enhance the catalytic activity of HRP. XO, known to metabolize various molecules mainly in the mammalian liver, including human, was instead used to test the biodegradability of MWCNTs modified with an azido purine. The products of the biodegradation process are characterized by transmission electron microscopy and Raman spectroscopy. The results indicate that coumarin and catechol moieties have enhanced the biodegradation of MWCNTs compared to oxidized nanotubes, likely due to the capacity of these substrates to better interact with and activate HRP. Although azido purine-MWCNTs are degraded less effectively by XO than oxidized nanotubes, the data uncover the importance of XO in the biodegradation of carbon-nanomaterials leading to their better surface engineering for biomedical applications.
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Peroxidase do Rábano Silvestre/metabolismo , Nanotubos de Carbono/química , Xantina Oxidase/metabolismo , Nanotubos de Carbono/ultraestrutura , Análise Espectral Raman , Propriedades de Superfície , TermogravimetriaRESUMO
Understanding human health risk associated with the rapidly emerging graphene-based nanomaterials represents a great challenge because of the diversity of applications and the wide range of possible ways of exposure to this type of materials. Herein, the biodegradation of graphene oxide (GO) sheets is reported by using myeloperoxidase (hMPO) derived from human neutrophils in the presence of a low concentration of hydrogen peroxide. The degradation capability of the enzyme on three different GO samples containing different degree of oxidation on their graphenic lattice, leading to a variable dispersibility in aqueous media is compared. hMPO fails in degrading the most aggregated GO, but succeeds to completely metabolize highly dispersed GO samples. The spectroscopy and microscopy analyses provide unambiguous evidence for the key roles played by hydrophilicity, negative surface charge, and colloidal stability of the aqueous GO in their biodegradation by hMPO catalysis.
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Grafite/química , Óxidos/química , Peroxidase/metabolismo , Biodegradação Ambiental , Humanos , Tamanho da Partícula , Análise Espectral RamanRESUMO
Novel composite cyclodextrin (CD)-CaCO3 spherical porous microparticles have been synthesized through Ca2+-CD complex formation, which influences the crystal growth of CaCO3. The CDs are entrapped and distributed uniformly in the matrix of CaCO3 microparticles during crystallization. The hydrophobic fluorescent molecules coumarin and Nile red (NR) are efficiently encapsulated into these composite CD-CaCO3 porous particles through supramolecular inclusion complexation between entrapped CDs and hydrophobic molecules. Thermogravimetric (TGA) and infrared spectroscopy (IR) analysis of composite CD-CaCO3 particles reveals the presence of large CDs and their strong interaction with calcium carbonate nanoparticles. The resulting composite CD-CaCO3 microparticles are utilized as sacrificial templates for preparation of CD-modified layer-by-layer (LbL) capsules. After dissolution of the carbonate core, CDs are retained in the interior of the capsules in a network fashion and assist in the encapsulation of hydrophobic molecules. The efficient encapsulation of the hydrophobic fluorescent dye, coumarin, was successfully demonstrated using CD-modified capsules. In vitro release of the encapsulated coumarin from the CD-CaCO3 and CD-modified capsules has been demonstrated.
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A novel and simple route for near-infrared (NIR)-light controlled release of drugs has been demonstrated using graphene oxide (GO) composite microcapsules based on the unique optical properties of GO. Upon NIR-laser irradiation, the microcapsules were ruptured in a point-wise fashion due to local heating which in turn triggers the light-controlled release of the encapsulated anticancer drug doxorubicin (Dox) from these capsules.
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Cápsulas/efeitos da radiação , Doxorrubicina/administração & dosagem , Grafite/efeitos da radiação , Raios Infravermelhos , Portadores de Fármacos , Sistemas de Liberação de MedicamentosRESUMO
Novel composite graphene oxide (GO)/poly(allylamine hydrochloride) (PAH) multilayer capsules have been fabricated by layer-by-layer (LbL) assembly. They were found to possess unique permeability properties compared to traditional LbL capsules. These hybrid capsules showed special "core-shell" loading property for encapsulation of dual drugs simultaneously into the core and shell of the capsules respectively.