Hysteresis-Free, Elastic, and Tough Hydrogel with Stretch-Rate Independence and High Stability in Physiological Conditions.

Many existing synthetic hydrogels are inappropriate for repetitive motions because of large hysteresis, and their mechanical properties in warm and saline physiological conditions remain understudied. In this study, a stretch-rate-independent, hysteresis-free, elastic, and tough nanocomposite hydrogel that can maintain its mechanical properties in phosphate-buffered saline of 37 °C similar to warm and saline conditions of the human body is developed. The strength, stiffness, and toughness of the hydrogel are simultaneously reinforced by biomimetic silica nanoparticles with a surface of embedded circular polyamine chains. Such distinctive surfaces form robust interfacial interactions by local topological folding/entanglement with the polymer chains of the matrix. Load transfer from the soft polymer matrix to stiff nanoparticles, along with the elastic sliding/unfolding/disentanglement of polymer chains, overcomes the traditional trade-off between strength/stiffness and toughness and allows for hysteresis-free, strain-rate-independent, and elastic behavior. This robust reinforcement is sustained in warm phosphate-buffered saline. These properties demonstrate the application potential of the developed hydrogel as a soft, elastic, and tough bio-strain sensor that can detect dynamic motions across various deformation speeds and ranges. The findings provide a simple yet effective approach to developing practical hydrogels with a desirable combination of strength/stiffness and toughness, in a fully swollen and equilibrated state.

Tilapia-Derived Granular Hydrogel as a 3D Scaffold Promoting Rapid Wound Healing.

The skin, a crucial organ that protects the body, is vulnerable to external damage. Traditional tissue regeneration methods, including bulk hydrogels, aim to facilitate wound healing by interacting with host cells and providing a conducive environment. However, the nanoscale porosity of conventional hydrogels limits cell penetration and tissue regeneration. To overcome this, hydrogels composed of microgels have emerged as promising alternatives. In this study, we propose a granular hydrogel using decellularized tilapia skin. The tilapia skin-based microgels are cost-effective, immune-friendly, and have a high collagen content. Microgels based on the decellularized extracellular matrix of tilapia were successfully fabricated by using microfluidics. Through the assembly of these microgels using adhesive hyaluronic acid-catechol, the resulting 3D granular hydrogel scaffold facilitated enhanced cell growth, accelerated cell differentiation, and successful healing of full-thickness wounds in a mouse model. This study reveals the potential of tilapia skin-based granular hydrogel assembly in wound healing, overcoming conventional hydrogel limits.

Polydopamine-Coated Silk Fiber with Controllable Length for Enhanced Hemostatic Application.

The development of highly effective hemostatic materials with high biocompatibility and outstanding performance is vital to the field of biomaterials. In this study, we develop a hemostatic fiber material that exhibits high biocompatibility and excellent performance. By incorporating polydopamine (PDA) into the alkaline treatment of silk fibroin (SF), we achieve PDA-coated SF fibers with lengths that can be controlled by the alkaline concentration. The PDA coating significantly enhances the hemostatic ability of the silk fibers and exhibits superior performance in both in vitro and ex vivo experiments. By performing animal studies involving a mouse liver puncture model and a femoral vein incision model, we demonstrate the remarkable hemostatic capability of the PDA-coated SF fibers, as evidenced by the lower blood loss compared to that of a commercial hemostat powder. These findings highlight the potential of applying a PDA-assisted alkaline treatment to SF fibers to efficiently create hemostatic fibers with controllable lengths, which would be promising candidates for clinical hemostatic applications.

Therapeutic Hydrogel Patch to Treat Atopic Dermatitis by Regulating Oxidative Stress.

Atopic dermatitis (AD) is a chronic inflammatory disease associated with unbalanced immune responses in skin tissue. Although steroid drugs and antihistamines are generally used to treat AD, continuous administration causes multiple side effects. High oxidative stress derived from reactive oxygen species (ROS) has been implicated in the pathogenesis of AD. A high level of ROS promotes the release of pro-inflammatory cytokines and T-cell differentiation, resulting in the onset and deterioration of AD. Here, we report a therapeutic hydrogel patch suppressing the high oxidative stress generated in AD lesions. The hydrogel embedded with ROS-scavenging ceria nanoparticles leads to the decrease of both extracellular and intracellular ROS and exhibits cytoprotective effects in a highly oxidative condition. AD-induced mouse model studies show enhanced therapeutic outcomes, including a decrease in the epidermal thickness and levels of AD-associated immunological biomarkers. These findings indicate that a ROS-scavenging hydrogel could be a promising therapeutic hydrogel patch for treating and managing AD.

Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.

Developing an Individual Glucose Prediction Model Using Recurrent Neural Network.

In this study, we propose a personalized glucose prediction model using deep learning for hospitalized patients who experience Type-2 diabetes. We aim for our model to assist the medical personnel who check the blood glucose and control the amount of insulin doses. Herein, we employed a deep learning algorithm, especially a recurrent neural network (RNN), that consists of a sequence processing layer and a classification layer for the glucose prediction. We tested a simple RNN, gated recurrent unit (GRU), and long-short term memory (LSTM) and varied the architectures to determine the one with the best performance. For that, we collected data for a week using a continuous glucose monitoring device. Type-2 inpatients are usually experiencing bad health conditions and have a high variability of glucose level. However, there are few studies on the Type-2 glucose prediction model while many studies performed on Type-1 glucose prediction. This work has a contribution in that the proposed model exhibits a comparative performance to previous works on Type-1 patients. For 20 in-hospital patients, we achieved an average root mean squared error (RMSE) of 21.5 and an Mean absolute percentage error (MAPE) of 11.1%. The GRU with a single RNN layer and two dense layers was found to be sufficient to predict the glucose level. Moreover, to build a personalized model, at most, 50% of data are required for training.

A facile approach to enhance antigen response for personalized cancer vaccination.

Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhance antigen immunogenicity. The MSR-PEI vaccine significantly enhanced host dendritic cell activation and T-cell response over the existing MSR vaccine and bolus vaccine formulations. Impressively, a single injection of the MSR-PEI vaccine using an E7 peptide completely eradicated large, established TC-1 tumours in about 80% of mice and generated immunological memory. When immunized with a pool of B16F10 or CT26 neoantigens, the MSR-PEI vaccine eradicated established lung metastases, controlled tumour growth and synergized with anti-CTLA4 therapy. Our findings from three independent tumour models suggest that the MSR-PEI vaccine approach may serve as a facile and powerful multi-antigen platform to enable robust personalized cancer vaccination.

Direct Chemical Synthesis of Plasmonic Black Colloidal Gold Superparticles with Broadband Absorption Properties.

Self-assembly of plasmonic metal nanoparticles can provide an opportunity of creating colloidal superparticles with fascinating optical properties arising from interparticle plasmonic coupling, but typically requires multiple steps involving solvent and/or ligand exchange. We developed a direct, one-step chemical synthesis of plasmonic black colloidal Au superparticles with broadband absorption in visible and near-infrared regions. During the synthesis, the Au superparticles were formed through self-assembly of in-situ-formed Au nanoparticles driven by solvophobic interactions between nanoparticles and solvent. These superparticles could be solution-processed to fabricate a thin film, which exhibited near-perfect absorption over a broad range from 400 nm to 2.5 µm as well as the excellent antireflective property. Thanks to their broadband absorption property, the Au superparticles showed good performances for near-infrared surface-enhanced Raman spectroscopy and light-to-heat conversion.

Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage.

