Evaluation of unmodified human cell-derived extracellular vesicle mitochondrial deoxyribonucleic acid-based biodistribution in rodents.

Recently, extracellular vesicles (EVs) have been developed as therapeutic targets for various diseases. Biodistribution is crucial for EVs intended for therapeutic purposes because it can determine the degree of on- and off-target effects. This study aimed to explore techniques to evaluate the biodistribution of unmodified EVs.

Author Correction: Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis.

[Image: see text]

A nanoadjuvant that dynamically coordinates innate immune stimuli activation enhances cancer immunotherapy and reduces immune cell exhaustion.

Although conventional innate immune stimuli contribute to immune activation, they induce exhausted immune cells, resulting in suboptimal cancer immunotherapy. Here we suggest a kinetically activating nanoadjuvant (K-nanoadjuvant) that can dynamically integrate two waves of innate immune stimuli, resulting in effective antitumour immunity without immune cell exhaustion. The combinatorial code of K-nanoadjuvant is optimized in terms of the order, duration and time window between spatiotemporally activating Toll-like receptor 7/8 agonist and other Toll-like receptor agonists.

A first-in-human study of KMRC011, a potential treatment for acute radiation syndrome, to explore tolerability, pharmacokinetics, and pharmacodynamics.

KMRC011 is a novel Toll-like receptor 5 agonist under development as a treatment for acute radiation syndrome (ARS). The aim of this first-in-human study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of a single intramuscular dose of KMRC011 in healthy subjects. A randomized, single-blind, placebo-controlled, single dose-escalation study was conducted with the starting dose of 5 μg.

Hypoxia Pretreatment Promotes Chondrocyte Differentiation of Human Adipose-Derived Stem Cells via Vascular Endothelial Growth Factor.

Background: Human adipose tissue-derived stem cells (ADSCs) are attractive multipotent stem cell sources with therapeutic potential in various fields requiring repair and regeneration, such as acute and chronically damaged tissues. ADSC is suitable for cell-based therapy, but its use has been hampered due to poor survival after administration. Potential therapeutic use of ADSC requires mass production of cells through in vitro expansion.

Lyophilizable and Multifaceted Toll-like Receptor 7/8 Agonist-Loaded Nanoemulsion for the Reprogramming of Tumor Microenvironments and Enhanced Cancer Immunotherapy.

The low therapeutic efficacy of current cancer immunotherapy is related to nonimmunogenic and immunosuppressive tumor microenvironments (TMEs). To overcome these limitations, both the immune priming of antitumoral lymphocytes and the reprogramming of immunosuppressive factors in TMEs are essential. Here, we suggest a nanoemulsion (NE)-based immunotherapeutic platform that can not only modulate tumor-induced suppression but also induce an effective cell-mediated immune response for T cell proliferation.

The anaphase promoting complex promotes NHEJ repair through stabilizing Ku80 at DNA damage sites.

Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). The choice between these two pathways is largely influenced by cell cycle phases. HDR can occur only in S/G2 when sister chromatid can provide homologous templates, whereas NHEJ can take place in all phases of the cell cycle except mitosis.

Synthetic vaccine nanoparticles target to lymph node triggering enhanced innate and adaptive antitumor immunity.

In this study, synthetic vaccine nanoparticles (SVNPs) that efficiently targeted lymph nodes, where immune responses against foreign antigens are primed, were developed to enhance antitumor immunity. The size (20-70 nm) and surface character (amination) of poly(γ-glutamic acid)-based SVNPs were selected for effective loading and delivery (i.e.

Hyaluronic acid-coated nanoparticles for targeted photodynamic therapy of cancer guided by near-infrared and MR imaging.

In this study, the multifaceted properties of hyaluronic acid (HA) were used for the targeted therapy of cancer by photodynamic therapy (PDT) guided by molecular imaging. Near-infrared (NIR) photosensitizers (Chlorin e6; Ce6) were encapsulated into poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with HA that can act as CD44 targeting ligand. The abundant carboxylate groups of HA also enabled the chelation of gadolinium ions (Gd), T1-weighted MRI contrast agents, on the surface of PLGA NPs.

Raspberry-like poly(γ-glutamic acid) hydrogel particles for pH-dependent cell membrane passage and controlled cytosolic delivery of antitumor drugs.

In this research, we synthesized bioderived poly(amino acid) hydrogel particles that showed pH-dependent membrane-disrupting properties and controlled cytosolic delivery of antitumor drugs. Poly(γ-glutamic acid) (γ-PGA) that has been produced extensively using bacteria, especially those of species, was modified with cholesterol (γ-PGA/Chol), and the γ-PGA/Chol conjugates were used to form polymeric nanoparticles the size of 21.0±1.

Hyaluronic acid-supported combination of water insoluble immunostimulatory compounds for anti-cancer immunotherapy.

A novel powder-form combination adjuvant system containing two immunostimulatory compounds was firstly developed and evaluated as a therapeutic intervention for cancer immunotherapy. With the help of hyaluronic acid (HA), water insoluble monophosphoryl lipid A (MPL), QS21 and imiquimod (R837), could be easily dispersed in aqueous solution and lyophilized as powder-form, which have an advantage in room-temperature storage stability compared with those conventional liquid formulation that requires cold storage. Two kinds of HA-based combination vaccine adjuvants (HA/MPL/QS21, HMQ and HA/MPL/R837, HMR) contributed to the increase of both humoral and cellular immunity, which is very important for efficient cancer immunotherapy.

