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  • Vascular Targeting of Radiolabeled Liposomes with Bio-Orthogonally Conjugated Ligands: Single Chain Fragments Provide Higher Specificity than Antibodies.

Vascular Targeting of Radiolabeled Liposomes with Bio-Orthogonally Conjugated Ligands: Single Chain Fragments Provide Higher Specificity than Antibodies.

Bioconjugate chemistry (2018-09-22)
Elizabeth D Hood, Colin F Greineder, Tea Shuvaeva, Landis Walsh, Carlos H Villa, Vladimir R Muzykantov
ABSTRACT

Liposomes are a proven, versatile, and clinically viable technology platform for vascular delivery of drugs and imaging probes. Although targeted liposomes have the potential to advance these applications, complex formulations and the need for optimal affinity ligands and conjugation strategies challenge their translation. Herein, we employed copper-free click chemistry functionalized liposomes to target platelet-endothelial cell adhesion molecule (PECAM-1) and intracellular adhesion molecule (ICAM-1) by conjugating clickable monoclonal antibodies (Ab) or their single chain variable fragments (scFv). For direct, quantitative tracing, liposomes were surface chelated with 111In to a >90% radiochemical yield and purity. Particle size and distribution, stability, ligand surface density, and specific binding to target cells were characterized in vitro. Biodistribution of liposomes after IV injection was characterized in mice using isotope detection in organs and by noninvasive imaging (single-photon emission computed tomography/computed tomography, SPECT/CT). As much as 20-25% of injected dose of liposomes carrying PECAM and ICAM ligands, but not control IgG accumulated in the pulmonary vasculature. The immunospecificity of pulmonary targeting of scFv/liposomes to PECAM-1 and ICAM-1, respectively, was 10-fold and 2.5-fold higher than of Ab/liposomes. Therefore, the combination of optimal ligands, benign conjugation, and labeling yields liposomal formulations that may be used for highly effective and specific vascular targeting.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
NanoFabTx - Azide Lipid Mix, for synthesis of azide-functionalized liposomes
Avanti
DSPE-PEG(2000) Azide, Avanti Research - A Croda Brand 880228C
Avanti
DSPE-PEG(2000) Azide, Avanti Research - A Croda Brand, powder
Avanti
16:0 PC (DPPC), Avanti Research - A Croda Brand
Avanti
DSPE-PEG(2000) Amine, Avanti Research - A Croda Brand 880128C
Avanti
DSPE-PEG(2000) Amine, Avanti Research - A Croda Brand
Avanti
16:0 PC (DPPC), Avanti Research - A Croda Brand
Avanti
Cholesterol (ovine), Avanti Research - A Croda Brand