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Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
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Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
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Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
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Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
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In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
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Orally Delivered Tolerogenic Nanotherapeutic for Targeted Colitis Therapy via ROS Scavenging and Treg/Th17

Dong Kwang Min1, Xin Wang Mo1, Jaeyun Kim1,2,3,4,5

  • 1School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.

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Summary

A novel nanotherapeutic combines prebiotics and reactive oxygen species (ROS) scavenging to treat inflammatory bowel disease (IBD). This treatment targets gut inflammation, restoring immune balance and promoting gut healing.

Keywords:
inflammatory bowel diseasemesoporous polydopamine nanoparticlemetforminprebiotictannic acid

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Area of Science:

  • Biomedical Engineering
  • Immunology
  • Nanotechnology

Background:

  • Inflammatory bowel disease (IBD) therapy struggles to restore gut immune homeostasis.
  • Targeted delivery of therapeutic agents to inflamed colonic sites remains a challenge.

Purpose of the Study:

  • To develop a prebiotic-integrated, reactive oxygen species (ROS)-scavenging nanotherapeutic for targeted IBD treatment.
  • To evaluate the efficacy of this nanotherapeutic in an experimental colitis model.

Main Methods:

  • Porous polydopamine nanoparticles (PNPs) were functionalized with metformin (Met) and tannic acid (TA) to create TA-Met-PNPs.
  • TA-Met-PNPs were administered orally to a dextran sulfate sodium (DSS)-induced colitis mouse model.
  • Cellular uptake, immune responses, ROS scavenging, and gut microbiota changes were analyzed.

Main Results:

  • TA-Met-PNPs adhered to inflamed colonic lesions and were taken up by macrophages and dendritic cells, reducing inflammation.
  • The nanotherapeutic promoted tolerogenic dendritic cell induction via ROS scavenging in mesenteric lymph nodes (MLNs).
  • Enhanced butyrate production and an increased regulatory T (Treg) to T-helper 17 (Th17) cell ratio were observed, restoring immune tolerance.

Conclusions:

  • Prebiotic-combined ROS-scavenging nanotherapeutics can effectively remodel the gut microenvironment.
  • This approach offers a promising strategy for treating IBD by inducing an immunosuppressive state.