Loading Imatinib inside targeted nanoparticles to prevent Bronchiolitis Obliterans Syndrome

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Immunology

Background:

• Bronchiolitis Obliterans Syndrome (BOS) significantly reduces long-term survival in lung transplant recipients.
• Currently, no effective therapies exist for established BOS.
• Nanomedicine offers localized drug delivery to the lungs, potentially increasing efficacy and reducing side effects.

Purpose of the Study:

• To evaluate the efficacy of Imatinib loaded in gold nanoparticles (GNP) functionalized with an anti-CD44 antibody (GNP-HCIm) for treating BOS.
• To assess the impact of GNP-HCIm on lung fibroblasts and in a heterotopic tracheal transplantation (HTT) mouse model.

Main Methods:

• Lung fibroblasts (LFs) were isolated from BOS patients.
• Cytotoxicity, apoptosis, necrosis, and phosphorylated-c-Abl (cAbl-p) levels were measured.
• GNP-HCIm was administered locally via Alzet pumps in an HTT mouse model.

Main Results:

• GNP-HCIm significantly decreased LF viability, induced higher apoptosis and necrosis compared to free Imatinib.
• GNP-HCIm reduced cAbl-p levels.
• In the HTT model, GNP-HCIm significantly reduced tracheal lumen obliteration, apoptosis, and TGF-β signaling.

Conclusions:

• Encapsulating Imatinib into targeted nanoparticles (GNP-HCIm) is a potential strategy to inhibit allograft rejection.
• This approach targets BOS-specific features, offering a novel therapeutic option.