Interaction of vascular endothelial cells with hydrophilic fullerene nanoarchitectured structures in 2D and 3D environments.

The interaction between diverse nanoarchitectured fullerenes and cells is crucial for biomedical applications. Here, we detailed the preparation of hydrophilic self-assembled fullerenes by the liquid-liquid interfacial precipitation (LLIP) method and hydrophilic coating of the materials as a possible vascularization strategy. The interactions of vascular endothelial cells (ECs) with hydrophilic fullerene nanotubes (FNT-P) and hydrophilic fullerene nanowhiskers (FNW-P) were investigated. The average length and diameter of FNT-P were 16 ± 2 µm and 3.4 ± 0.4 µm (i.e. aspect ratios of 4.6), respectively. The average length and diameter of FNW-P were 65 ± 8 µm and 1.2 ± 0.2 µm (i.e. aspect ratios of 53.9), respectively. For two-dimensional (2D) culture after 7 days, the ECs remained viable and proliferated up to ~ 420% and ~ 400% with FNT-P and FNW-P of 50 µg/mL, respectively. Furthermore, an optimized chitosan-based self-healing hydrogel with a modulus of ~400 Pa was developed and used to incorporate self-assembled fullerenes as in vitro three-dimensional (3D) platforms to investigate the impact of FNT-P and FNW-P on ECs within a 3D environment. The addition of FNW-P or FNT-P (50 µg/mL) in the hydrogel system led to proliferation rates of ECs up to ~323% and ~280%, respectively, after 7 days of culture. The ECs in FNW-P hydrogel displayed an elongated shape with aligned morphology, while those in FNT-P hydrogel exhibited a rounded and clustered distribution. Vascular-related gene expressions of ECs were significantly upregulated through interactions with these fullerenes. Thus, the combined use of different nanoarchitectured self-assembled fullerenes and self-healing hydrogels may offer environmental cues influencing EC development in a 3D biomimetic microenvironment, holding promise for advancing vascularization strategy in tissue engineering.

Self-assembled fullerenes with large aspect ratios modulate the morphology and gene expression of endothelial cells within a soft biomimetic 3D microenvironment, representing a promising new vascularization strategy in tissue engineering.

Self-healing hydrogel as an injectable implant: translation in brain diseases.

Tissue engineering biomaterials are aimed to mimic natural tissue and promote new tissue formation for the treatment of impaired or diseased tissues. Highly porous biomaterial scaffolds are often used to carry cells or drugs to regenerate tissue-like structures. Meanwhile, self-healing hydrogel as a category of smart soft hydrogel with the ability to automatically repair its own structure after damage has been developed for various applications through designs of dynamic crosslinking networks. Due to flexibility, biocompatibility, and ease of functionalization, self-healing hydrogel has great potential in regenerative medicine, especially in restoring the structure and function of impaired neural tissue. Recent researchers have developed self-healing hydrogel as drug/cell carriers or tissue support matrices for targeted injection via minimally invasive surgery, which has become a promising strategy in treating brain diseases. In this review, the development history of self-healing hydrogel for biomedical applications and the design strategies according to different crosslinking (gel formation) mechanisms are summarized. The current therapeutic progress of self-healing hydrogels for brain diseases is described as well, with an emphasis on the potential therapeutic applications validated by in vivo experiments. The most recent aspect as well as the design rationale of self-healing hydrogel for different brain diseases is also addressed.

Enhancement of Cell Behavior by the Polysaccharide Extract of Arthrospira and Potential Biomedical Applications.

Arthrospira is one of the most studied cyanobacteria and has been reported with practical applications. Among the substances derived from Arthrospira, polysaccharides have received relatively less attention than phycocyanins, though they have more abundant structural variations and specific properties. Herein, a new Arthrospira-derived sulfated polysaccharide was explored for its potential bioactive functions. The ability of this sulfated polysaccharide to promote the behavior of neural stem cells (NSCs) in three-dimensional hydrogel was examined for the first time. NSCs encapsulated in the sulfated polysaccharide-containing hydrogel showed better proliferation than the control hydrogel as well as a unique cell clustering behavior, i.e., formation of multicellular spherical clusters (40-60 µm). The sulfated polysaccharide, in an appropriate range of concentration (5 mg/mL), also maintained the stemness of NSCs in hydrogel and facilitated their differentiation. In addition, the potentials of the new sulfated polysaccharide as a coating material and as a component for drug carrier were verified. The sulfated polysaccharide-modified substrate exhibited superhydrophilicity (contact angle ~9°) and promoted cell adhesion to the substrate. Composite nanoparticles composed of the sulfated polysaccharide and other differently charged polysaccharides were produced with an average diameter of ~240 nm and estimated drug loading of ~18%. The new Arthrospira-derived sulfated polysaccharide is a promising candidate for cell culture, surface-modification, and drug-delivery applications in the biomedical field.

