Polysaccharide-based inflammatory microenvironment-responsive nanocarriers for ulcerative colitis: Advances in design, mechanisms, and therapeutic applications.

The worldwide incidence of ulcerative colitis (UC) continues to rise, presenting a growing public health challenge due to its multifactorial etiology and limited therapeutic options. While current therapeutic regimens can alleviate symptoms, they are plagued by constrained efficacy and significant side effects. Advances in nanotechnology have catalyzed the development of polysaccharide-based inflammatory microenvironment-responsive nanocarriers (PIMRNs), offering novel opportunities for UC management. PIMRNs exhibit excellent bioactivity, biocompatibility, and multifunctional modulation capabilities. Their structural design enables precise targeting and spatiotemporally controlled drug release, which can be specifically triggered by the distinctive inflammatory microenvironment of UC, including elevated reactive oxygen species, dysregulated pH, and enzyme overexpression. This microenvironment-responsive delivery system synergistically enhances therapeutic efficacy while minimizing off-target adverse effects. This review outlines the dynamic inflammatory microenvironment in UC and highlights its pivotal role in guiding the design of PIMRNs. It systematically summarizes recent advances in PIMRNs for UC treatment, articulates fundamental design principles along with optimization strategies to improve their performance, and discusses key challenges and future directions for their clinical translation. Through continued refinement, PIMRNs hold the potential to transform current UC treatment paradigms and enable precision therapy for a range of inflammatory disorders.