Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery

Eliot. P. Botosoa,Patricia Remaud-Le Saëc,Jean-François Gestin,Alain Faivre-Chauvet,Mike Maillasson,Jacques Barbet,Yannick Jacques,Marie Mougin-Degraef

doi:10.1155/2011/368535

Abstract

Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex) and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR). Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy.

Highlights

The development of liposomes capable of targeting cells has been an objective since the 80s [1, 2]
Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety
This steric hindrance is observed when an antibody is attached to the liposomes surface [10] and, as shown in this paper, when the liposome is tagged with a small molecular weight ligand to be recognized by an antibody or, as described by Cao and Suresh [4], by a bispecific antibody

Summary

Introduction

The development of liposomes capable of targeting cells has been an objective since the 80s [1, 2]. The ability of immunotargeted liposomes to deliver high doses of drugs or radioactivity to tumor cells in vivo remains to be demonstrated, partly because it is difficult to include all necessary features, that is, long circulation times, stable drug encapsulation or radiolabeling with high activities, and efficient antibody targeting in the liposomes preparation [3]. Other antibody constructs, such as bispecific antibodies, provide an alternative way to target liposomes to cancer cells [4].

Methods

Results

Discussion

Conclusion