Background and Purpose- Despite early aneurysm repair and aggressive management for complications, subarachnoid hemorrhage (SAH) results in at least 25% mortality rate and 50% persistent neurological deficit. We investigated whether ceria nanoparticles which have potent antioxidative activities can protect against subarachnoid hemorrhage via attenuating fatal brain injuries. Methods- Uniform, 3 nm, water-dispersed ceria nanoparticles were prepared from short sol-gel reaction of cerium (III) ions with aminocaproic acid in aqueous phase. SAH was induced by endovascular perforation of middle cerebral artery of rats. A single dose of ceria nanoparticles (0.5 mg Ce/kg) or saline control was randomly administered intravenously at an hour post-SAH. Neuronal death, macrophage infiltration, SAH grade, and brain edema were evaluated at 72 hours. Mortality and neurological function were assessed for 14 days. Results- The obtained ceria nanoparticles with high Ce3+ to Ce4+ ratio demonstrated potent antioxidative, cytoprotective, and anti-inflammatory activities in vitro. In rodent SAH models, the severity of hemorrhage was comparable between the ceria nanoparticles- and saline-treated groups. However, ceria nanoparticles significantly reduced neuronal death, macrophage infiltration, and brain edema after SAH. Ceria nanoparticles successfully improved survival rates (88.2% in the ceria nanoparticles group versus 21.1% in the control group; P<0.001) and neurological outcomes (modified Garcia score: 12.1±0.5 in the ceria nanoparticles group versus 4.4±0.5 in the control group; P<0.001) of the animals with SAH. Conclusions- Ceria nanoparticles, totally synthesized in aqueous phase using aminocaproic acid, demonstrated promising results against SAH via potent antioxidative, neuroprotective and anti-inflammatory activities. Given the obvious limitations of current therapies for SAH, ceria nanoparticles can be a potential therapeutic agent which might result in a paradigm shift in SAH treatment.

A Hydrogel-Film Casting to Fabricate Platelet-Reinforced Polymer Composite Films Exhibiting Superior Mechanical Properties.

The fabrication of mechanically superior polymer composite films with controllable shapes on various scales is difficult. Despite recent research on polymer composites consisting of organic matrices and inorganic materials with layered structures, these films suffer from complex preparations and limited mechanical properties that do not have even integration of high strength, stiffness, and toughness. Herein, a hydrogel-film casting approach to achieve fabrication of simultaneously strong, stiff, and tough polymer composite films with well-defined microstructure, inspired from a layer-by-layer structure of nacre is reported. Ca2+ -crosslinked alginate hydrogels incorporated with platelet-like alumina particles are dried to form composite films composed of horizontally aligned alumina platelets and alginate matrix with uniformly layered microstructure. Alumina platelets are evenly distributed parallel without precipitations and contribute to synergistic enhancements of strength, stiffness and toughness in the resultant film. Consequentially, Ca2+ -crosslinked alginate/alumina (Ca2+ -Alg/Alu) films show exceptional tensile strength (267 MPa), modulus (17.9 GPa), and toughness (3.60 MJ m-3 ). Furthermore, the hydrogel-film casting allows facile preparation of polymer composite films with controllable shapes and various scales. The results suggest an alternative approach to design and prepare polymer composites with the layer-by-layer structure for superior mechanical properties.

Extra-Large Pore Mesoporous Silica Nanoparticles for Directing in Vivo M2 Macrophage Polarization by Delivering IL-4.

Over the past decade, mesoporous silica nanoparticles (MSNs) smaller than 200 nm with a high colloidal stability have been extensively studied for systemic drug delivery. Although small molecule delivery via MSNs has been successful, the encapsulation of large therapeutic biomolecules, such as proteins or DNA, is limited due to small pore size of the conventional MSNs obtained by soft-templating. Here, we report the synthesis of mesoporous silica nanoparticles with extra-large pores (XL-MSNs) and their application to in vivo cytokine delivery for macrophage polarization. Uniform, size-controllable XL-MSNs with 30 nm extra-large pores were synthesized using organic additives and inorganic seed nanoparticles. XL-MSNs showed significantly higher loadings for the model proteins with different molecular weights compared to conventional small pore MSNs. XL-MSNs were used to deliver IL-4, which is an M2-polarizing cytokine and very quickly degraded in vivo, to macrophages and polarize them to anti-inflammatory M2 macrophages in vivo. XL-MSNs induced a low level of reactive oxygen species (ROS) production and no pro-inflammatory cytokines in bone marrow-derived macrophages (BMDMs) and in mice injected intravenously with XL-MSNs. We found that the injected XL-MSNs were targeted to phagocytic myeloid cells, such as neutrophils, monocytes, macrophages, and dendritic cells. Finally, we demonstrated that the injection of IL-4-loaded XL-MSNs successfully triggered M2 macrophage polarization in vivo, suggesting the clinical potential of XL-MSNs for modulating immune systems via targeted delivery of various cytokines.

