Liposome for blocking site-specifically chemokine-related inflammatory processes in vascular diseases and metastasis

摘要

The invention provides a method for blocking site-specifically chemokine-related inflammatory processes in vascular diseases and metastasis employing vascular targeted nanocarrier. In particular, the present invention provides two types of targeted n ano c arrier (NC) with encapsulated c hemokine a ntagonists (CA) or c hemokine r eceptor a ntagonists (CRA): stabilised t arget-sensitive l iposomes (TSL) and p olymeric n anoparticles (PNP). Both types of nanocarrier have attached on their surface monoclonal antibodies or peptides that recognize VCAM-1 expressed on activated endothelial cells (EC). After binding of the nanocarrier to the VCAM-1 expressed on EC, the encapsulated CA or CRA are released and will block the interaction between chemokine and chemokine receptors. This will lead to an inhibition of transmigration of leukocytes (in atherosclerosis) or of tumor metastatic cells (in cancer). The invention provides a carrier system which delivers effective concentrations of drugs specifically to the diseased (target) sites and reduces the drug concentrations at non-target sites. This results in a reduced, even absent, occurrence of side effects. The nanocarriers described in this invention have the potential to function as long-lasting vehicles for delivering selectively CA or CRA to activated endothelium.