Subcellular trafficking of HPMA copolymer-Tat conjugates in human ovarian carcinoma cells.
One of the main obstacles to efficient intracellular delivery of therapeutic macromolecules is the barrier posed by the plasma membrane. In this study, the cell penetrating peptide Tat was conjugated to a synthetic macromolecule based on N-(2-hydroxypropyl)methacrylamide (HPMA) and its subcellular distribution in human ovarian carcinoma cell lines was studied. The Tat peptide mediated uptake resulted in cytoplasmic and nuclear localization and was found to be energy independent. Time and concentration studies verified the rapidity and dependence of the transport process on these parameters. Enhanced uptake of a polymer bound anticancer drug doxorubicin was also demonstrated. These results were corroborated independently by subcellular fractionation.
Nori
Aparna
A
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, 30 S 2000 E, Room 301, Salt Lake City, UT 84112, USA.
Jensen
Keith D
KD
Tijerina
Monica
M
Kopecková
Pavla
P
Kopecek
Jindrich
J
D002277:Carcinoma / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015696:Gene Products, tat / Q000378:metabolism*; D006801:Humans; D008689:Methacrylates / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D015696:Gene Products, tat; D008689:Methacrylates; C032802:hydroxypropyl methacrylate