Injectable and Pathogen-Mimicking Hydrogels for Enhanced Protective Immunity against Emerging and Highly Pathogenic Influenza Virus.

Seasonal emerging infectious diseases such as influenza A impose substantial risk and need new translational strategies to achieve active immunomodulation. Here, a novel injectable pathogen-mimicking hydrogel (iPMH) that can enhance both cellular and humoral immune responses is suggested. By the help of poly(γ-glutamic acid) that has abundant carboxylate groups and dispersion helper function, hydrophobic immunostimulatory 3-O-desacyl-4'-monophosphoryl lipid A (MPLA) molecules and viral antigens (PR8, W150) can be successfully combined as pathogen-mimicking adjuvants.

Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response.

Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL) immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI)-coated polymer nanoparticles (NPs) as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide) (PLGA) NPs containing ovalbumin (OVA) by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI.

An Electrostatically Self-Assembled Ternary Nanocomplex as a Non-Viral Vector for the Delivery of Plasmid DNA into Human Adipose-Derived Stem Cells.

In this study, we developed electrostatically self-assembled ternary nanocomplexes as a safe and effective non-viral vector for the delivery of plasmid DNA (pDNA) into human adipose-derived stem cells (hASCs). Although polyethylenimine (PEI) polymers initially showed excellent performance as gene delivery carriers, their broad use has been limited by cytotoxicity resulting from their strong positive charge. To reduce the cytotoxicity, we utilized anionic hyaluronic acid (HA) as a corona layer material for pDNA/PEI binary nanocomplexes.

Evaluation of hyaluronic acid-based combination adjuvant containing monophosphoryl lipid A and aluminum salt for hepatitis B vaccine.

Here, monophosphoryl lipid A (MPLA) and aluminum salt (Alum) were introduced into a hyaluronic acid (HA)-based combination vaccine adjuvant for hepatitis B vaccine (HBV). Although Alum is a well-known hepatitis B vaccine adjuvant that induces an enhanced humoral immune response, it cannot induce the cellular immune responses. On the other hand, MPLA has been generally reported to promote IFN-γ production via antigen-specific CD4(+) T cells, but it is not water soluble as a result of its long hydrophobic alkyl chains.

Magnetophoretic circuits for digital control of single particles and cells.

The ability to manipulate small fluid droplets, colloidal particles and single cells with the precision and parallelization of modern-day computer hardware has profound applications for biochemical detection, gene sequencing, chemical synthesis and highly parallel analysis of single cells. Drawing inspiration from general circuit theory and magnetic bubble technology, here we demonstrate a class of integrated circuits for executing sequential and parallel, timed operations on an ensemble of single particles and cells. The integrated circuits are constructed from lithographically defined, overlaid patterns of magnetic film and current lines.

Evaluation of the novel near-infrared fluorescence tracers pullulan polymer nanogel and indocyanine green/γ-glutamic acid complex for sentinel lymph node navigation surgery in large animal models.

Background: This study aimed to examine tracers designed to overcome the disadvantages of indocyanine green (ICG), which disperses quickly to multiple lymph nodes, using a near-infrared (NIR) imaging system in animal models.

Methods: Diluted ICG, ICG/poly-γ-glutamic acid (PGA) complex, and IRDye900-conjugated pullulan-cholesterol nanoprobe "near-infrared polynagogel" (NIR-PNG) were injected into the stomachs of dogs and pigs, and the patterns of dispersion were observed using an NIR imaging system. To compare retention times, fluorescence signals were evaluated in the stomach and small bowel of animals 1 week after injection.

Anti-proliferative effect of honokiol in oral squamous cancer through the regulation of specificity protein 1.

Honokiol (HK), a novel plant-derived natural product, is a physiologically activated compound with polyphenolic structure, and has been identified to function as an anticancer agent. It has been widely used in several diseases as a traditional medicine for a long time. We investigated whether HK could show anticancer effects on two oral squamous cell lines (OSCCs), HN-22 and HSC-4.

Polymer nanomicelles for efficient mucus delivery and antigen-specific high mucosal immunity.

Micelles for mucosal immunity: A mucosal vaccine system based on γ-PGA nanomicelles and viral antigens was synthesized. The intranasal administration of the vaccine system induces a high immune response both in the humoral and cellular immunity (see picture).

In vivo imaging of islet transplantation using PLGA nanoparticles containing iron oxide and indocyanine green.

Purpose: We determined whether poly(lactic-co-glycolic acid) nanoparticles would be a useful reagent for the successful monitoring of isolated islets by magnetic resonance imaging and optical imaging systems, without clinically relevant toxicity in vitro or in vivo.

Methods: We used iron oxide for MR imaging and a cyanide dye approved by the Food and Drug Administration (indocyanine green) for optical imaging and estimated the in vivo detection of transplanted pancreatic islets.

Results: The poly(lactic-co-glycolic acid) nanoparticles were associated with the islets in vitro and were successfully detected by 4.

Near-infrared emitting polymer nanogels for efficient sentinel lymph node mapping.

Sentinel lymph node (SLN) mapping has been widely used to predict the metastatic spread of primary tumor to regional lymph nodes in clinical practice. In this research, a new near-infrared (NIR)-emitting polymer nanogel (NIR-PNG) having a hydrodynamic diameter of about 30 nm, which is optimal for lymph node uptake, was developed. The NIR-emitting polymer nanoprobes were designed and synthesized by conjugating IRDye800 organic dye to biodegradable pullulan-cholesterol polymer nanogels.