Targeted C3G delivery by engineered milk exosomes for effective therapy in microplastics-induced colitis

Sep 29, 2026

Uploaded by Terk

Microplastic polystyrene ingestion via the food chain provokes chronic colitis and lacks consistently effective interventions. Cyanidin-3-O-glucoside (C3G) from red bayberry alleviates colitis but is limited by low colonic bioavailability after oral dosing. This work engineers raw milk-derived exosomes conjugated with an F6 antibody against colonic MAdCAM-1 to form C3G@Exo-F6. C3G@Exo-F6 improves stability, promotes colon cell uptake, suppresses inflammation, restores gut barrier integrity, and reshapes the gut microbiota in PS-induced chronic colitis mice. Mechanistically, sequencing and metabolomics link Lactobacillus enrichment to elevated L-proline, which inhibits the TLR-4/COX-2 inflammatory pathway via NR1D1.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Microplastics polystyrene exposure and colon impacts

Gut microbiota imbalance and inflammatory responses

Existing treatments and limitations

Food-derived bioactives and red bayberry background

Materials Today Bio 36 (2026) 102639 Contents lists available at ScienceDirect Materials Today Bio journal [homepage:](homepage: www.journals.elsevier.com/materials-today-bio)[ www.journals.elsevier.com/materials-today-bio](homepage: www.journals.elsevier.com/materials-today-bio) | Targeted C3G delivery by engineered milk exosomes for effective therapy in microplastics-induced colitis
Yuanjie Wu b,1, Wen Chena,b,*,1, Xiang Ye b,d, Xingkai Hao a,b, Yuhao Wen b ,
Jian Wu a,b, Danyang Li c, Lizhou Xu a,b,**
a College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, China
b ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311215, China
c Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research, China
d College of Food and Bioengineering, Fujian Polytechnic Normal University, Longjiang Street, Fuqing, Fujian, 310300, China | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords:
Chronic colitis Cyanidin-3-O-glucoside Raw milk derived-exosomes Gut microbiome
Chemical modification | | Microplastic polystyrene (PS) ingestion through the food chain induces chronic colitis, with no effective intervention strategy, posing a public health concern globally. Cyanidin-3-O-glucoside (C3G), an anthocyanin abundant in red bayberry, can alleviate colitis while has limited therapeutic efficacy due to its low colonic bioavailability after oral administration. Targeted delivery strategies may enhance colonic C3G concentration and improve its therapeutic efficacy. Exosomes are engineerable nanoparticles with excellent biocompatibility and unique biological activities. In this study, the mucosal addressin cell adhesion molecule 1 (MAdCAM-1, F6) antibody, which specifically binds to colonic inflammatory MAdCAM-1 marker, was conjugated to the raw milk derived-exosome surface to form C3G@Exo-F6, aiming to enhance colonic C3G targeting. In vitro, C3G@Exo-F6 exhibited significantly enhanced stability in simulated digests and was more efficiently taken up by colon cells. Ina PS-induced in vivo chronic colitis mice model, C3G@Exo-F6 demonstrated superior efficiency compared to C3G only by inhibiting inflammatory responses, restoring gut barriers integrity and modulating the gut microbiota. Mechanically, 16S rRNA sequencing and untargeted metabolomics demonstrated that C3G@Exo-F6 significantly increased the Lactobacillus abundance and subsequently upregulated the metabolic L-Proline level. Molecular docking identified that L-Proline binds effectively to nuclear receptor subfamily 1 group D member 1 (NR1D1) protein, inhibiting the expression of inflammatory TLR-4/COX-2 pathway. Additionally, Exo-F6 carries exhibited similar therapeutic effects, indicating that exosomes derived from raw milk possess collaborative antiinflammatory activities. Collectively, these findings emphasize the potential of C3G@Exo-F6 for targeted treatment of chronic colitis, providing a food-derived therapeutic approach for microplastics-induced colonic inflammation. | 1. Introduction Microplastic polystyrene (PS), as typical microplastic particles with a diameter less than 5 mm originating from plastic decomposition [1,2], PS can be ingested by various crops or animals and then accumulate in the human digestive tract [3,4]. Significant PS contamination is present in drinking water and plastic-packaged food, which people consume daily [5]. Eventually, PS have been detected in human blood and feces; with analysis of samples from 22 healthy volunteers confirming their presence [6]. This finding supports that as apex consumers in the food chain, PS are likely to accumulate in human digestive systems [7], some are excreted with feces, while others remain in the gut mucosa, leading to adverse impacts on the colon such as inflam

FAQs

Why is microplastic-induced colitis difficult to treat effectively?

Microplastics such as polystyrene accumulate in the digestive tract and disrupt gut microbiota homeostasis, which can trigger persistent inflammation and immune responses. Reported intervention strategies remain insufficient, motivating targeted approaches.

How does C3G@Exo-F6 enhance delivery of cyanidin-3-O-glucoside?

C3G@Exo-F6 is created by conjugating an MAdCAM-1 (F6) antibody onto raw milk-derived exosome surfaces, aiming to improve colonic targeting. It shows improved stability in simulated digests and more efficient uptake by colon cells.

What mechanistic evidence supports C3G@Exo-F6’s anti-inflammatory effect?

In PS-induced chronic colitis mice, 16S rRNA sequencing and untargeted metabolomics indicate that C3G@Exo-F6 increases Lactobacillus abundance and upregulates L-proline. Molecular docking suggests L-proline binds NR1D1 and inhibits the inflammatory TLR-4/COX-2 pathway.

Sep 29, 2026

Uploaded by Terk