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A nanoparticulate dual scavenger for targeted therapy of inflammatory bowel disease

Shi, Chengxin; Dawulieti, Jianati; Shi, Feiyu; Yang, Chao; Qin, Qian; Shi, Tongfei; Wang, Lizhao; Hu, Hanze; Sun, Madi; Ren, Li; Chen, Fangman; Zhao, Yawei; Liu, Feng; Li, Mingqiang; Mu, Lijun; Liu, Dan; Shao, Dan*; Leong, Kam W.*; She, Junjun*
Science Citation Index Expanded
西安交通大学; 中山大学; 1

摘要

A therapeutic strategy that targets multiple proinflammatory factors in inflammatory bowel disease (IBD) with minimal systemic side effects would be attractive. Here, we develop a drug-free, biodegradable nanomedicine that acts against IBD by scavenging proinflammatory cell-free DNA (cfDNA) and reactive oxygen species (ROS). Polyethylenimine (PEI) was conjugated to antioxidative diselenide-bridged mesoporous organosilica nanoparticles (MONs) to formulate nanoparticles (MON-PEI) that exhibited high cfDNA binding affinity and ROS-responsive degradation. In ulcerative colitis and Crohn's disease mouse colitis models, orally administered MON-PEI accumulated preferentially in the inflamed colon and attenuated colonic and peritoneal inflammation by alleviating cfDNA-and ROS-mediated inflammatory responses, allowing a reduced dose frequency and ameliorating colitis even after delayed treatment. This work suggests a new nanomedicine strategy for IBD treatment.

关键词

ACID-BINDING POLYMERS ULCERATIVE-COLITIS OXIDATIVE STRESS DNA BIOLOGICS PATTERNS PROTECT CELLS