Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo.
This paper deals with the utility of immunoliposomes for the delivery of doxorubicin (DXR) to human ovarian carcinoma cells in vitro and in vivo. We aimed to investigate whether immunoliposome-mediated targeting of DXR to ovarian cancer cells translates in an enhanced anti-tumour effect compared with that of non-targeted DXR liposomes (lacking the specific antibody). Target cell binding and anti-tumour activity of DXR immunoliposomes were studied in vitro and in vivo (xenograft model of ovarian carcinoma). In vitro we observed that target cell binding and cell growth inhibition of DXR immunoliposomes is superior to that of non-targeted DXR-liposomes. However, in vivo, despite the efficient target cell binding and good anti-tumour response of DXR-immunoliposomes, no difference in anti-tumour effect, compared with non-targeted DXR-liposomes, could be determined. The results indicate that premature DXR leakage from immunoliposomes occurring before the actual target cell binding and subsequent DXR association with the tumour cells, explains why no significant differences in anti-tumour activity between DXR-immunoliposomes and non-targeted DXR-liposomes were observed in vivo.
Vingerhoeds
M H
MH
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
Steerenberg
P A
PA
Hendriks
J J
JJ
Dekker
L C
LC
Van Hoesel
Q G
QG
Crommelin
D J
DJ
Storm
G
G
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin