Radiation-guided targeting of combretastatin encapsulated immunoliposomes to mammary tumors.
OBJECTIVE
Radiation upregulates expression of endothelial cell adhesion molecules providing a potential avenue for targeting drugs to irradiated tissue. Induced upregulation of E-selectin can be used to target immunoliposomes to solid tumors. The effects of targeting immunoliposomes containing the antivascular drug combretastatin disodium phosphate (CA4P) to irradiated mammary tumors were investigated in this study.


METHODS
Mice bearing transplanted MCa-4 mouse mammary tumors were assigned to one of the factorial treatments permuting the administration of free CA4P, tumor irradiation, CA4P encapsulated liposomes, and CA4P encapsulated immunoliposomes (conjugated with anti-E-selectin). Single and fractionated dosing of radiation and/or CA4P was evaluated.


RESULTS
For single dose treatments the group that received a single dose of radiation plus a single dose of immunoliposomes showed a significant delay in tumor growth compared to all other treatment groups. Fractionated radiation plus fractionated doses of immunoliposomes resulted in further tumor growth delay; however, it was not significantly different from other fractionated dose treatment groups that combined radiation and CA4P.


CONCLUSIONS
Targeting of antivascular drugs to irradiated tumors via ligand-bearing liposomes results in significant tumor growth delay. This effect can be further potentiated using a fractionated irradiation dosing schedule combined with fractionated immunoliposome treatments.
Pattillo
Christopher B
CB
Department of Mechanical Engineering, Temple University, 1947 N. 12th St., Philadelphia, Pennsylvania 19122, USA.
Venegas
Berenice
B
Donelson
Fred J
FJ
Del Valle
Luis
L
Knight
Linda C
LC
Chong
Parkson L-G
PL
Kiani
Mohammad F
MF
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001632:Bibenzyls / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D016503:Drug Delivery Systems; D019040:E-Selectin / Q000235:genetics / Q000276:immunology*; D005260:Female; D008081:Liposomes / Q000276:immunology* / Q000493:pharmacokinetics; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011827:Radiation; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D019040:E-Selectin; D008081:Liposomes; C040105:combretastatin