title: Intracellular trafficking considerations in the development of natural ligand-drug molecular conjugates for cancer.
abstract: Overexpressed receptors, characteristic of many cancers, have been targeted by various researchers to achieve a more specific treatment for cancer. A common approach is to use the natural ligand for the overexpressed receptor as a cancer-targeting agent which can deliver a chemically or genetically conjugated toxic molecule. However, it has been found that the therapeutic efficacy of such ligand-drug molecular conjugates can be limited, since they naturally follow the intracellular trafficking pathways of the endogenous ligands. Therefore, a thorough understanding of the intracellular trafficking properties of these ligands can lead to novel design criteria for engineering ligands to be more effective drug carriers. This review presents a few commonly used ligand/receptor systems where intracellular trafficking considerations can potentially improve the therapeutic efficacy of the ligand-drug molecular conjugates.
authors.affiliation: Department of Bioengineering, University of California-Los Angeles, CA 90095, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Yoon
authors.forename: Christina T
authors.initials: CT
authors.lastname: Liu
authors.forename: Devin S
authors.initials: DS
authors.lastname: Quinlan
authors.forename: Parsa M
authors.initials: PM
authors.lastname: Nafisi
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Kamei
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D001698:Biomedical Engineering; D004167:Diphtheria Toxin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005098:Exotoxins / Q000008:administration & dosage; D005492:Folic Acid / Q000008:administration & dosage; D058972:Folic Acid Transporters / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000008:administration & dosage; D008024:Ligands; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D053660:Receptors, Interleukin-13 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D012276:Ricin / Q000008:administration & dosage; D015398:Signal Transduction; D014168:Transferrin / Q000008:administration & dosage / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D004337:Drug Carriers; D005098:Exotoxins; D058972:Folic Acid Transporters; D018793:Interleukin-13; D008024:Ligands; D053660:Receptors, Interleukin-13; D011990:Receptors, Transferrin; D014168:Transferrin; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D004317:Doxorubicin; D012276:Ricin; D005492:Folic Acid; D066246:ErbB Receptors