text: The ligand chosen for the application depends on the target site selected and it is responsible for cellular interaction. The target site contains the binding sites that the ligands target to deliver the LTL to the desired area. Favorable target site characteristics are determined by what is commonly expressed by tissues of the pathology of interest. Determinants can include histones, basement membrane fibrinogen, selectins, adhesion molecules, or other ligand targets. For example, in some human cancer tumors such as ovarian carcinomas, folate is over-expressed. Ligand-targeted liposomes for targeting cancer often use this over-expression of folate and a ligand that targets this vitamin to localize drug delivery to the desired area. Ligand-targeted liposomes utilize active targeting to interact with the desired cells.
  Once administered intravenously into blood circulation, ligand-targeted liposomes must travel to reach the target area to deliver their contents. LTLs retain the contained agent until the process of cellular uptake. LTLs are taken into cells through the process of receptor-mediated endocytosis. The ligand chosen for each application also depends on the target site selected. The target site contains the binding sites that the ligands target to deliver the LTL to the desired area. In some human tumors such as ovarian carcinomas, folate is over-expressed. Ligand-targeted liposomes for use in this application use this over-expression to folate and a ligand that targets folate to localize drug delivery to the desired area. The tumor microenvironment of solid tumor cancers is also a unique targeting site. Tumor endothelial cells are important for angiogenesis which is key to tumor growth, therefore using LTLs to target these cells can limit the growth and vascularization of a tumor.
  Receptor-mediated endocytosis is the most common way LTLs deliver material to the cell. The targeting ligand attached to the liposome attaches to the binding site found on the cell of interest. The particles are transported to lysosomes to be processed. This process allows the molecules to cross the blood-brain barrier, which allows the drug to be delivered to tissue that is relatively difficult to reach without a specific mechanism. Less commonly, pinocytosis or phagocytosis may be used for cellular uptake of the liposome. Certain recognition sites, such as ecto-NAD+oglycohydro|ase, mediate uptake to aid in the internalization and effectiveness of the LTLs.
  The remainder of LTLs in circulation after binding to the target site are mainly cleared through the reticuloendothelial system (RES). The RES includes different organs including the kidneys, lungs, spleen, liver, bone marrow, and lymph nodes. The liver is the primary organ for the clearance of LTLs. The RES is most likely able to clear LTLS due to fenestrations in their microvasculature that allow for extravasation. Phagocytic cells within the RES break down LTLs.