Development of EGF-conjugated liposomes for targeted delivery of boronated DNA-binding agents.
Liposomes are of interest as drug delivery tools for therapy of cancer and infectious diseases. We investigated conjugation of epidermal growth factor, EGF, to liposomes using the micelle-transfer method. EGF was conjugated to the distal end of PEG-DSPE lipid molecules in a micellar solution and the EGF-PEG-DSPE lipids were then transferred to preformed liposomes, either empty or containing the DNA-binding compound, water soluble acridine, WSA. We found that the optimal transfer conditions were a 1-h incubation at 60 degrees C. The final conjugate, (125)I-EGF-liposome-WSA, contained approximately 5 mol % PEG, 10-15 EGF molecules at the liposome surface, and 10(4) to 10(5) encapsulated WSA molecules could be loaded. The conjugate was shown to have EGF-receptor-specific cellular binding in cultured human glioma cells.
Division of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University. S- 751 85 Uppsala, Sweden.
Erika
E
Bohl Kullberg
Nill
N
Bergstrand
Jörgen
J
Carlsson
Katarina
K
Edwards
Markus
M
Johnsson
Stefan
S
Sjöberg
Lars
L
Gedda
D000166:Acridines / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D001896:Boron Compounds / Q000737:chemistry / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000627:therapeutic use; D005910:Glioma / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000627:therapeutic use; D008081:Liposomes / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use; D011869:Radioligand Assay; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D000166:Acridines; D001896:Boron Compounds; D007364:Intercalating Agents; D008081:Liposomes; D009363:Neoplasm Proteins; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor