A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses
Authors
Xuan Li, Chuan Wang, Leilei Wang, Regina Huang, Wai-Chung Li, Xinna Wang, Sarah Sz, Wah Wong, Zongwei Cai, Ken Cham-Fai Leung, Lijian Jin
Institution
University of Hong Kong, Hong Kong Baptist University,
Country
China
Year
2022
Journal
Journal of Colloid and Interface Science
Abstract
Hypothesis: Precise modulation of immuno-inflammatory response is crucial to control periodontal diseases and related systemic comorbidities. The present nanosystem with the controlled-release and cell-penetrating manner enhances the inflammation modulation effects of baicalein in human gingival epithelial cells (hGECs) for better oral healthcare.
Experiments: We constructed a red-emissive mesoporous silica nanoparticle-based nanosystem with cell-penetrating poly(disulfide) (CPD) capping, through a facile in-situ polymerization approach. It was featured with a glutathione-responsive manner and instant cellular internalization capacity for precisely delivering baicalein intracellularly. Laboratory experiments assessed whether and how the nanosystem per se with the delivered baicalein could modulate immuno-inflammatory responses in hGECs.
Findings: The in-situ polymerized CPD layer capped the nanoparticles and yet controlled the release of baicalein in a glutathione-responsive manner. The CPD coating could facilitate cellular internalization of the nanosystem via endocytosis and thiol-mediated approaches. Notably, the intracellularly released baicalein effectively downregulated the expression of pro-inflammatory cytokines through inhibiting the NF-κB signaling pathway. The nanosystem per se could modulate immuno-inflammatory responses by passivating the cellular response to interlukin-1β. This study highlights that the as-synthesized nanosystem may serve as a novel multi-functional vehicle to modulate innate host response via targeting the NF-κB pathway for precision healthcare.