Bioadhesive Nanoaggregates Based on Polyaspartamide-g-C18/DOPA for Wound Healing.

Biocompatible adhesive nanoaggregates were synthesized based on polyaspartamide copolymers grafted with octadecylamine (C18) and 3,4-dihydroxyphenylalanine (DOPA), and their adhesive properties were investigated with regard to wound healing. The chemical structure and morphology of the synthesized polyaspartamide-g-C18/DOPA nanoaggregates were analyzed using 1H-nuclear magnetic resonance spectroscopy (1H NMR), dynamic light scattering (DLS), and transmission electron microscope (TEM). The in vitro adhesive energy was up to 31.04 J m-2 for poly(dimethylacrylamide) gel substrates and 0.1209 MPa for mouse skin, and the in vivo wound breaking strength after 48 h was 1.8291 MPa for C57BL/6 mouse. The MTT assay demonstrated that the synthesized polymeric nanoaggregates were nontoxic. The polyaspartamide-g-C18/DOPA nanoaggregates were in vivo tested to mouse model and demonstrated successful skin adhesion, as the mouse skin was perfectly cured in their dermis within 6 d. As this material has biocompatibility and enough adhesive strength for wound closure, it is expected to be applied as a new type of bioadhesive agent in the human body.

Ultrasound-triggered disruption and self-healing of reversibly cross-linked hydrogels for drug delivery and enhanced chemotherapy.

Biological systems are exquisitely sensitive to the location and timing of physiologic cues and drugs. This spatiotemporal sensitivity presents opportunities for developing new therapeutic approaches. Polymer-based delivery systems are used extensively for attaining localized, sustained release of bioactive molecules. However, these devices typically are designed to achieve a constant rate of release. We hypothesized that it would be possible to create digital drug release, which could be accelerated and then switched back off, on demand, by applying ultrasound to disrupt ionically cross-linked hydrogels. We demonstrated that ultrasound does not permanently damage these materials but enables nearly digital release of small molecules, proteins, and condensed oligonucleotides. Parallel in vitro studies demonstrated that the concept of applying temporally short, high-dose "bursts" of drug exposure could be applied to enhance the toxicity of mitoxantrone toward breast cancer cells. We thus used the hydrogel system in vivo to treat xenograft tumors with mitoxantrone, and found that daily ultrasound-stimulated drug release substantially reduced tumor growth compared with sustained drug release alone. This approach of digital drug release likely will be applicable to a broad variety of polymers and bioactive molecules, and is a potentially useful tool for studying how the timing of factor delivery controls cell fate in vivo.

A Biodegradation Study of SBA-15 Microparticles in Simulated Body Fluid and in Vivo.

Mesoporous silica has received considerable attention as a drug delivery vehicle because of its large surface area and large pore volume for loading drugs and large biomolecules. Recently, mesoporous silica microparticles have shown potential as a three-dimensional vaccine platform for modulating dendritic cells via spontaneous assembly of microparticles in a specific region after subcutaneous injection. For further in vivo applications, the biodegradation behavior of mesoporous silica microparticles must be studied and known. Until now, most biodegradation studies have focused on mesoporous silica nanoparticles (MSNs); here, we report the biodegradation of hexagonally ordered mesoporous silica, SBA-15, with micrometer-sized lengths (∼32 µm with a high aspect ratio). The degradation of SBA-15 microparticles was investigated in simulated body fluid (SBF) and in mice by analyzing the structural change over time. SBA-15 microparticles were found to degrade in SBF and in vivo. The erosion of SBA-15 under biological conditions led to a loss of the hysteresis loop in the nitrogen adsorption/desorption isotherm and fingerprint peaks in small-angle X-ray scattering, specifically indicating a degradation of ordered mesoporous structure. Via comparison to previous results of degradation of MSNs in SBF, SBA-15 microparticles degraded faster than MCM-41 nanoparticles presumably because SBA-15 microparticles have a pore size (∼8 nm) and a pore volume larger than those of MCM-41 mesoporous silica. The surface functional groups, the residual amounts of organic templates, and the hydrothermal treatment during the synthesis could affect the rate of degradation of SBA-15. In in vivo testing, previous studies focused on the evaluation of toxicity of mesoporous silica particles in various organs. In contrast, we studied the change in the physical properties of SBA-15 microparticles depending on the duration after subcutaneous injection. The pristine SBA-15 microparticles injected into mice subcutaneously slowly degraded over time and lost ordered structure after 3 days. These findings represent the possible in vivo use of microsized mesoporous silica for drug delivery or vaccine platform after local injection.

