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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.

Botosoa EP, Maillasson M, Mougin-Degraef M, Remaud-Le Saëc P, Gestin JF, Jacques Y, Barbet J, Faivre-Chauvet A - J Drug Deliv (2011)

Bottom Line: Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not.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.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Université de Nantes, Inserm, UMR 892, Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.

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.

No MeSH data available.


Related in: MedlinePlus

MAb 734 binding with DTPA-indium hapten. Inhibition of DTPA-111Indium binding to biotinylated MAb734 coated to avidin tubes as a function of DTPA-indium or EDTA-indium concentration. The equilibrium affinity constants were calculated from the data using standard Scatchard analysis.
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Related In: Results  -  Collection


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fig1: MAb 734 binding with DTPA-indium hapten. Inhibition of DTPA-111Indium binding to biotinylated MAb734 coated to avidin tubes as a function of DTPA-indium or EDTA-indium concentration. The equilibrium affinity constants were calculated from the data using standard Scatchard analysis.

Mentions: The MAb 734 was originally screened for its binding to soluble DTPA-indium complex [19]. Competition experiments (Figure 1) using tubes coated with MAb 734 allowed the equilibrium dissociation constant to be determined as 0.3 nM at 4°C.


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.

Botosoa EP, Maillasson M, Mougin-Degraef M, Remaud-Le Saëc P, Gestin JF, Jacques Y, Barbet J, Faivre-Chauvet A - J Drug Deliv (2011)

MAb 734 binding with DTPA-indium hapten. Inhibition of DTPA-111Indium binding to biotinylated MAb734 coated to avidin tubes as a function of DTPA-indium or EDTA-indium concentration. The equilibrium affinity constants were calculated from the data using standard Scatchard analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066559&req=5

fig1: MAb 734 binding with DTPA-indium hapten. Inhibition of DTPA-111Indium binding to biotinylated MAb734 coated to avidin tubes as a function of DTPA-indium or EDTA-indium concentration. The equilibrium affinity constants were calculated from the data using standard Scatchard analysis.
Mentions: The MAb 734 was originally screened for its binding to soluble DTPA-indium complex [19]. Competition experiments (Figure 1) using tubes coated with MAb 734 allowed the equilibrium dissociation constant to be determined as 0.3 nM at 4°C.

Bottom Line: Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not.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.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Université de Nantes, Inserm, UMR 892, Institut de Recherche Thérapeutique de l'Université de Nantes, 8 quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.

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.

No MeSH data available.


Related in: MedlinePlus