Receptor-specific targeting with liposomes in vitro based on sterol-PEG(1300) anchors.
OBJECTIVE
The challenge in developing liposomes to be used in active drug targeting is to design a method that can be used for modifying liposomal membranes that is applicable for a number of different specific ligands. In this study, the post insertion technique was used with activated sterol-PEG(1300) anchors and was evaluated with regard to its effectiveness in active targeting in vitro. The key advantage of these anchors is that the insertion step into the liposomal membrane takes place at room temperature and is very fast.


METHODS
For in vitro experiments, neuroblastoma cell lines overexpressing GD2 antigen on their surface as a target structure were chosen. This allowed the use of anti-GD2 antibodies coupled to the liposomal surface for testing of specific binding. These modified liposomes were labelled with rhodamine-PE and their cellular association was analyzed by flow cytometry.


RESULTS
It was shown that the activated sterol-PEG(1300) anchors allow specific and significant interactions of the modified liposomes with GD2 positive cells.


CONCLUSIONS
Coupling using sterol-PEG(1300) anchors is both simple and rapid. It is reproducible and applicable for all ligands bearing amino groups. This method demonstrates the advantage of a ready-to-use system for the modification of pre-formed liposomes with different ligands.
Gantert
Markus
M
Department of Pharmaceutical Technology and Biopharmacy, Albert-Ludwigs University, Hermann-Herder-Str. 9, 79104, Freiburg, Germany.
Lewrick
Felicitas
F
Adrian
Joanna E
JE
Rössler
Jochen
J
Steenpass
Thomas
T
Schubert
Rolf
R
Peschka-Süss
Regine
R
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000737:chemistry*; D015394:Molecular Structure; D010840:Phytosterols / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D013388:Succinimides / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D008024:Ligands; D008081:Liposomes; D010840:Phytosterols; D013388:Succinimides; D013450:Sulfones; C032605:2,2,2-trifluoroethanesulfonyl chloride; D011092:Polyethylene Glycols; C019403:ganglioside, GD2; C001426:N-hydroxysuccinimide