Tissue-specific targeting based on markers expressed outside endothelial cells.

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Pharmacology

Background:

• Vascular targeting of endothelial cells is clinically applied but often insufficient for sustained therapeutic effects.
• Targeting non-endothelial cells within tissues is essential for long-term efficacy in disease management.
• Systemic agents can access perivascular, stromal, and parenchymal cells through vascular permeability.

Purpose of the Study:

• To overview progress in understanding targetable molecular markers outside the endothelium.
• To discuss challenges in identifying and characterizing non-endothelial proteins accessible to circulation.
• To explore novel strategies for selective drug and imaging agent delivery to pathological sites.

Main Methods:

• Review of accumulating evidence on molecular markers in normal development and pathology.
• Analysis of cell surface receptor interactions between circulating agents and tissue cells.
• Discussion of protein expression in endothelial and non-endothelial cells within specific tissues.

Main Results:

• Non-endothelial molecular markers accessible to systemically administered agents represent viable therapeutic and diagnostic targets.
• Vascular permeability allows agents to reach cells underlying the endothelium and interstitial extracellular matrix.
• Some proteins mark both endothelial and non-endothelial cells, potentially enhancing agent accumulation and retention in target tissues.

Conclusions:

• Targeting non-endothelial cells offers a promising approach for enhanced disease treatment and diagnostics.
• Further research is needed to establish the clinical relevance of deep tissue markers in disease-specific contexts.
• Overcoming challenges in identifying and characterizing these markers is crucial for advancing targeted therapies.