Probiotic-Drug Conjugates Achieve Synchronized Site-Specific Probiotic Colonization and On-Demand Drug Release...

Area of Science:

• Gastroenterology and Biomedical Engineering
• Drug Delivery Systems
• Microbiology

Background:

• Ulcerative colitis (UC) treatment faces challenges with current probiotic therapies due to poor site-specific colonization and limited codelivery.
• Existing surface-modified probiotics lack selective colonization at lesion sites and struggle with co-delivery of other therapeutics.

Purpose of the Study:

• To develop novel triggerable probiotic-drug conjugates for synchronous, site-specific colonization and on-demand drug release in UC treatment.
• To enhance therapeutic efficacy for ulcerative colitis and its complications through targeted delivery.

Main Methods:

• Engineered *Escherichia coli* Nissle 1917 conjugates with tannic acid-ferric inner layer for adhesion and ROS-responsive pterostilbene-lipid outer coating.
• Oral administration in mouse models of UC, utilizing high reactive oxygen species (ROS) levels in inflamed colons to trigger drug and probiotic release.

Main Results:

• Synchronous release of anti-inflammatory pterostilbene and adhesive probiotics at inflamed colon lesion sites.
• Demonstrated significant therapeutic and prophylactic efficacy in mouse models of UC and associated complications.
• Achieved inflammation suppression and sustained gut microbiota modulation through targeted delivery.

Conclusions:

• The developed probiotic-drug conjugates show significant translational potential for clinical applications in treating gastrointestinal disorders like UC.
• This approach enables combined therapeutic strategies by ensuring site-specific delivery of probiotics and drugs.
• The triggerable release mechanism offers a promising new avenue for managing inflammatory bowel diseases.