Targeted nanoparticle contrast agents for vascular molecular imaging and therapy

Samuel A. Wickline, Anne M. Neubauer, Patrick Winter, Shelton Caruthers, Gregory Lanza

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Over the next decade, the growth of nanotechnology platforms for molecular imaging and drug delivery will greatly expand the clinical opportunities for cardiovascular molecular imaging.9-11 Nanotechnology seeks to develop new materials and provide new molecular assemblies on the scale of individual cells or organelles in the range of 5-500 nm. One of the classic original nanoparticulate systems, liposomes (50-700 nm) are uni-or multilamellar vesicles comprising lipid bilayer membranes surrounding an aqueous interior. These agents have now been approved for enhancing the efficacy and safety of drugs such as doxorubicin (e.g. Doxil, ALZA Corporation, Tibotec Therapeutics, NJ). Applications of liposomal technology as molecular imaging agents have been reported for both ultrasound and magnetic resonance imaging (MRI).12,13 Nanometer-sized emulsions are chemically distinct from liposomes; they are selfassemble (as oil-in-water)-type mixtures that are stabilized with surfactants to maintain size and shape. Perfluorocarbon core emulsions (200-400 nm) have been used for molecular imaging with MRI, ultrasound, fluorescence, nuclear, and computed tomography (CT) imaging.9,11,14,15 For example, by incorporating vast numbers of paramagnetic gadolinium complexes (>50 000) onto emulsion particles, the signal enhancement possible for each binding site is magnified dramatically, by a factor of >106 over conventional paramagnetic extracellular contrast agents.16,17 Modified micellar particles such as highdensity lipoprotein (HDL) or low-density lipoprotein (LDL) particles have been utilized as molecular imaging agents for MRI.18,19 Polymer-based nanoparticles (40-200 nm) support a variety of flexible ‘designer approaches’ to the development of molecular imaging agents and therapeutic delivery devices.20 Polymers made from polyhydroxy acids such as the copolymer of poly (lactic acid) (PLA) and poly (D, L-lactide-co -glycolide) (PLGA) have been investigated for localized drug and gene delivery. Dendrimers, or cascade polymers, are highly branched polymeric structures that are globular in configuration. Paramagnetic polyamidoamine (PAMAM) and diaminobutane (DAB) dendrimers have been reported for MRI applications.21,22 The multivalent surfaces of these and other systems contain an array of functional sites that can undergo reactions to add drugs, imaging agents, and targeting ligands.

Original languageEnglish
Title of host publicationHandbook of the Vulnerable Plaque, Second Edition
PublisherCRC Press
Pages289-302
Number of pages14
ISBN (Electronic)9781439804537
ISBN (Print)184184621X, 9781841846217
StatePublished - Jan 1 2007

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    Wickline, S. A., Neubauer, A. M., Winter, P., Caruthers, S., & Lanza, G. (2007). Targeted nanoparticle contrast agents for vascular molecular imaging and therapy. In Handbook of the Vulnerable Plaque, Second Edition (pp. 289-302). CRC Press.