Ultrastable-Stealth Large Gold Nanoparticles with DNA Directed Biological Functionality.

The stability of gold nanoparticles (AuNPs) in biological samples is very important for their biomedical applications. Although various molecules such as polystyrenesulfonate (PSS), phosphine, DNA, and polyethylene glycol (PEG) have been used to stabilize AuNPs, it is still very difficult to stabilize large AuNPs. As a result, biomedical applications of large (30-100 nm) AuNPs are limited, even though they possess more favorable optical properties and are easier to be taken up by cells than smaller AuNPs. To overcome this limitation, we herein report a novel method of preparing large (30-100 nm) AuNPs with a high colloidal stability and facile chemical or biological functionality, via surface passivation with an amphiphilic polymer polyvinylpyrrolidone (PVP). This PVP passivation results in an extraordinary colloidal stability for 13, 30, 50, 70, and 100 nm AuNPs to be stabilized in PBS for at least 3 months. More importantly, the PVP capped AuNPs (AuNP-PVP) were also resistant to protein adsorption in the presence of serum containing media and exhibit a negligible cytotoxicity. The AuNP-PVPs functionalized with a DNA aptamer AS1411 remain biologically active, resulting in significant increase in the uptake of the AuNPs (∼12,200 AuNPs per cell) in comparison with AuNPs capped by a control DNA of the same length. The novel method developed in this study to stabilize large AuNPs with high colloidal stability and biological activity will allow much wider applications of these large AuNPs for biomedical applications, such as cellular imaging, molecular diagnosis, and targeted therapy.

Dental Hetero-Graft Materials with Nano Hydroxyapatite Surface Treatment.

We report the development of hydroxyapatite nanoparticle (HAp NP)-functionalized hetero-graft materials (HGMs) for dental applications. These HGMs were prepared by attaching platelet-, needle-, and sphere-shaped HAp NPs to the surface of xenograft materials through chemical conjugation. Although all three HAp NPs contributed to increase the surface area of bone graft material (BGM), the shape of the HAp NPs was a determining factor. Platelet HAp NPs were most effective, because they caused a 48.9% increase in BGM surface area whereas the influence of the spherical NP was only a 6.7% increase. This suggests that geometric factors regarding both the attached HAp NPs and graft material surface are essential in controlling the surface roughness of graft materials. Among the three HAp NPs, it was the platelet HAp NPs that helped to increase the efficacy of the BGM most significantly. Compared with BGM with no HAp NP attachment, HGM with platelet HAp NP ('platelet-HGM) treatment had ~46.1% higher cell attachment and proliferation rate. The MTT assay also showed that the HAp NP-treated hetero-graft materials had negligible cytotoxicity.

Cell-friendly inverse opal-like hydrogels for a spatially separated co-culture system.

Three-dimensional macroporous scaffolds have extensively been studied for cell-based tissue engineering but their use is mostly limited to mechanical support for cell adhesion and growth on the surface of macropores. Here, a templated fabrication method is described to prepare cell-friendly inverse opal-like hydrogels (IOHs) allowing both cell encapsulation within the hydrogel matrix and cell seeding on the surface of macropores. Ionically crosslinked alginate microbeads and photocrosslinkable biocompatible polymers are used as a sacrificial template and as a matrix, respectively. The alginate microbeads are easily removed by a chelating agent, with minimal toxicity for the encapsulated cells during template removal. The outer surface of macropores in IOHs can also provide a space for cell adherence. The cells encapsulated or attached in IOHs are able to remain viable and to proliferate over time. The elastic modulus and cell-adhesion properties of IOHs can be easily controlled and tuned. Finally, it is demonstrated that IOH can be used to co-culture two distinct cell populations in different spatial positions. This cell-friendly IOH system provides a 3D scaffold for organizing different cell types in a controllable microenvironment to investigate biological processes such as stem cell niches or tumor microenvironments.

