BEH. 462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 17: Drug targeting Last time Intracellular drug de Today Drug targeting Reading T.J. Wickham, 'Ligand-directed targeting of genes to the site of disease, Nat. Med. 9(1) 135-139(2003) Drug Targeting Applications of drug targeting delivery of toxic drugs to tumors o highly toxic drugs that are too dangerous to deliver in a systemic manner e.g. potent radionuclides, cellular toxins allow smaller doses to be used delivery of DNa vectors to target cell type for genetic corrections targeting to vasculature o cancer treatment target to neovasculature forming around tumors on pulmonary, cardiovascular, and inflammatory diseases targeting to pathogen-infected cells od infected cells undergo changes in cell-surface molecule expression crossing blood-brain barrier Application Cellular target Molecular target Targeting ligand igand type Anti-cancer therapy Various tumor cells Folate receptor Folate Protein ligand for target EGF EGF receptor preferentially expressed on target Neovascular tissue B-FN(fibronectin anti-B-FN antibody antibody against fibronectin isoform only expressed during embryonic development nd in aggressive an tumors Anti-cancer Endothelial cells E-selectin receptor expressed at therapy, pulmonary P-selectin recepto sites of inflammation cardiovascular, and inflammatory Anti-cancer therapy Transformed B CD20 Anti-CD20 antibody Antibody against target (leukemias and B lymphocytes cell-surface protein cell lymphomas unique to target class of Anti-cancer therapy Transformed T IL-2Ra(interleukin-2 Anti-IL-2Ra antibody Antibody against target (T cell lymphomas) lymphocytes receptor a chain cell-surface protein not expressed on normal resting cells Lecture 17-Drug targeting 1 of 7BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 17: Drug targeting Last time: Intracellular drug delivery Today: Drug targeting Reading: T.J. Wickham, ‘Ligand-directed targeting of genes to the site of disease,’ Nat. Med. 9(1) 135-139 (2003) Drug Targeting Applications of drug targeting1 ƒ delivery of toxic drugs to tumors o highly toxic drugs that are too dangerous to deliver in a systemic manner ƒ e.g. potent radionuclides, cellular toxins ƒ allow smaller doses to be used ƒ delivery of DNA vectors to target cell type for genetic corrections ƒ targeting to vasculature o cancer treatment ƒ target to neovasculature forming around tumors2 o pulmonary, cardiovascular, and inflammatory diseases ƒ targeting to pathogen-infected cells o infected cells undergo changes in cell-surface molecule expression ƒ crossing blood-brain barrier3 Application Cellular target Molecular target Targeting ligand Ligand type Anti-cancer therapy Various tumor cells Folate receptor EGF receptor Folate EGF Protein ligand for target receptor preferentially expressed on target cells Neovascular tissue B-FN (fibronectin isoform) anti-B-FN antibody antibody against fibronectin isoform only expressed during embryonic development and in aggressive tumors Anti-cancer Endothelial cells E-selectin sialyl LewisX receptor expressed at therapy, pulmonary, P-selectin receptor sites of inflammation cardiovascular, and inflammatory diseases Anti-cancer therapy Transformed B CD20 Anti-CD20 antibody Antibody against target (leukemias and B lymphocytes cell-surface protein cell lymphomas) unique to target class of cells (e.g. B cells) Anti-cancer therapy (T cell lymphomas) Transformed T lymphocytes IL-2Rα (interleukin-2 receptor a chain Anti-IL-2Rα antibody Antibody against target cell-surface protein not expressed on normal resting cells Lecture 17 – Drug targeting 1 of 7