Tofacitinib Citrate Coordination-Based Dual-Responsive/Scavenge Nanoplatform Toward Regulate Colonic Inflammatory Microenvironment for Relieving Colitis.
Jiafeng ZouKun JiangYou ChenYing MaChuanhe XiaWenxing DingMin YaoYiting LinYanzuo ChenYu-Zheng ZhaoFeng GaoPublished in: Advanced healthcare materials (2024)
Ulcerative colitis is an inflammation of the colon characterized by immune dysregulation and intestinal inflammation. Developing safe oral nanomedicines that suppress intestinal inflammation, while modulating colonic inflammatory microenvironment by scavenging reactive oxygen species (ROS) and hydrogen sulfide (H 2 S) is crucial for the effective treatment of colitis. Here, the tofacitinib citrate and copper coordination-based nanoparticle (TF-Cu nanoparticle, T-C) to dual-scavenge ROS and H 2 S by coordination competition is synthesized. Moreover, the coordination of T-C using computer simulation is explored. To enhance the acid stability and inflammatory targeting of T-C, it is encapsulated with hyaluronic acid-modified chitosan, along with a calcium pectinate coating (T-C@HP). Owing to the dual pH/pectinase-responsive characteristics of T-C@HP, the nanoplatform can target inflamed colonic lesions, inhibiting phosphorylated Janus kinase 1. Furthermore, T-C@HP scavenges ROS and H 2 S, as well as increases NADPH levels, which is investigated by combining biosensor (HyPer7 and iNap1/c) and chemical probes. T-C@HP also alleviates colitis by regulating the colonic inflammatory microenvironment through multiple processes, including the modulation of apoptosis, macrophage polarization, tight junction, mucus layer, and intestinal flora. Complemented by satisfactory anti-inflammatory and biosafety results, this nanoplatform represents a promising, effective, and safe treatment option for colitis patients.
Keyphrases
- ulcerative colitis
- oxidative stress
- reactive oxygen species
- cancer therapy
- hyaluronic acid
- dna damage
- drug delivery
- cell death
- stem cells
- photodynamic therapy
- end stage renal disease
- anti inflammatory
- chronic kidney disease
- signaling pathway
- ejection fraction
- endoplasmic reticulum stress
- blood brain barrier
- peritoneal dialysis
- fluorescence imaging
- single molecule
- protein kinase
- atomic force microscopy
- iron oxide
- cell proliferation
- fluorescent probe
- living cells