Active scaffolds for on-demand drug and cell delivery.

Porous biomaterials have been widely used as scaffolds in tissue engineering and cell-based therapies. The release of biological agents from conventional porous scaffolds is typically governed by molecular diffusion, material degradation, and cell migration, which do not allow for dynamic external regulation. We present a new active porous scaffold that can be remotely controlled by a magnetic field to deliver various biological agents on demand. The active porous scaffold, in the form of a macroporous ferrogel, gives a large deformation and volume change of over 70% under a moderate magnetic field. The deformation and volume variation allows a new mechanism to trigger and enhance the release of various drugs including mitoxantrone, plasmid DNA, and a chemokine from the scaffold. The porous scaffold can also act as a depot of various cells, whose release can be controlled by external magnetic fields.

Lignin-Based Antioxidant Hydrogel Patch for the Management of Atopic Dermatitis by Mitigating Oxidative Stress in the Skin.

Atopic dermatitis (AD), a chronic skin condition characterized by itching, redness, and inflammation, is closely associated with heightened levels of endogenous reactive oxygen species (ROS) in the skin. ROS can contribute to the onset and progression of AD through oxidative stress, which leads to the release of proinflammatory cytokines, T-cell differentiation, and the exacerbation of skin symptoms. In this study, we aim to develop a therapeutic antioxidant hydrogel patch for the potential treatment of AD using lignin, a biomass waste material. Lignin contains polyphenol groups that enable it to scavenge ROS and exhibit antioxidant properties. The lignin hydrogel patches, possessing optimized mechanical properties through the control of the lignin and cross-linker ratio, demonstrated high ROS-scavenging capabilities. Furthermore, the lignin hydrogel demonstrated excellent biocompatibility with the skin, exhibiting beneficial properties in protecting human keratinocytes under high oxidative conditions. When applied to an AD mouse model, the hydrogel patch effectively reduced epidermal thickness in inflamed regions, decreased mast cell infiltration, and regulated inflammatory cytokine levels. These findings collectively suggest that lignin serves as a therapeutic hydrogel patch for managing AD by modulating oxidative stress through its ROS-scavenging ability.

Administration of ROS-Scavenging Cerium Oxide Nanoparticles Simply Mixed with Autoantigenic Peptides Induce Antigen-Specific Immune Tolerance against Autoimmune Encephalomyelitis.

The scavenging ability of cerium oxide nanoparticles (CeNPs) for reactive oxygen species has been intensively studied in the field of catalysis. However, the immunological impact of these particles has not yet been thoroughly investigated, despite intensive research indicating that modulation of the reactive oxygen species could potentially regulate cell fate and adaptive immune responses. In this study, we examined the intrinsic capability of CeNPs to induce tolerogenic dendritic cells via their reactive oxygen species-scavenging effect when the autoantigenic peptides were simply mixed with CeNPs. CeNPs effectively reduced the intracellular reactive oxygen species levels in dendritic cells in vitro, leading to the suppression of costimulatory molecules as well as NLRP3 inflammasome activation, even in the presence of pro-inflammatory stimuli. Subcutaneously administrated PEGylated CeNPs were predominantly taken up by antigen-presenting cells in lymph nodes and to suppress cell maturation in vivo. The administration of a mixture of PEGylated CeNPs and myelin oligodendrocyte glycoprotein peptides, a well-identified autoantigen associated with antimyelin autoimmunity, resulted in the generation of antigen-specific Foxp3+ regulatory T cells in mouse spleens. The induced peripheral regulatory T cells actively inhibited the infiltration of autoreactive T cells and antigen-presenting cells into the central nervous system, ultimately protecting animals from experimental autoimmune encephalomyelitis when tested using a mouse model mimicking human multiple sclerosis. Overall, our findings reveal the potential of CeNPs for generating antigen-specific immune tolerance to prevent multiple sclerosis, opening an avenue to restore immune tolerance against specific antigens by simply mixing the well-identified autoantigens with the immunosuppressive CeNPs.