TopTierJournal,IF15.1 Gut Organoids + Nanosphere: Decoding New Paradigm in Intestinal Immunotherapy

Inflammatory bowel disease (IBD), a chronic intestinal inflammatory disorder, faces limitations in conventional therapies due to significant side effects or inadequate targeting.

Recent advancements in organoid technology (e.g., intestinal organoids) have emerged as pivotal tools for disease mechanism research and drug development, owing to their high fidelity in recapitulating native organ structures (Bar-Ephraim et al., 2020).

A groundbreaking study titled "Programmed micro-nano hierarchical microspheres for the regulation of gut immunity" by Prof. Zhifeng Gu's team at Affiliated Hospital of Nantong University, published in Chemical Engineering Journal, introduces an innovative therapeutic strategy utilizing programmed core-shell micro-nano microspheres. This approach not only effectively modulates gut immunity but also validates anti-inflammatory efficacy through human intestinal organoids, establishing a novel pathway for IBD treatment.

The team engineered hierarchical core-shell microspheres integrating three core technologies:

1.Zein Protective Layer: Resists gastric acid erosion, ensuring intact delivery to the intestinal tract for controlled release.

2.Nanozyme Shell (CeO₂): Scavenges reactive oxygen species (ROS) post-release to rapidly mitigate inflammation.

3.Microalgal Core (Chlamydomonas reinhardtii): Sustains regulatory effects on gut microbiota to enhance anti-inflammatory outcomes.

This stratified delivery system significantly attenuated inflammatory responses in both immune cells and intestinal organoids. In murine IBD models, it demonstrated marked alleviation of pathological changes through immunomodulation, including tissue remodeling, cytokine secretion (e.g., TNF-α, IL-6), macrophage polarization, and gut microbiome composition.

Human intestinal organoids (3D biomimetic models) served as critical validation platforms. Key findings include:

• Barrier Repair: Organoids exhibited intact barrier function (E-cad and Mucin2 expression, Fig 1a). Microsphere treatment effectively inhibited LPS-induced structural atrophy (Figs 1b-c).

• Proliferation Enhancement: Ki67+ cell quantification and immunofluorescence confirmed enhanced epithelial regeneration (Figs 1d-e).

• Inflammation Suppression: Reduced secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β; Figs 1f-h).

Fig 1

Adhering to its mission of "Advancing Science, Serving Humanity," Jiyan Biotech contributes to life sciences through:

Fig 2 Jiyan Biotech Organoid Culture Medium Empowers Intestinal Organoid Models

Fig 3 Jiyan Biotech Human Organoids Complete Medium

1.High-Efficiency Drug Screening: Organoids as alternatives to animal models for accelerated therapeutic evaluation.

2.Personalized Medicine: Patient-derived organoids for tailored treatment strategies.

3.Mechanistic Studies: Elucidating immunomodulatory pathways (e.g., macrophage- microbiota crosstalk) in IBD.

This study not only pioneers new therapeutic avenues for IBD but also underscores the transformative potential of organoid technology in translational medicine. The convergence of nano-engineered delivery systems with organoid platforms promises breakthroughs in treating complex inflammatory disorders.

Reference: Wei et al., Chemical Engineering Journal 505 (2025) 159446
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