Exposed collagen

Exposed collagen in the tumor stroma and neoangiogenic vasculature refers to collagen fibers, primarily Types I, III, and IV, that become accessible to circulating molecules due to the structural abnormalities of tumor blood vessels and the extensive remodeling of the extracellular matrix (ECM). In healthy tissues, collagen is typically masked by other ECM components or sequestered within intact basement membranes, making it largely invisible to circulating factors. However, in the tumor microenvironment, the leaky nature of neoangiogenic vessels and the degradation of the ECM by proteases like matrix metalloproteinases (MMPs) expose cryptic epitopes and denatured strands of collagen. This exposure makes it a highly attractive target for site-specific drug delivery, as therapeutic agents can be fused with collagen-binding domains (CBDs) to enhance their accumulation and retention within the tumor while minimizing systemic toxicity. Targeting exposed collagen has been explored for various modalities, including immunotherapies (e.g., CBD-cytokines, CBD-checkpoint inhibitors) and chemotherapeutics, to improve efficacy and safety profiles. Additionally, this target is utilized in imaging to visualize areas of active tissue remodeling and vascular damage.

Other names

Denatured collagenCryptic collagen epitopesUnfolded collagenTumor-associated collagenExposed collagen networkVascular collagen network

Targeting moieties such as collagen-binding domains (CBDs) or collagen hybridizing peptides (CHPs) selectively bind to exposed triple-helical surfaces or denatured strands of collagen revealed by pathological remodeling or leaky vasculature, facilitating localized delivery and prolonged retention of therapeutic or diagnostic agents.