Mesoporous polydopamine nanoparticle-based tolerogenic vaccine induces antigen-specific immune tolerance to prevent and treat autoimmune multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disorder derived from autoreactive immune system attacking the protective myelin sheath that surrounds nerves in the central nervous system (CNS). Here, a tolerogenic nanovaccine for generating an antigen-specific immune tolerance for treating MS is proposed. It consisted of a mesoporous polydopamine (mPDA) nanoparticle, characterized by high reactive oxygen species (ROS)-scavenging property, loaded with MS-derived autoantigen.

HO Self-Supplying CaO Nanoplatform Induces Ca Overload Combined with Chemodynamic Therapy to Enhance Cancer Immunotherapy.

Integrating chemodynamic therapy (CDT) with Ca overload offers a potent strategy for enhancing cancer immunotherapy. However, the effectiveness of this approach is significantly constrained by the scarce availability of HO in solid tumors. Here, we engineered a nanoplatform based on CaO nanoparticles (NPs) capable of encapsulating curcumin (CUR) and self-supplying HO for synergistic CDT-augmented antitumor immunotherapy (CaO@CUR@ZIF-Cu, denoted as CCZC).

High Cellular Internalization of Virus-Like Mesoporous Silica Nanoparticles Enhances Adaptive Antigen-Specific Immune Responses against Cancer.

Effective activation of an antigen-specific immune response hinges upon the intracellular delivery of cancer antigens to antigen-presenting cells (APCs), marking the initial stride in cancer vaccine development. Leveraging biomimetic topological morphology, we employed virus-like mesoporous silica nanoparticles (VMSNs) coloaded with antigens and toll-like receptor 9 (TLR9) agonists to craft a potent cancer vaccine. Our VMSNs could be efficiently internalized by APCs to a greater extent than their nonviral structured counterparts, thereby promoting the activation of APCs by upregulating the TLR9 pathway and cross-presenting ovalbumin (OVA) epitopes.

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.

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.

ROS-Scavenging Lignin-Based Tolerogenic Nanoparticle Vaccine for Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating autoimmune disease, in which the immune system attacks myelin. Although systemic immunosuppressive agents have been used to treat MS, long-term treatment with these drugs causes undesirable side effects such as altered glucose metabolism, insomnia, and hypertension. Herein, we propose a tolerogenic therapeutic vaccine to treat MS based on lignin nanoparticles (LNP) with intrinsic reactive oxygen species (ROS)-scavenging capacity derived from their phenolic moieties.

pH-temperature Responsive Hydrogel-Mediated Delivery of Exendin-4 Encapsulated Chitosan Nanospheres for Sustained Therapeutic Efficacy in Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2D) is a chronic, obesity-related, and inflammatory disorder characterize by insulin resistance, inadequate insulin secretion, hyperglycemia, and excessive glucagon secretion. Exendin-4 (EX), a clinically established antidiabetic medication that acts as a glucagon-like peptide-1 receptor agonist, is effective in lowering glucose levels and stimulating insulin secretion while significantly reducing hunger. However, the requirement for multiple daily injections due to EX's short half-life is a significant limitation in its clinical application, leading to high treatment costs and patient inconvenience.

Immunosuppressive biomaterial-based therapeutic vaccine to treat multiple sclerosis via re-establishing immune tolerance.

Current therapies for autoimmune diseases, such as multiple sclerosis (MS), induce broad suppression of the immune system, potentially promoting opportunistic infections. Here, we report an immunosuppressive biomaterial-based therapeutic vaccine carrying self-antigen and tolerance-inducing inorganic nanoparticles to treat experimental autoimmune encephalomyelitis (EAE), a mouse model mimicking human MS. Immunization with self-antigen-loaded mesoporous nanoparticles generates Foxp3 regulatory T-cells in spleen and systemic immune tolerance in EAE mice, reducing central nervous system-infiltrating antigen-presenting cells (APCs) and autoreactive CD4 T-cells.

Superstrong, superstiff, and conductive alginate hydrogels.

For the practical use of synthetic hydrogels as artificial biological tissues, flexible electronics, and conductive membranes, achieving requirements for specific mechanical properties is one of the most prominent issues. Here, we demonstrate superstrong, superstiff, and conductive alginate hydrogels with densely interconnecting networks implemented via simple reconstructing processes, consisting of anisotropic densification of pre-gel and a subsequent ionic crosslinking with rehydration. The reconstructed hydrogel exhibits broad ranges of exceptional tensile strengths (8-57 MPa) and elastic moduli (94-1,290 MPa) depending on crosslinking ions.

Injectable Hydrogel Based on Protein-Polyester Microporous Network as an Implantable Niche for Active Cell Recruitment.

Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed an injectable protein-polymer-based porous hydrogel network composed of lysozyme and poly(ε-caprolactone-co-lactide)--poly(ethylene glycol)--poly(ε-caprolactone-co-lactide (PCLA) (Lys-PCLA) bioconjugate for the active recruitment dendritic cells (DCs).

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.

Nanozyme-Based Enhanced Cancer Immunotherapy.

Catalytic nanoparticles with natural enzyme-mimicking properties, known as nanozymes, have emerged as excellent candidate materials for cancer immunotherapy. Owing to their enzymatic activities, artificial nanozymes not only serve as responsive carriers to load drugs and therapeutic molecules for cancer treatment, but also act as enzymes for modulating the immunosuppression of the tumor microenvironment (TME) via the catalytic activities of catalase, peroxidase, superoxide dismutase, and oxidase. The immunosuppressive pro-tumor TME can be reversed to the immunoactive anti-tumor TME by utilizing both reactive oxygen species (ROS)-generating and ROS-scavenging nanozymes, which enhance the efficacy of cancer immunotherapy.

Enhanced Cancer DNA Vaccine Direct Transfection to Host Dendritic Cells Recruited in Injectable Scaffolds.

Deoxyribonucleic acid (DNA) vaccines are a promising cancer immunotherapy approach. However, effective delivery of DNA to antigen-presenting cells (..

Hollow Mesoporous Silica Nanoparticles with Extra-Large Mesopores for Enhanced Cancer Vaccine.

Owing to the limitations of conventional cancer therapies, cancer immunotherapy has emerged for the prevention of cancer recurrence. To provoke adaptive immune responses that are antigen-specific, it is important to develop an efficient antigen delivery system that can enhance the activation and maturation of the dendritic cells (DCs) in the human body. In this study, we synthesize hollow mesoporous silica nanoparticles with extra-large mesopores (H-XL-MSNs) based on a single-step synthesis from core-shell mesoporous silica nanoparticles with a core composed of an assembly of iron oxide nanoparticles.

Injectable dual-scale mesoporous silica cancer vaccine enabling efficient delivery of antigen/adjuvant-loaded nanoparticles to dendritic cells recruited in local macroporous scaffold.

Despite the potential of nanoparticle-based vaccines, their therapeutic efficacy for cancer immunotherapy is limited. To elicit robust antigen-specific adaptive immune responses, antigen-loaded nanoparticles are employed for transport into host dendritic cells (DCs); however, only a minority of the nanoparticles can be engulfed by host DCs. Herein, an injectable dual-scale mesoporous silica vaccine consisting of mesoporous silica microrods (MSRs) coupled with mesoporous silica nanoparticles (MSNs) is introduced.

Degradation-regulated architecture of injectable smart hydrogels enhances humoral immune response and potentiates antitumor activity in human lung carcinoma.

Cancer vaccines that elicit a robust and durable antitumor response show great promise in cancer immunotherapy. Nevertheless, low immunogenicity and weak immune response limit the application of cancer vaccines. To experience next generation cancer vaccines that elicit robust, durable, and anti-tumor T cell response, herein we design injectable smart hydrogels (ISHs) that self-assemble into a cellular microenvironment-like microporous network using a simple hypodermic needle injection, to localize the immune cells and program host cells.

Physically crosslinked injectable hydrogels for long-term delivery of oncolytic adenoviruses for cancer treatment.

A dual pH- and temperature-responsive physically crosslinked and injectable hydrogel system was developed for efficient and long-term delivery of oncolytic adenoviruses (Ads). Three different types of physically crosslinked hydrogels with different chemical compositions and properties were prepared. These hydrogels with good biocompatibility can be injected at pH 9.

A 3D Macroporous Alginate Graphene Scaffold with an Extremely Slow Release of a Loaded Cargo for In Situ Long-Term Activation of Dendritic Cells.

Ex vivo manipulation of autologous antigen-presenting cells and their subsequent infusion back into the patient to dictate immune response is one of the promising strategies in cancer immunotherapy. Here, a 3D alginate scaffold embedded with reduced graphene oxide (rGO) is proposed as a vaccine delivery platform for in situ long-term activation of antigen-presenting dendritic cells (DCs). High surface area and hydrophobic surface of the rGO component of the scaffold provide high loading and a very slow release of a loaded antigen, danger signal, and/or chemoattractant from the scaffold.

Modularly engineered injectable hybrid hydrogels based on protein-polymer network as potent immunologic adjuvant in vivo.

Lymphoid organs, which are populated by dendritic cells (DCs), are highly specialized tissues and provide an ideal microenvironment for T-cell priming. However, intramuscular or subcutaneous delivery of vaccine to DCs, a subset of antigen-presenting cells, has failed to stimulate optimal immune response for effective vaccination and need for adjuvants to induce immune response. To address this issue, we developed an in situ-forming injectable hybrid hydrogel that spontaneously assemble into microporous network upon subcutaneous administration, which provide a cellular niche to host immune cells, including DCs.

Mesoporous Silica as a Versatile Platform for Cancer Immunotherapy.

Immunotherapy has been recognized for decades as a promising therapeutic method for cancer treatment. To enhance host immune responses against cancer, antigen-presenting cells (APCs; e.g.

Smart vaccine delivery based on microneedle arrays decorated with ultra-pH-responsive copolymers for cancer immunotherapy.

Despite the tremendous potential of DNA-based cancer vaccines, their efficacious delivery to antigen presenting cells to stimulate both humoral and cellular response remains a major challenge. Although electroporation-based transfection has improved performance, an optimal strategy for safe and pain-free vaccination technique remains elusive. Herein, we report a smart DNA vaccine delivery system in which nanoengineered DNA vaccine was laden on microneedles (MNs) assembled with layer-by-layer coating of ultra-pH-responsive OSM-(PEG-PAEU) and immunostimulatory adjuvant poly(I:C), a synthetic double stranded RNA.