Title : Nebulized mesenchymal stem cell-derived exosomes encapsulating interferon-α2b: A synergistic strategy for targeted treatment of severe viral pneumonia
Abstract:
Background: Severe viral pneumonias (e.g.,influenza, RSV) lack effective localized treatments.While Interferon-α (IFN-α) is a potent antiviral, its clinical utility via inhalation is limited by rapid degradation, poor lung retention, and systemic toxicity. We developed Exo-Aero α, a novel translational platform using mesenchymal stem cell-derived exosomes (MSC-Exos) as bio-nanocarriers to enhance IFN-α2b delivery and provide synergistic lung repair.
Methods: MSC-Exos were harvested from P3-generation stem cells and loaded with IFN-α2b (100-200 IU/mL) via a proprietary physical-chemical loading process. The formulation was stabilized through a specialized lyophilization technique (10Pa/-50°C). Physicochemical properties, including particle size (NTA) and bioactivity retention, were validated. In vivo efficacy was tested in a lethal-dose H1N1 influenza mouse model using a precision nebulization system.
Results: The Exo-Aero α formulation maintained a stable particle size of 86.2 ± 21.6 nm with over 95% bioactivity retention post-nebulization. In the lethal viral challenge model, the synergistic group achieved a 100% survival rate, significantly outperforming IFN-α2b monotherapy (32%) and MSC-Exos alone (60%). Mechanism studies revealed a "1+1>2" effect: IFN-α2b suppressed viral replication via the JAK-STAT pathway, while MSC-Exos modulated the pulmonary immune microenvironment, suppressed the cytokine storm, and promoted alveolar epithelial regeneration. Preliminary safety assessments in pilot translational studies support its high biocompatibility.
Conclusion: Exo-Aero α successfully addresses the stability and targeted delivery hurdles of biological drugs for respiratory infections. By integrating potent antiviral action with endogenous tissue repair, this "Trinity" platform provides a promising, scalable candidate for the clinical management of severe viral pneumonia and acute lung injury.
