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Updated: May 23, 2026
Immunofluorescent Labeling in Nasal Mucosa Tissue Sections of Allergic Rhinitis Rats via Multicolor Immunoassay
Published on: September 22, 2023
A pH-responsive miR-146a-loaded Gel/MSN nanocarrier enhances anti-inflammatory efficacy in allergic rhinitis through
Limei Cui1,2,3,4,5,6, Yujuan Yang1,2,3,4,5,6, Saike Hou1,2,3,4,5,6,7
1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264000, China.
Background:
Allergic rhinitis (AR) is characterized by Th2-dominant inflammation. MicroRNA-146a (miR-146a) is a critical regulator of immune balance in AR, yet its therapeutic translation is severely limited by poor stability and inefficient local delivery. This study aimed to construct a pH-responsive chitosan-coated mesoporous silica (Gel/MSN) nanocarrier for the efficient intranasal delivery of miR-146a, and to evaluate its therapeutic efficacy and underlying mechanisms in AR.
Methods:
The Gel/MSN platform was fabricated and characterized for its structural properties, miR-146a loading efficiency, and pH-triggered release profile. For in vivo evaluation, the nanocomposite was administered intranasally to an AR rat model. Therapeutic efficacy was assessed via behavioral scoring, serum IgE measurements, and the analysis of Th2 cytokines and pyroptosis-related mediators in the nasal mucosa. Biocompatibility was systematically evaluated through 15-day subacute toxicity studies and in vitro cellular assays.
Results:
The synthesized Gel/MSNs possessed a well-defined mesoporous structure with a high specific surface area, enabling efficient miR-146a loading and sustained release under weakly acidic conditions. In vivo, Gel/MSN-miR146a exhibited excellent biocompatibility and markedly alleviated acute nasal symptoms in AR rats, significantly outperforming free miR-146a in reducing serum IgE and Th2 cytokine levels. Mechanistically, the nanocarrier enhanced local miR-146a bioavailability, effectively downregulating the IRAK1/TRAF6/NF-κB axis. Crucially, this treatment strongly suppressed the expression of pyroptosis-related proteins (NLRP3, Caspase-1, GSDMD) and effector cytokines (IL-1β, IL-18). Rescue experiments with the pyroptosis activator nigericin reversed the ameliorative effects of Gel/MSN-miR146a, confirming that pyroptosis suppression is essential for its anti-AR efficacy.
Conclusions:
We successfully developed a biocompatible, pH-responsive Gel/MSN nanocarrier for the efficient intranasal delivery of miR-146a. This platform exerts potent anti-AR effects via a dual mechanism: inhibiting Th2-driven inflammation and suppressing pyroptosis, offering a highly promising and translatable nanotherapeutic strategy for clinical AR management.
Insights
A novel pH-responsive nanocarrier effectively delivered microRNA-146a to treat allergic rhinitis (AR) by reducing inflammation and pyroptosis. This biocompatible platform offers a promising therapeutic strategy for AR management.
Area of Science:
- Biotechnology
- Nanomedicine
- Immunology
Background:
- Allergic rhinitis (AR) involves Th2-dominant inflammation, with microRNA-146a (miR-146a) crucial for immune balance.
- Therapeutic use of miR-146a is hindered by poor stability and inefficient delivery.
- A pH-responsive chitosan-coated mesoporous silica (Gel/MSN) nanocarrier was developed for intranasal miR-146a delivery.
Purpose of the Study:
- To construct and characterize a pH-responsive Gel/MSN nanocarrier for efficient intranasal delivery of miR-146a.
- To evaluate the therapeutic efficacy and underlying mechanisms of Gel/MSN-miR146a in an AR rat model.
- To assess the biocompatibility of the nanocarrier system.
Main Methods:
- Fabrication and characterization of Gel/MSN platform, including miR-146a loading and pH-triggered release.
- Intranasal administration of Gel/MSN-miR146a in an AR rat model.
- Assessment of therapeutic effects (behavioral scoring, IgE, Th2 cytokines, pyroptosis mediators) and biocompatibility (toxicity studies, cellular assays).
Main Results:
- Gel/MSNs demonstrated efficient miR-146a loading and sustained release, with excellent biocompatibility.
- Gel/MSN-miR146a significantly reduced AR symptoms, serum IgE, and Th2 cytokines compared to free miR-146a.
- The treatment downregulated the IRAK1/TRAF6/NF-κB axis and suppressed pyroptosis (NLRP3, Caspase-1, IL-1β, IL-18), confirmed by rescue experiments.
Conclusions:
- A biocompatible, pH-responsive Gel/MSN nanocarrier was successfully developed for efficient intranasal miR-146a delivery.
- The nanocarrier exerts potent anti-AR effects by inhibiting Th2 inflammation and suppressing pyroptosis.
- This platform presents a promising and translatable nanotherapeutic strategy for clinical AR management.