Antiviral and Antibacterial Sulfated Polysaccharide-Chitosan Nanocomposite Particles as a Drug Carrier.

Drug delivery system (DDS) refers to the method of delivering drugs to the targeted sites with minimal risk. One popular strategy of DDS is using nanoparticles as a drug carrier, which are made from biocompatible and degradable polymers. Here, nanoparticles composed of Arthrospira-derived sulfated polysaccharide (AP) and chitosan were developed and expected to possess the capabilities of antiviral, antibacterial, and pH-sensitive properties. The composite nanoparticles, abbreviated as APC, were optimized for stability of morphology and size (~160 nm) in the physiological environment (pH = 7.4). Potent antibacterial (over 2 µg/mL) and antiviral (over 6.596 µg/mL) properties were verified in vitro. The pH-sensitive release behavior and release kinetics of drug-loaded APC nanoparticles were examined for various categories of drugs, including hydrophilic, hydrophobic, and protein drugs, under different pH values of the surroundings. Effects of APC nanoparticles were also evaluated in lung cancer cells and neural stem cells. The use of APC nanoparticles as a drug delivery system maintained the bioactivity of the drug to inhibit the proliferation of lung cancer cells (with ~40% reduction) and to relieve the growth inhibitory effect on neural stem cells. These findings indicate that the pH-sensitive and biocompatible composite nanoparticles of sulfated polysaccharide and chitosan well keep the antiviral and antibacterial properties and may serve as a promising multifunctional drug carrier for further biomedical applications.

Correction: Hung et al. Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells. Int. J. Mol. Sci. 2021, 22, 9262.

The authors wish to make the following correction to this paper [...].

Development of MOF Reinforcement for Structural Stability and Toughness Enhancement of Biodegradable Bioinks.

Three-dimensional (3D) bioprinting is a technology that can precisely fabricate customized tissues and organs. Hydrogel materials that can embed living cells for use in 3D printing are called bioinks. However, there are only limited options of bioinks currently because they require the following features at once, such as printability, repetitive layer-by-layer stacking (stackability), structure stabilization, and biological properties. A polyurethane-gelatin double network hydrogel bioink was previously reported to own tunable modulus through changing the solid content, but cell viability at the high solid content is inevitably reduced. In the present study, the reinforcement effects of a metal-organic framework (MOF), zeolitic imidazolate framework-8 (ZIF-8), in the PUG bioink were evaluated. The printability, stackability, thermoresponsiveness, and shear-thinning behavior of the PUG-ZIF-8 composite hydrogels were examined. It was found that the PUG composite hydrogel containing 1250 µg/mL ZIF-8 crystals showed significant structural stability and modulus enhancement (∼2.5-fold). However, the PUG bioink containing 1250 µg/mL ZIF-8 crystals may lead to cell senescence or death. The cytocompatible concentration of ZIF-8 crystals in the bioink was about 875 µg/mL, and this concentration was much higher than the reported tolerable amount (∼50 µg/mL) of ZIF-8 for biomedical applications. The strong reinforcement effect of ZIF-8 and the drug-loading/sensing possibilities of MOFs may open new opportunities for using MOFs in 3D bioprinting applications.

Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells.

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton's jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.

Engineered Bacteriorhodopsin May Induce Lung Cancer Cell Cycle Arrest and Suppress Their Proliferation and Migration.

Highly expressible bacteriorhodopsin (HEBR) is a light-triggered protein (optogenetic protein) that has seven transmembrane regions with retinal bound as their chromophore to sense light. HEBR has controllable photochemical properties and regulates activity on proton pumping. In this study, we generated HEBR protein and incubated with lung cancer cell lines (A549 and H1299) to evaluate if there was a growth-inhibitory effect with or without light illumination. The data revealed that the HEBR protein suppressed cell proliferation and induced the G0/G1 cell cycle arrest without light illumination. Moreover, the migration abilities of A549 and H1299 cells were reduced by ~17% and ~31% after incubation with HEBR (40 µg/mL) for 4 h. The Snail-1 gene expression level of the A549 cells was significantly downregulated by ~50% after the treatment of HEBR. In addition, HEBR significantly inhibited the gene expression of Sox-2 and Oct-4 in H1299 cells. These results suggested that the HEBR protein may inhibit cell proliferation and cell cycle progression of lung cancer cells, reduce their migration activity, and suppress some stemness-related genes. These findings also suggested the potential of HEBR protein to regulate the growth and migration of tumor cells, which may offer the possibility for an anticancer drug.

