Tofacitinib Citrate Coordination-Based Dual-Responsive/Scavenge Nanoplatform Toward Regulate Colonic Inflammatory...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Gastroenterology

Background:

• Ulcerative colitis involves immune dysregulation and intestinal inflammation.
• Developing safe oral nanomedicines is crucial for colitis treatment.
• Targeting the colonic inflammatory microenvironment by scavenging reactive oxygen species (ROS) and hydrogen sulfide (H₂S) is a key therapeutic strategy.

Purpose of the Study:

• To synthesize and characterize a novel nanoparticle for dual scavenging of ROS and H₂S.
• To enhance the nanoparticle's stability and targeting capabilities for inflamed colonic lesions.
• To evaluate the nanoplatform's efficacy in treating colitis by modulating the inflammatory microenvironment.

Main Methods:

• Synthesis of tofacitinib citrate and copper coordination-based nanoparticles (T-C).
• Encapsulation of T-C with hyaluronic acid-modified chitosan and a calcium pectinate coating (T-C@HP) for enhanced stability and targeting.
• Utilizing biosensors (HyPer7, iNap1/c) and chemical probes to investigate ROS/H₂S scavenging and NADPH levels.
• Assessing the nanoplatform's effects on apoptosis, macrophage polarization, tight junctions, mucus layer, and intestinal flora in a colitis model.

Main Results:

• The T-C@HP nanoplatform demonstrated dual pH/pectinase-responsive characteristics for targeted delivery to inflamed colonic lesions.
• T-C@HP effectively scavenged ROS and H₂S, increased NADPH levels, and inhibited phosphorylated Janus kinase 1.
• The nanoplatform modulated key aspects of the colonic inflammatory microenvironment, leading to colitis alleviation.
• Satisfactory anti-inflammatory and biosafety profiles were observed.

Conclusions:

• The developed T-C@HP nanoplatform offers a promising, effective, and safe oral treatment for ulcerative colitis.
• Dual scavenging of ROS and H₂S by T-C@HP plays a critical role in regulating the colonic inflammatory microenvironment.
• This nanomedicine approach holds potential for improving therapeutic outcomes in colitis patients.