Noninvasive ROS imaging and drug delivery monitoring in the tumor microenvironment.

Reactive oxygen species (ROS) that are overproduced in certain tumors can be considered an indicator of oxidative stress levels in the tissue. Here, we report a magnetic resonance imaging (MRI)-based probe capable of detecting ROS levels in the tumor microenvironment (TME) using ROS-responsive manganese ion (Mn)-chelated, biotinylated bilirubin nanoparticles (Mn@bt-BRNPs). These nanoparticles are disrupted in the presence of ROS, resulting in the release of free Mn, which induces T1-weighted MRI signal enhancement.

Longitudinal Magnetic Resonance Imaging with ROS-Responsive Bilirubin Nanoparticles Enables Monitoring of Nonalcoholic Steatohepatitis Progression to Cirrhosis.

Despite the vital importance of monitoring the progression of nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), an efficient imaging modality that is readily available at hospitals is currently lacking. Here, a new magnetic-resonance-imaging (MRI)-based imaging modality is presented that allows for efficient and longitudinal monitoring of NAFLD and NASH progression. The imaging modality uses manganese-ion (Mn)-chelated bilirubin nanoparticles (Mn@BRNPs) as a reactive-oxygen-species (ROS)-responsive MRI imaging probe.

Anti-inflammatory Glycocalyx-Mimicking Nanoparticles for Colitis Treatment: Construction and In Vivo Evaluation.

Common medications for treating inflammatory bowel disease (IBD) have limited therapeutic efficacy and severe adverse effects. This underscores the urgent need for novel therapeutic approaches that can effectively target inflamed sites in the gastrointestinal tract upon oral administration, exerting potent therapeutic efficacy while minimizing systemic effects. Here, we report the construction and in vivo therapeutic evaluation of a library of anti-inflammatory glycocalyx-mimicking nanoparticles (designated GlyNPs) in a mouse model of IBD.

Bilirubin Nanomedicine Rescues Intestinal Barrier Destruction and Restores Mucosal Immunity in Colitis.

Inflammatory bowel disease (IBD) manifests as intestinal barrier destruction, mucosal immunity dysregulation, and disrupted gut microbiome homeostasis. Conventional anti-inflammatory medications for IBD therapy partially alleviate symptoms but are unable to restore normal barrier and immune function. Here, we report a nanomedicine comprising bilirubin (BR)-attached low-molecular-weight, water-soluble chitosan nanoparticles (LMWC-BRNPs), that promotes restoration of the intestinal barrier, mucosal immunity, and the gut microbiome, thereby exerting robust therapeutic efficacy.

Post Transplantation Bilirubin Nanoparticles Ameliorate Murine Graft Versus Host Disease a Reduction of Systemic and Local Inflammation.

Allogeneic stem cell transplantation is a curative immunotherapy where patients receive myeloablative chemotherapy and/or radiotherapy, followed by donor stem cell transplantation. Graft versus host disease (GVHD) is a major complication caused by dysregulated donor immune system, thus a novel strategy to modulate donor immunity is needed to mitigate GVHD. Tissue damage by conditioning regimen is thought to initiate the inflammatory milieu that recruits various donor immune cells for cross-priming of donor T cells against alloantigen and eventually promote strong Th1 cytokine storm escalating further tissue damage.

Photomedicine based on heme-derived compounds.

Photoimaging and phototherapy have become major platforms for the diagnosis and treatment of various health complications. These applications require a photosensitizer (PS) that is capable of absorbing light from a source and converting it into other energy forms for detection and therapy. While synthetic inorganic materials such as quantum dots and gold nanorods have been widely explored for their medical diagnosis and photodynamic (PDT) and photothermal (PTT) therapy capabilities, translation of these technologies has lagged, primarily owing to potential cytotoxicity and immunogenicity issues.

Glutathione-Responsive Gold Nanoparticles as Computed Tomography Contrast Agents for Hepatic Diseases.