Quantitative Bioimage Analysis of Passaging Effect on the Migratory Behavior of Human Mesenchymal Stem Cells During Spheroid Formation.

The quality of stem cells obtained through serial subcultivation is the pivotal factor determining the therapeutic effectiveness of regenerative medicine. However, an effective quality monitoring system for cell culture is yet to be established. Detailed parameter studies of the migratory behavior of stem cells at different passages may provide insight into the deterioration of stemness. Thus, this study aimed to evaluate the feasibility of quantitative bioimage analysis for monitoring stem cell quality during in vitro culture and to explore the passaging effects on stem cell migration. An image-based analytical tool using cell tracking, cytometric analyses, and gating with time-lapse microscopy was developed to characterize the migratory behavior of human mesenchymal stem cells (hMSCs) isolated from human adipose tissue (hADAS) and placenta (hPDMC) cultured on chitosan membranes. Quantitative analysis was performed for the single cells and assembled spheroids selected from 15 videos of Passages 3, 5, and 11 for hADAS and those from 12 videos of Passages 7, 11, and 16 for hPDMC. These passages were selected to represent the young, matured, and degenerated stem cells, respectively. Migratory behavior varied with cell passages. The mobility of single hMSCs decreased at degenerated passages. In addition, enhancement of mobility, due to transformation from single cells to spheroids, occurred at each passage. The young hMSCs seemed more likely to move as single cells rather than as aggregates. Once matured, they tended to aggregate with strong 3D spheroid formability and increased mobility. However, the spheroid formability and mobility decreased at late passage. The increase in aggregation rate with passaging may be a compensatory mechanism to enhance the declining mobility of hMSCs through cell coordination. Our findings regarding the passaging effects on stem-cell migratory behavior agree with biochemical reports, suggesting that the developed imaging method is capable of monitoring the cell-culture quality effectively. © 2020 International Society for Advancement of Cytometry.

Effective naked plasmid DNA delivery into stem cells by microextrusion-based transient-transfection system for in situ cardiac repair.

BACKGROUND AIMS: Combining the use of transfection reagents and physical methods can markedly improve the efficiency of gene delivery; however, such methods often cause cell damage. Additionally, naked plasmids without any vector or physical stimulation are difficult to deliver into stem cells. In this study, we demonstrate a simple and rapid method to simultaneously facilitate efficient in situ naked gene delivery and form a bioactive hydrogel scaffold. METHODS: Transfecting naked GATA binding protein 4 (GATA4) plasmids into human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) by co-extruding naked plasmids and hUC-MSCs with a biomimetic and negatively charged water-based biodegradable thermo-responsive polyurethane (PU) hydrogel through a microextrusion-based transient-transfection system can upregulate the other cardiac marker genes. RESULTS: The PU hydrogels with optimized physicochemical properties (such as hard-soft segment composition, size, hardness and thermal gelation) induced GATA4-transfected hUC-MSCs to express the cardiac marker proteins and then differentiated into cardiomyocyte-like cells in 15 days. We further demonstrated that GATA4-transfected hUC-MSCs in PU hydrogel were capable of in situ revival of heart function in zebrafish in 30 days. CONCLUSIONS: Our results suggest that hUC-MSCs and naked plasmids encapsulated in PU hydrogels might represent a new strategy for in situ tissue therapy using the microextrusion-based transient-transfection system described here. This transfection system is simple, effective and safer than conventional technologies.

Potential of stem cell therapy in intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a common disease associated with high mortality and morbidity. The treatment of patients with ICH includes medical and surgical interventions. New areas of surgical intervention have been focused on the evacuation of hematoma through minimally invasive neurosurgery. In contrast, there have been no significant advances in the development of medical interventions for functional recovery after ICH. Stem cells exert multiple therapeutic functions and have emerged as a promising treatment strategy. Herein, we summarized the pathophysiology of ICH and its treatment targets, and we introduced the therapeutic mechanisms of stem cells (e.g. neutrotrophy and neuroregeneration). Moreover, we reviewed and summarized the experimental designs of the preclinical studies, including the types of cells and the timing and routes of stem cell administration. We further listed and reviewed the completed/published and ongoing clinical trials supporting the safety and efficacy of stem cell therapy in ICH. The limitations of translating preclinical studies into clinical trials and the objectives of future studies were discussed. In conclusion, current literatures showed that stem cell therapy is a promising treatment in ICH and further translation research on judiciously selected group of patients is warranted before it can be extensively applied in clinical practice.

Design Strategies of Conductive Hydrogel for Biomedical Applications.

