Mn. Jones et Mjh. Hudson, THE TARGETING OF IMMUNOLIPOSOMES TO TUMOR-CELLS (A431) AND THE EFFECTS OF ENCAPSULATED METHOTREXATE, Biochimica et biophysica acta, 1152(2), 1993, pp. 231-242
Immunoliposomes have been prepared from lipid mixtures of dipalmitoylp
hosphatidylcholine, wheat germ phosphatidylinositol and a reactive lip
id (the m-maleimidobenzoyl-N-hydroxysuccinimide derivative of dipalmit
oylphosphatidylethanolamine) which was conjugated to the N-succinimidy
l-S-acetylthioacetate (SATA) derivative of a monoclonal antibody (H17E
2) raised to human placental alkaline phosphatase (PLAP). The immunoli
posomes were prepared by the extrusion technique (VETs) and by reverse
phase evaporation (REVs) and were found to effectively target to immo
bilised PLAP and to PLAP or PLAP-like enzyme on the surface of a tumou
r cell line (A431) using an ELISA and autoradiography. The extent of b
inding to immobilised PLAP was a function of immunoliposomal lipid con
centration, the weight-average number of antibody molecules per liposo
me (P(w)BAR) and the liposome size. The effectiveness of methotrexate-
loaded immunoliposomes in inhibiting the proliferation of A431 cells w
as investigated relative to equivalent levels of the free drug. The im
munoliposomes prepared by the extrusion technique (VETs) inhibited gro
wth of A431 cells but had no effect on the growth of a normal human fi
broblastic cell line. Immunoliposomes prepared by reverse phase evapor
ation (REVs) were less effective in inhibiting A431 cell proliferation
. The immunoliposomes probably enter the tumour cells largely by recep
tor-mediated endocytosis although other mechanisms of uptake cannot be
excluded.