Controlling vaccine kinetics using tannic acid for enhanced humoral immunity.

Despite the success of global vaccination campaigns, vaccine access in low-resource settings is an ongoing challenge. Subunit vaccines are a well-established and clinically scalable intervention, yet they have achieved limited success for poorly immunogenic antigens such as those associated with SARS-CoV-2. Delivery strategies that promote gradual release of subunit vaccines from the injection site offer the potential to improve humoral immunity by enhancing lymph node exposure, however, clinical implementation of this strategy is challenging due to poor scalability and high costs.

Backpack-carrying macrophage immunotherapy for periodontitis.

Cell immunotherapy is a promising therapeutic modality to combat unmet medical needs. Macrophages offer a prominent cell therapy modality since their phenotypic plasticity allows them to perform a variety of roles including defending against pathogens, inducing/suppressing adaptive immunity, and aiding in wound healing. At the same time, this plasticity is a major hurdle in implementation of macrophage therapy.

An ionic liquid-based adjuvant for modulating cellular and humoral immune responses.

Vaccination is an important strategy for the prevention of infectious diseases worldwide. Adjuvants can be incorporated in vaccine formulations to enhance the resultant immune response and subsequently confer more robust protection upon natural infection. While adjuvants have exciting potential to improve vaccination, the landscape of materials employed in clinical adjuvants is small and its expansion is needed to facilitate vaccine development against current and future infectious diseases.

Enhanced visible-light photocatalytic activity of N-doped C/NaTiO/TiO hollow spheres for efficient dye degradation.

Doping and hybridization with other semiconductors are highly effective ways to address the limitations, including their weak response to visible light and significant recombination of photogenerated carriers. In addition, the assisted carbon on the catalyst surface and the structural design have the advantage of being catalytically active. Herein, visible-light-active N-doped C/NaTiO/TiO hollow spheres (denoted as N-C/NTO/TiO HS) were successfully prepared using a facile two-step method and evaluated for methylene blue (MB) aqueous solution degradation under visible-light irradiation.

Dendritic Cell Immune Modulation Polyphenol Membrane Coatings.

Cellular hitchhiking is an emerging strategy for the control of adoptively transferred immune cells. Hitchhiking approaches are primarily mediated by adhesion of nano and microparticles to the cell membrane, which conveys an ability to modulate transferred cells local drug delivery. Although T cell therapies employing this strategy have progressed into the clinic, phagocytic cells including dendritic cells (DCs) are much more challenging to engineer.

Polymer Micropatches as B-Cell Engagers.

B cells, despite their several unique functionalities, remain largely untapped for use as an adoptive cell therapy and are limited to use for antibody production. B cells can be easily sourced, they possess excellent lymphoid-homing capabilities, and they can act as antigen-presenting cells (APCs), offering an alternative to dendritic cells (DCs), which have shown limited efficacy in the clinical setting. Soluble factors such as IL-4 and anti-CD40 antibody can enhance the activation, survival, and antigen-presenting capabilities of B cells; however, it is difficult to attain sufficiently high concentrations of these biologics to stimulate B cells .

Polymer Backpack-Loaded Tissue Infiltrating Monocytes for Treating Cancer.

Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of nonresponders also call for development of antigen-independent therapeutic approaches.

Self-Assembled STING-Activating Coordination Nanoparticles for Cancer Immunotherapy and Vaccine Applications.

The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use in cancer immunotherapy and vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to the immune system. To address these challenges, we developed an immunostimulatory delivery system for STING agonists.

Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy.

Tumour-associated neutrophils can exert antitumour effects but can also assume a pro-tumoural phenotype in the immunosuppressive tumour microenvironment. Here we show that neutrophils can be polarized towards the antitumour phenotype by discoidal polymer micrometric 'patches' that adhere to the neutrophils' surfaces without being internalized. Intravenously administered micropatch-loaded neutrophils accumulated in the spleen and in tumour-draining lymph nodes, and activated splenic natural killer cells and T cells, increasing the accumulation of dendritic cells and natural killer cells.

Cancer vaccines in the clinic.

Vaccines are an important tool in the rapidly evolving repertoire of immunotherapies in oncology. Although cancer vaccines have been investigated for over 30 years, very few have achieved meaningful clinical success. However, recent advances in areas such antigen identification, formulation development and manufacturing, combination therapy regimens, and indication and patient selection hold promise to reinvigorate the field.

Backpack-mediated anti-inflammatory macrophage cell therapy for the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is a debilitating disease with no current therapies outside of acute clinical management. While acute, controlled inflammation is important for debris clearance and regeneration after injury, chronic, rampant inflammation plays a significant adverse role in the pathophysiology of secondary brain injury. Immune cell therapies hold unique therapeutic potential for inflammation modulation, due to their active sensing and migration abilities.

Preclinical characterization of macrophage-adhering gadolinium micropatches for MRI contrast after traumatic brain injury in pigs.

The choroid plexus (ChP) of the brain plays a central role in orchestrating the recruitment of peripheral leukocytes into the central nervous system (CNS) through the blood-cerebrospinal fluid (BCSF) barrier in pathological conditions, thus offering a unique niche to diagnose CNS disorders. We explored whether magnetic resonance imaging of the ChP could be optimized for mild traumatic brain injury (mTBI). mTBI induces subtle, yet influential, changes in the brain and is currently severely underdiagnosed.

Polymer Micropatches as Natural Killer Cell Engagers for Tumor Therapy.

Natural killer (NK) cell therapies have emerged as a potential therapeutic approach to various cancers. Their efficacy, however, is limited by their low persistence and anergy. Current approaches to sustain NK cell persistence include genetic modification, activation via pretreatment, or coadministration of supporting cytokines or antibodies.

A backpack-based myeloid cell therapy for multiple sclerosis.

Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant myeloid function is often observed in MS plaques in the central nervous system (CNS), the role of myeloid cells in therapeutic intervention is currently overlooked. Here, we developed a myeloid cell-based strategy to reduce the disease burden in experimental autoimmune encephalomyelitis (EAE), a mouse model of progressive MS.

STING agonist-loaded mesoporous manganese-silica nanoparticles for vaccine applications.

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnO@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn for vaccination against cancer and SARS-CoV-2.

Induction of T-helper-17-cell-mediated anti-tumour immunity by pathogen-mimicking polymer nanoparticles.

The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (T17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates T17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce T17-cell-mediated anti-tumour responses.

Extracellular matrix degrading enzyme with stroma-targeting peptides enhance the penetration of liposomes into tumors.

Various anti-tumor nanomedicines have been developed based on the enhanced permeability and retention effect. However, the dense extracellular matrix (ECM) in tumors remains a major barrier for the delivery and accumulation of nanoparticles into tumors. While ECM-degrading enzymes, such as collagenase, hyaluronidase, and bromelain, have been used to facilitate the accumulation of nanoparticles, serious side effects arising from the current non-tumor-specific delivery methods limit their clinical applications.

Quantifying intracellular trafficking of silica-coated magnetic nanoparticles in live single cells by site-specific direct stochastic optical reconstruction microscopy.

Background: Nanoparticles have been used for biomedical applications, including drug delivery, diagnosis, and imaging based on their unique properties derived from small size and large surface-to-volume ratio. However, concerns regarding unexpected toxicity due to the localization of nanoparticles in the cells are growing. Herein, we quantified the number of cell-internalized nanoparticles and monitored their cellular localization, which are critical factors for biomedical applications of nanoparticles.

Synergistic Effects of Fluorine and WO Nanoparticles on the Surface of TiO Hollow Spheres for Enhanced Photocatalytic Activity under Visible Light Irradiation.

TiO is an attractive catalyst for the photocatalytic degradation of organic pollutants. However, owing to its large band gap, it can only be activated by ultraviolet (UV) light, which constitutes a small portion of solar energy. Therefore, there has been significant interest in extending its light absorption range from UV to visible light.

Discovery and characterization of high-affinity, potent SARS-CoV-2 neutralizing antibodies via single B cell screening.

Monoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies for the rapid and reliable isolation of these antibodies, especially potent neutralizing antibodies, are critical toward improved COVID-19 response and informed future response to emergent infectious diseases. In this study, single B cell screening was used to interrogate antibody repertoires of immunized mice and isolate antigen-specific IgG1 memory B cells.

Amplifying STING activation by cyclic dinucleotide-manganese particles for local and systemic cancer metalloimmunotherapy.

Nutritional metal ions play critical roles in many important immune processes. Hence, the effective modulation of metal ions may open up new forms of immunotherapy, termed as metalloimmunotherapy. Here, we demonstrate a prototype of cancer metalloimmunotherapy using cyclic dinucleotide (CDN) stimulator of interferon genes (STING) agonists and Mn.

Photothermal therapy combined with neoantigen cancer vaccination for effective immunotherapy against large established tumors and distant metastasis.

Photothermal therapy (PTT) and neoantigen cancer vaccine each offers minimally invasive and highly specific cancer therapy; however, they are not effective against large established tumors due to physical and biological barriers that attenuate thermal ablation and abolish anti-tumor immunity. Here, we designed and performed comparative study using small (~ 50 mm) and large (> 100 mm) tumors to examine how tumor size affects the therapeutic efficiency of PTT and neoantigen cancer vaccine. We show that spiky gold nanoparticle (SGNP)-based PTT and synergistic dual adjuvant-based neoantigen cancer vaccine can efficiently regress small tumors as a single agent, but not large tumors due to limited internal heating and immunosuppressive tumor microenvironment (TME).

Improving STING Agonist Delivery for Cancer Immunotherapy Using Biodegradable Mesoporous Silica Nanoparticles.

Stimulator of interferon genes (STING) activation by intratumoral STING agonist treatment has been recently shown to eradicate tumors in preclinical models of cancer immunotherapy, generating intense research interest and leading to multiple clinical trials. However, there are many challenges associated with STING agonist-based cancer immunotherapy, including low cellular uptake of STING agonists. Here, biodegradable mesoporous silica nanoparticles (bMSN) with an average size of 80 nm are developed for efficient cellular delivery of STING agonists.

Population Pharmacokinetics of Primaquine in the Korean Population.

While primaquine has long been used for malaria treatment, treatment failure is common. This study aims to develop a population pharmacokinetic model of primaquine and its metabolite, carboxyprimaquine, and examine factors influencing pharmacokinetic variability. The data was obtained from a clinical study in 24 Korean subjects randomly assigned to normal and obese groups.

Personalized combination nano-immunotherapy for robust induction and tumor infiltration of CD8 T cells.

Identification of tumor-specific mutations, called neoantigens, offers new exciting opportunities for personalized cancer immunotherapy. However, it remains challenging to achieve robust induction of neoantigen-specific T cells and drive their infiltration into the tumor microenvironment (TME). Here, we have developed a novel polyethyleneimine (PEI)-based personalized vaccine platform carrying neoantigen peptides and CpG adjuvants in a compact nanoparticle (NP) for their spatio-temporally concerted delivery.