Evaluation of intracellular trafficking and clearance from HeLa cells of doxorubicin-bound block copolymers.
New technologies are needed to deliver medicines safely and effectively. Polymeric nanoparticulate carriers are one such technology under investigation. We examined the intracellular trafficking of doxorubicin-bound block copolymers quantitatively and by imaging doxorubicin-derived fluorescence using confocal microscopy. The polymers were internalized by endocytosis and distributed in endosomal/lysosomal compartments and the endoplasmic reticulum; unlike free doxorubicin, the polymers were not found in the nucleus. Moreover, the ATP-binding cassette protein B1 (ABCB1) transporter may be involved in the efflux of the polymer from cells. This drug delivery system is attractive because the endogenous transport system is used for the uptake and delivery of the artificial drug carrier to the target as well as for its efflux from cells to medium. Our results show that a drug delivery system strategy targeting this endogenous transport pathway may be useful for affecting specific molecular targets.
Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Kumiko
K
Sakai-Kato
Keiko
K
Ishikura
Yuki
Y
Oshima
Minoru
M
Tada
Takuo
T
Suzuki
Akiko
A
Ishii-Watabe
Teruhide
T
Yamaguchi
Nobuhiro
N
Nishiyama
Kazunori
K
Kataoka
Toru
T
Kawanishi
Haruhiro
H
Okuda
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D008247:Lysosomes / Q000378:metabolism; D008823:Micelles; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D034622:RNA Interference; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D004317:Doxorubicin