title: Endocytosis and intracellular trafficking properties of transferrin-conjugated block copolypeptide vesicles.
abstract: Block polypeptides are an emerging class of materials that have the potential to be used in many biomedical applications, including the field of drug delivery. We have previously developed a negatively charged block copolypeptide, poly(L-glutamate)60-b-poly(L-leucine)20 (E60L20), which forms spherical vesicles in aqueous solution. Since these vesicles are negatively charged, they are minimally toxic toward cells. However, the negative charge also inhibits these vesicles from effectively being internalized by cells, which can be problematic as many therapeutics have intracellular targets. To overcome this limitation of the E60L20 vesicles, transferrin (Tf) was conjugated onto the vesicle surface, since the receptor for Tf is overexpressed on cancer cells. The enhanced uptake of the Tf-conjugated vesicle was verified through confocal microscopy. Furthermore, endocytosis and immunostaining experiments confirmed that the Tf conjugated on the vesicle surface plays a critical role in the internalization and subsequent intracellular trafficking behavior of the vesicles.
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, California 90095, United States.
authors.forename: Uh-Joo
authors.initials: UJ
authors.lastname: Choe
authors.forename: April R
authors.initials: AR
authors.lastname: Rodriguez
authors.forename: Brian S
authors.initials: BS
authors.lastname: Lee
authors.forename: Scott M
authors.initials: SM
authors.lastname: Knowles
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Deming
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Kamei
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D055672:Static Electricity; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism; D014867:Water
chemical_list: D004337:Drug Carriers; D010455:Peptides; D011990:Receptors, Transferrin; D014168:Transferrin; D014867:Water; C027819:polyleucine; D011099:Polyglutamic Acid