Enhancing Fibrotic Lung Research: How baseclick’s Sugar-Ligand Technology Advances Drug Targeting
Pulmonary fibrosis remains one of the most challenging and poorly treatable chronic diseases. Despite promising in vitro findings, many anti-fibrotic compounds fail in clinical translation due to poor delivery and lack of tissue specificity.
A recent study by Jordan et al. (2025) explored the repurposing of carvedilol, a β-adrenergic receptor blocker, for the treatment of fibrotic lung disease. The authors demonstrated clear anti-fibrotic effects in lung fibroblasts, including reduced proliferation, ECM production, and ROS signaling. However, its limited efficacy in complex ex vivo lung tissue (e.g., precision-cut lung slices) raised important translational questions chiefly, how can we improve delivery to disease-relevant cells?
This is where baseclick’s sugar-ligand functionalization platform enters the conversation.
The Challenge: Delivery in a Complex Microenvironment
In pulmonary fibrosis, fibrotic lesions form a dense matrix populated by activated fibroblasts, myofibroblasts, and pro-inflammatory immune cells. Carvedilol showed strong cellular effects in fibroblasts but was less effective in ex vivo tissue, partly due to:
- Poor tissue penetration
- Non-specific distribution
- Lack of selective uptake by fibrotic cells
To truly evaluate or utilize such drugs in complex tissue environments or ultimately in patients, we need targeted delivery mechanisms that recognize and act on the right cell types.
The baseclick Solution: Sugar-Ligand Targeting
baseclick offers a versatile glycan-functionalization platform, originally developed for precise detection of DNA synthesis via EdU analogs. This same chemistry is now being applied to drug molecules to enable:
- Cell-specific targeting through sugar–lectin interactions
- Click chemistry-based conjugation of sugars to small molecules
- Improved uptake by fibroblasts and other disease-relevant cells in fibrotic tissue
Many fibrotic cells such as lung fibroblasts, alveolar epithelial cells, and alternatively activated macrophages overexpress lectins that bind sugar ligands like mannose, galactose, or GlcNAc. These biological “handles” can be used to direct drugs exactly where they are needed.
A Translational Upgrade for Carvedilol?
Imagine re-formulating carvedilol with a mannose ligand using baseclick’s modular chemistry. This targeted version could be:
- Preferentially taken up by activated lung fibroblasts (via CD206/MRC1 receptors)
- More effective in precision-cut lung slice models, where diffusion and cell targeting are barriers
- A step closer to inhalable, cell-targeted delivery for human use
Additionally, pairing this strategy with sugar-modified EdU analogs enables cell-type-specific proliferation studies, improving readouts for drug screening and mechanism-of-action studies.
From Concept to Clinic
How this strengthens the findings of Jordan et al. (2025):
- Validates carvedilol’s anti-fibrotic activity in more physiologically relevant models
- Improves delivery in ex vivo and in vivo settings, where traditional formulations underperform
- Opens the door to dual-labeled therapeutic/proliferation probes for advanced tissue modeling
Looking Ahead
Targeted delivery is not just a pharmacokinetic upgrade; it’s a paradigm shift in how we approach fibrosis and other chronic tissue diseases.
With baseclick’s sugar-ligand platform, researchers can go beyond in vitro efficacy and tackle the real bottlenecks in translation: specificity, selectivity, and tissue relevance.
If you are working on anti-fibrotic compounds, inhaled therapeutics, or tissue-specific delivery, it is worth exploring how baseclick’s chemistry can accelerate your development pipeline.
About baseclick
baseclick GmbH develops proprietary click chemistry tools for molecular biology, diagnostics, and drug delivery. Their platform is based on bio-orthogonal chemistry and enables rapid, clean, and customizable functionalization of biomolecules, including nucleosides, peptides, and small molecules.
Interested in collaboration or pilot studies? Reach out to baseclick or [tag your contact here] to explore how we can work together on cell-specific delivery systems in lung disease and beyond.
References
- Jordan et al. (2025). Repurposing of the small-molecule adrenoreceptor-inhibitor carvedilol for treatment of the fibrotic lung. Frontiers in Pharmacology.
- Gabius HJ et al. (2020). Lectin–glycan interactions in lung remodeling. Histochem Cell Biol.
- Mishra et al. (2021). Sugar-based targeted delivery in fibrotic diseases. Bioconjug Chem.
- Beck et al., 2023. Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage, Nature Communications, Vol. 14, 4564.