1. A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses
- Author
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Xuan Li, Chuan Wang, Leilei Wang, Regina Huang, Wai-Chung Li, Xinna Wang, Sarah Sze Wah Wong, Zongwei Cai, Ken Cham-Fai Leung, Lijian Jin, The University of Hong Kong (HKU), Hong Kong Baptist University (HKBU), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and This work was supported by the Hong Kong Research Grants Council (GRF No. 17122918 & 17119819) and the Modern Dental Laboratory/HKU Endowment Fund to L.J. Jin as well as the Key Research Partnership Scheme of HKBU (RC-KRPS-20-21/02) to K.C.-F. Leung.
- Subjects
Mesoporous silica nanoparticles ,MESH: Drug Delivery Systems ,MESH: Immunomodulation ,MESH: Silicon Dioxide ,Polymerization ,Biomaterials ,Immunomodulation ,Colloid and Surface Chemistry ,Drug Delivery Systems ,MESH: Porosity ,Intracellular drug delivery ,Humans ,[CHIM]Chemical Sciences ,MESH: Disulfides ,Disulfides ,MESH: Periodontal Diseases ,Periodontal Diseases ,MESH: Glutathione ,MESH: Humans ,Silicon Dioxide ,Glutathione ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,MESH: Flavanones ,Cell-penetrating poly(disulfide)s ,MESH: Polymerization ,Flavanones ,Nanoparticles ,Periodontal disease ,Porosity ,MESH: Nanoparticles - Abstract
International audience; HypothesisPrecise 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.ExperimentsWe 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.FindingsThe 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.
- Published
- 2022
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