Near-Infrared-Responsive Poly(lactic- <i>co</i> -glycolic acid)-Coated Prussian Blue Nanocubes Promote Alleviation of Colitis in an Inflammatory Bowel Disease Model via Multiplexed Real-Time Photoacoustic Imaging

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by persistent gastrointestinal inflammation and epithelial damage in the colon and rectum, often resulting in rectal bleeding and an increased risk of colorectal cancer. Existing therapies are still insufficient to fully reverse mucosal injury or restore normal physiological homeostasis. This study aimed to develop a nanoparticle-based therapeutic platform as a potential alternative treatment for UC. Near-infrared-active Prussian blue nanocubes (PBNCs) coated with poly lactic-<i>co</i>-glycolic acid (PLGA) were synthesized. Their physicochemical properties were evaluated using TEM, XPS, FTIR, XRD, zeta potential analysis, EDAX, and TGA to verify the cube morphology, uniform size distribution, thermal stability, crystallinity, and surface functionality. Biocompatibility and therapeutic effects were tested through hemocompatibility assays, cytotoxicity tests, live/dead staining, immunoblotting, and annexin V-PI analyses to determine antiproliferative and apoptosis-inducing capabilities. PLGA-PBNCs showed a dose-dependent inhibition of cell proliferation and induction of apoptosis. In a DSS-induced UC mouse model, orally administered nanoparticles reduced oxidative stress, improved oxygen saturation, promoted mucosal healing, and normalized colon lumen diameter and length, further supported by photoacoustic imaging. The overall findings highlight the therapeutic potential of PLGA-coated PBNCs as a nanomedicine-based approach for UC management, opening innovative avenues for the management of UC-induced colorectal cancer.