Conductive hydrogel, with electroconductive properties and high water content in a three-dimensional structure is prepared by incorporating conductive polymers, conductive nanoparticles, or other conductive elements, into hydrogel systems through various strategies. Conductive hydrogel has recently attracted extensive attention in the biomedical field. Using different conductivity strategies, conductive hydrogel can have adjustable physical and biochemical properties that suit different biomedical needs. The conductive hydrogel can serve as a scaffold with high swelling and stimulus responsiveness to support cell growth in vitro and to facilitate wound healing, drug delivery and tissue regeneration in vivo. Conductive hydrogel can also be used to detect biomolecules in the form of biosensors. In this review, we summarize the current design strategies of conductive hydrogel developed for applications in the biomedical field as well as the perspective approach for integration with biofabrication technologies.

Smart polymers for cell therapy and precision medicine.

Soft materials have been developed very rapidly in the biomedical field over the past 10 years because of advances in medical devices, cell therapy, and 3D printing for precision medicine. Smart polymers are one category of soft materials that respond to environmental changes. One typical example is the thermally-responsive polymers, which are widely used as cell carriers and in 3D printing. Self-healing polymers are one type of smart polymers that have the capacity to recover the structure after repeated damages and are often injectable through needles. Shape memory polymers are another type with the ability to memorize their original shape. These smart polymers can be used as cell/drug/protein carriers. Their injectability and shape memory performance allow them to be applied in bioprinting, minimally invasive surgery, and precision medicine. This review will describe the general materials design, characterization, as well as the current progresses and challenges of these smart polymers.

Nanoarchitectonic-Based Material Platforms for Environmental and Bioprocessing Applications.

The challenges of pollution, environmental science, and energy consumption have become global issues of broad societal importance. In order to address these challenges, novel functional systems and advanced materials are needed to achieve high efficiency, low emission, and environmentally friendly performance. A promising approach involves nanostructure-level controls of functional material design through a novel concept, nanoarchitectonics. In this account article, we summarize nanoarchitectonic approaches to create nanoscale platform structures that are potentially useful for environmentally green and bioprocessing applications. The introduced platforms are roughly classified into (i) membrane platforms and (ii) nanostructured platforms. The examples are discussed together with the relevant chemical processes, environmental sensing, bio-related interaction analyses, materials for environmental remediation, non-precious metal catalysts, and facile separation for biomedical uses.

Hydrogels Based on Schiff Base Linkages for Biomedical Applications.

Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff base reversibly reacts even in mild conditions, which allows hydrogels with self-healing ability to recover their structures and functions after damages. Moreover, pH-sensitivity of the Schiff base offers the hydrogels response to biologically relevant stimuli. Different types of Schiff base can provide the hydrogels with tunable mechanical properties and chemical stabilities. In this review, we summarized the design and preparation of hydrogels based on various types of Schiff base linkages, as well as the biomedical applications of hydrogels in drug delivery, tissue regeneration, wound healing, tissue adhesives, bioprinting, and biosensors.

Polyurethane Nanoparticle-Loaded Fenofibrate Exerts Inhibitory Effects on Nonalcoholic Fatty Liver Disease in Mice.

Polyurethane (PU) nanoparticles are potential drug carriers. We aimed to study the in vitro and in vivo efficacy of biodegradable PU nanoparticles loaded with fenofibrate (FNB-PU) on nonalcoholic fatty liver disease (NAFLD). FNB-PU was prepared by a green process, and its preventive effects on NAFLD were investigated on HepG2 cells and mice. FNB-PU showed sustained in vitro FNB release profile. Compared to FNB crude drug, FNB-PU significantly decreased triglyceride content in HepG2 cells incubated with oleic acid and in livers of mice with NAFLD induced by a methionine choline deficient diet, and increased plasma FNB concentration of the mice. FNB-PU increased absorption of FNB and therefore enhanced the inhibitory effects of FNB on NAFLD.

Intervertebral disc needle puncture injury can be repaired using a gelatin-poly (γ-glutamic acid) hydrogel: an in vitro bovine biomechanical validation.