Glutathione (GSH) is produced at high levels in the normal liver, but its production is considerably reduced under certain pathological conditions. Accordingly, an imaging probe capable of visualizing the altered GSH level in the liver would be a useful tool for monitoring hepatic functions or diseases. Here, we report a gold nanoparticle (AuNP)-based computed tomography (CT) contrast agent that undergoes a change in colloidal stability in response to GSH levels, resulting in differential CT signal intensity between normal (higher intensity) and pathological (lower intensity) livers, enabling imaging of hepatic function.

Bilirubin Nanoparticles Protect Against Cardiac Ischemia/Reperfusion Injury in Mice.

Background Ischemia/reperfusion (I/R) injury causes overproduction of reactive oxygen species, which are the major culprits of oxidative stress that leads to inflammation, apoptosis, myocardial damage, and dysfunction. Bilirubin acts as a potent endogenous antioxidant that is capable of scavenging various reactive oxygen species. We have previously generated bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol-conjugated bilirubin.

Biomimetic lipid Nanocomplexes incorporating STAT3-inhibiting peptides effectively infiltrate the lung barrier and ameliorate pulmonary fibrosis.

Activation of signal transducer and activator of transcription 3 (STAT3) under conditions of inflammation plays a crucial role in the pathogenesis of life-threatening pulmonary fibrosis (PF), initiating pro-fibrotic signaling following its phosphorylation. While there have been attempts to interfere with STAT3 activation and associated signaling as a strategy for ameliorating PF, potent inhibitors with minimal systemic toxicity have yet to be developed. Here, we assessed the in vitro and in vivo therapeutic effectiveness of a cell-permeable peptide inhibitor of STAT3 phosphorylation, designated APTstat3-9R, for ameliorating the indications of pulmonary fibrosis.

Association between the Intake of Fermented Soy Products and Hypertension Risk in Postmenopausal Women and Men Aged 50 Years or Older: The Korea National Health and Nutrition Examination Survey 2013-2018.

Sodium intake is positively associated with hypertension risk; however, it is not clear whether there is an association between the intake of fermented soy products, a major source of salt, and blood pressure (BP). This study aimed to investigate the hypothesis that hypertension risk and BP were negatively associated with the intake of fermented soy products but not with the intake of sodium from fermented soy products. This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey (2013-2018).

Sequential and Timely Combination of a Cancer Nanovaccine with Immune Checkpoint Blockade Effectively Inhibits Tumor Growth and Relapse.

We describe a small lipid nanoparticle (SLNP)-based nanovaccine platform and a new combination treatment regimen. Tumor antigen-displaying, CpG adjuvant-embedded SLNPs (OVA -SLNP@CpG) were prepared from biocompatible phospholipids and a cationic cholesterol derivative. The resulting nanovaccine showed highly potent antitumor efficacy in both prophylactic and therapeutic E.

PEGylated Bilirubin-coated Iron Oxide Nanoparticles as a Biosensor for Magnetic Relaxation Switching-based ROS Detection in Whole Blood.

: Magnetic relaxation switching (MRSw) induced by target-triggered aggregation or dissociation of superparamagnetic iron oxide nanoparticles (SPIONs) have been utilized for detection of diverse biomarkers. However, an MRSw-based biosensor for reactive oxygen species (ROS) has never been documented. : To this end, we constructed a biosensor for ROS detection based on PEGylated bilirubin (PEG-BR)-coated SPIONs (PEG-BR@SPIONs) that were prepared by simple sonication via ligand exchange.

Dll4 Suppresses Transcytosis for Arterial Blood-Retinal Barrier Homeostasis.

Rationale: Central nervous system has low vascular permeability by organizing tight junction (TJ) and limiting endothelial transcytosis. While TJ has long been considered to be responsible for vascular barrier in central nervous system, suppressed transcytosis in endothelial cells is now emerging as a complementary mechanism. Whether transcytosis regulation is independent of TJ and its dysregulation dominantly causes diseases associated with edema remain elusive.

A vector system for ABC transporter-mediated secretion and purification of recombinant proteins in Pseudomonas species.

Pseudomonas fluorescens is an efficient platform for recombinant protein production. P. fluorescens has an ABC transporter secreting endogenous thermostable lipase (TliA) and protease, which can be exploited to transport recombinant proteins across the cell membrane.