Ultrasound contrast agents targeted to malignancies: optimizing cellular attachment

Oum, Kelleny; Vega, Juan Luis Rodríguez; Leodore, L.M.; Forsberg, Flemming; Liu, J.B.; Merton, Daniel A.; Wheatley, Margaret A.

doi:10.1109/nebc.2005.1431989

Cited by 1 publication

(1 citation statement)

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“…We prepare functionalized PLA UCAs using a modified double emulsion solvent evaporation technique (Oum, 2004) by directly incorporating a mixture of phospholipids stored in chloroform into the oil phase of the emulsion (Duncanson et al, 2007). The phospholipids are used in a heterogeneous population of spheres (whole and dimpled), and shells.…”

Section: Methodsmentioning

confidence: 99%

Targeted binding of PEG‐lipid modified polymer ultrasound contrast agents with tiered surface architecture

Duncanson

Oum

Eisenbrey

et al. 2010

Biotech & Bioengineering

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In order for site-directed polymer ultrasound contrast agents (UCAs) to provide acoustic enhancement at disease sites to distinguish normal tissue from diseased tissue, the surface of these agents must be functionalized with mixtures of graftedpolymers. Here a combination of longer liganded polyethylene glycol (PEG)-lipids and shorter unliganded PEG-lipids were introduced into the oil phase of a modified solvent evaporation double emulsion method for preparing UCAs. UCAs with different lengths of both liganded and unliganded lipids were imaged under 7.5 MHz ultrasound. The B-mode image brightness of the mixed PEG-lipid UCAs was within 1 dB the brightness of the unliganded surface. After 15 min of continuous insonation, 70% of the contrast signal remained. The peptide Arginine-Glycine-Aspartic Acid (RGD) was added to the surface of these UCAs through a biotin-avidin linkage and binding was assessed under static and shear conditions. Binding was significant after 30 min of static incubation and the adherence of the UCA increased under shear flow from 3 UCA/cell (static) to 5 UCA/cell (shear). KeywordsUltrasound contrast agent; Polymer; Binding; In vitro; PEG-lipid Targeting ultrasound contrast agents (UCAs) to specific areas of disease through sitespecific ligand receptor binding has the potential to enhance the ability to delineate diseased tissue from healthy tissue (Bloch et al. 2004;Hughes et al. 2003;Klibanov 2005). A targeted contrast agent should be mechanically stable enough to transit the circulation for 30-60 min to survive multiple passes through the circulatory system as only a small amount of agent will pass through the binding site in one pass (Ferrara et al. 2007). Consequently, the targeted contrast agent accumulates at the binding site and increases signal intensity at the site for the duration of the imaging exam (Ophir and Parker 1989).In general, UCAs are small (<8 μm), shell-stabilized, intravenously injectable microbubbles (McCulloch et al. 2000) Polymers are well-suited for targeted UCAs as their shells are more durable than lipid or protein shells (Chen et al. 2003;Ferrara et al. 2007;Raisinghani and DeMaria 2002). Polylactic acid (PLA), a biocompatible and biodegradable polymer, has been suggested as a shell material as it is an FDA approved polymer for alternative uses and has gained widespread use in biomedical applications (Albertsson 2002;Arshady 1990 Thus, the purpose of this study is to employ the versatile lipid incorporation strategy to functionalize a PLA UCA with tiered surface architecture to achieve binding under shear flow conditions. Here, we extend our mixed phospholipid incorporation studies (Duncanson et al. 2007) with PLA microspheres to double emulsion PLA UCAs and assess their performance as UCAs. Furthermore, we coat the PLA UCA's surface using biotin-avidin bridging to RGD and quantify binding to cells under both static and shear flow conditions. Materials and MethodsWe prepare functionalized PLA UCAs using a modified double emulsion solvent evaporation techni...

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Section: Methodsmentioning

confidence: 99%