PURPOSE: The subtle impairments of the disc due to anular punctures may have an immediate effect on the functional integrity due to the altered intradiscal pressure, hence the subsequent catabolic degradation. This study evaluates functional restoration of needle puncture injured intervertebral discs with a newly developed injectable hydrogel using the quantitative discomanometry (QD) test. The proposed hydrogel is composed of gelatin and poly (γ-glutamic acid) (γ-PGA) and crosslinked with 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC). METHODS: Thirty-six bovine motion segments were distributed into six groups. Needle puncture injured discs were created in all discs except for those in the first group (intact). The second group included injured discs that received no treatment (injury). The remaining four groups included injured discs repaired with injected hydrogels fabricated with different polymer solutions and EDC concentrations including: gelatin/γ-PGA solution crosslinked with the EDC solution at a 10:1 and 40:1 ratio to form the GP/E(10:1) and GP/E(40:1) groups, respectively, and gelatin and γ-PGA solution crosslinked with the EDC solution at a 10:1 ratio to form the G/E(10:1) or P/E(10:1) groups. The QD tests were performed to evaluate disc integrity of all six groups. RESULTS: Among all hydrogel repair groups, the GP/E(10:1) group was found to have the highest leakage and saturate pressure and was the only group comparable to the intact one. CONCLUSIONS: Restoration of disc integrity secondary to needle puncture injury can be achieved via the repair with the newly developed gelatin hydrogel incorporated with γ-PGA and EDC. These slides can be retrieved under Electronic Supplementary Material.

Functional engineered mesenchymal stem cells with fibronectin-gold composite coated catheters for vascular tissue regeneration.

Vascularization of engineered tissues remains one of the key problems. Here, we described a novel approach to promote vascularization of engineered tissues using fibronectin (FN) incorporated gold nanoparticles (AuNP) coated onto catheters with mesenchymal stem cells (MSCs) for tissue engineering. We found that the FN-AuNP composite with 43.5 ppm of AuNP exhibited better biomechanical properties and thermal stability than pure FN. FN-AuNP composites promoted MSC proliferation and increased the biocompatibility. Mechanistically, vascular endothelial growth factor (VEGF) promoted MSC migration on FN-AuNP through the endothelial oxide synthase (eNOS)/metalloproteinase (MMP) signaling pathway. Vascular femoral artery tissues isolated from the implanted FN-AuNP-coated catheters with MSCs expressed substantial CD31 and alpha-smooth muscle actin (α-SMA), displayed higher antithrombotic activity, as well as better endothelialization ability than those coated with all other materials. These data suggested that the implantation of FN-AuNP-coated catheter with MSCs could be a novel strategy for vascular biomaterials applications.

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals.

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.

Surfactant-modified nanoclay exhibits an antiviral activity with high potency and broad spectrum.

UNLABELLED: Nanomaterials have the characteristics associated with high surface-to-volume ratios and have been explored for their antiviral activity. Despite some success, cytotoxicity has been an issue in nanomaterial-based antiviral strategies. We previously developed a novel method to fully exfoliate montmorillonite clay to generate the most fundamental units of nanoscale silicate platelet (NSP). We further modified NSP by capping with various surfactants and found that the surfactant-modified NSP (NSQ) was less cytotoxic. In this study, we tested the antiviral potentials of a series of natural-clay-derived nanomaterials. Among the derivatives, NSP modified with anionic sodium dodecyl sulfate (NSQc), but not the pristine clay, unmodified NSP, a silver nanoparticle-NSP hybrid, NSP modified with cationic n-octadecanylamine hydrochloride salt, or NSP modified with nonionic Triton X-100, significantly suppressed the plaque-forming ability of Japanese encephalitis virus (JEV) at noncytotoxic concentrations. NSQc also blocked infection with dengue virus (DEN) and influenza A virus. Regarding the antiviral mechanism, NSQc interfered with viral binding through electrostatic interaction, since its antiviral activity can be neutralized by Polybrene, a cationic polymer. Furthermore, NSQc reduced the lethality of JEV and DEN infection in mouse challenge models. Thus, the surfactant-modified exfoliated nanoclay NSQc may be a novel nanomaterial with broad and potent antiviral activity. IMPORTANCE: Nanomaterials have being investigated as antimicrobial agents, yet their antiviral potential is overshadowed by their cytotoxicity. By using a novel method, we fully exfoliated montmorillonite clay to generate the most fundamental units of nanoscale silicate platelet (NSP). Here, we show that the surfactant-modified NSP (NSQ) is less cytotoxic and that NSQc (NSP modified with sodium dodecyl sulfate) could potently block infection by dengue virus (DEN), Japanese encephalitis virus (JEV), and influenza A virus at noncytotoxic concentrations. For the antiviral mechanism, we find that the electrostatic interaction between the negatively charged NSQc and the positively charged virus particles blocks viral binding. Furthermore, we used mouse challenge models of JEV and DEN to demonstrate the in vivo antiviral potential of NSQc. Thus, NSQc may function as a potent and safe antiviral nanohybrid against several viruses, and our success in synthesizing surfactant-modified NSP with antiviral activity may shed some light on future antiviral development.