Mr and fluorescent imaging of low-density lipoprotein receptors1

Li, Hui; Gray, Brian; Corbin, Ian R.; Lebherz, Corinna; Choi, Hoon; Lund‐Katz, Sissel; Wilson, James M.; Glickson, Jerry D.; Zhou, Rong

doi:10.1016/j.acra.2004.08.007

Cited by 68 publications

(51 citation statements)

References 43 publications

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“…LDL or HDL can be paramagnetically labeled (102,103) for identification of atherosclerotic plaques after uptake of these contrast agents by the plaque. All inflammatory markers, e.g.…”

Section: Atherosclerosismentioning

confidence: 99%

Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

et al. 2006

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In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles. A relatively new and promising application of lipidic nanoparticles is their use as multimodal MR contrast agents. Lipids are amphiphilic molecules with both a hydrophobic and a hydrophilic part, which spontaneously assemble into aggregates in an aqueous environment. In these aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster together and the hydrophilic parts face the water. In the low concentration regime, a wide variety of structures can be formed, ranging from spherical micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum dots or perfluorocarbon emulsions can be solubilized using this approach. MR-detectable and fluorescent amphiphilic molecules can easily be incorporated in lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to lipidic particles by incorporating lipids with a functional moiety to allow a specific interaction with molecular markers and to achieve accumulation of the particles at disease sites. In this review, an overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd-based contrast agents. The mechanisms of particle formation, conjugation strategies and applications in the field of contrast-enhanced, cellular and molecular MRI are discussed.

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“…LDL or HDL can be paramagnetically labeled (102,103) for identification of atherosclerotic plaques after uptake of these contrast agents by the plaque. All inflammatory markers, e.g.…”

Section: Atherosclerosismentioning

confidence: 99%

Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

et al. 2006

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“…55; I. Corbin, H.L., J.C., J.D.G., and G.Z., unpublished data). Bifunctional Gd chelates containing f luorescent dyes that facilitate in vitro tracking by confocal microscopy have also been developed (55). A major limitation to such agents is the limited number of Gd chelates that can be attached to the phospholipid monolayer; thus, the relaxation enhancement provided by these agents is limited.…”

Section: Mechanism Underlying Selective Alkylation Of Lys -Amino Groupsmentioning

confidence: 99%

Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents

Zheng

Chen²,

Li³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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201

186

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We report that a lipoprotein-based nanoplatform generated by conjugating tumor-homing molecules to the protein components of naturally occurring lipoproteins reroutes them from their normal lipoprotein receptors to other selected cancer-associated receptors. Multiple copies of these targeting moieties may be attached to the same nanoparticle, or a variety of different targeting moieties can be attached. Such a diverse set of tumor-homing molecules could be used to create a variety of conjugated lipoproteins as multifunctional, biocompatible nanoplatforms with a broad application to both cancer imaging and treatment. The same principle can be applied to imaging and treatment of other diseases and for monitoring specific tissues. To validate this concept, we prepared a low-density lipoprotein (LDL)-based folate receptor (FR)-targeted agent by conjugating folic acid to the Lys residues of the apolipoprotein B (apoB)-100 protein. To demonstrate the ability of the lipoprotein-based nanoplatform to deliver surfaceloaded and core-loaded payloads, the particles were labeled either with the optical reporter 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine that was intercalated in the phospholipid monolayer or with the lipophilic photodynamic therapy agent, tetra-tbutyl-silicon phthalocyanine bisoleate, that was reconstituted into the lipid core. Cellular localization of the labeled LDL was monitored by confocal microscopy and flow cytometry in FR-overexpressing KB cells, in FR-nonexpressing CHO and HT-1080 cells, and in LDL receptor-overexpressing HepG 2 cells. These studies demonstrate that the folic acid conjugation to the Lys side-chain amino groups blocks binding to the normal LDL receptor and reroutes the resulting conjugate to cancer cells through their FRs.folate receptor ͉ low-density lipoprotein receptor ͉ biocompatible ͉ optical imaging ͉ photodynamic therapy

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“…The prototype amphiphilic contrast agent (PTIR267) was the first in this series; it contained both a fluorophore and a Gd(III) moiety along with two palmitate hydrocarbon chains to facilitate intercalation into the LDL phospholipid monolayer (Fig. 18.10) [78]. Approximately 50 molecules of PTIR267 can be attached to each LDL macromolecule.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

“…Intravenous administration of this agent into a B16 tumor bearing mouse demonstrated that the labeled LDL accumulated within the liver and tumor (Fig. 18.10) [78]. However, the bulky nature of the PTIR267 complex limits the number of probes that can be loaded onto the LDL surface (upper limit of 50).…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Lipoprotein‐Based Nanoplatforms for Cancer Molecular Imaging

Corbin

Zheng

2011

Nanoplatform‐Based Molecular Imaging

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LIPOPROTEINS: NATURE'S ENDOGENOUS NANOCARRIEREfficient transport of key lipids, such as triacylglycerols (TAGs) and cholesterol, is an essential process in mammalian systems. These molecules respectively serve as a high-energy fuel source and as a structural building block for all cells. Like other essential nutrients and substrates these molecules must be delivered to cells through the blood. The hydrophobicity of these molecules, however, poses a daunting problem for their transport through the aqueous channels of the vascular system. Nature has uniquely addressed this dilemma through the lipoprotein carrier system. Plasma lipoproteins are macromolecular vehicles that transport neutral lipids (fat and cholesterol) through the circulatory system and extracellular fluid compartments of the body. These spherical emulsion-like complexes display a range of physicochemical properties; however, they have a common structural organization ( Fig. 18.1.) consisting of an apolar core of TAG and cholesterol esters surrounded by a monolayer of phospholipids and free cholesterol. Interspersed across the phospholipid monolayer are specific amphipathic proteins (apolipoproteins) whose hydrophilic domains extend toward the aqueous environment. These apolipoproteins act to stabilize and confer structural framework to the lipoproteins, modulate enzyme activity, as well as serve as receptor ligands for the lipoprotein delivery system [1]. Nanoplatform-Based Molecular Imaging Edited by Xiaoyuan ChenPlasma lipoproteins can be designated into various classes based on numerous physical parameters (e.g., electrophoretic mobility, diameter). The most commonly accepted classification is based on the density of the different lipoprotein species (see Table 18.1). According to this classification scheme the major density categories include the following.(1) Chylomicrons (d < 0.95 g/mL) are TAG-rich emulsions particles (80-88% by weight) that are synthesized by the intestine after a fatty meal. Chylomicrons are the largest particles in the lipoprotein family (80 nm to 1 m in diameter) and have the highest lipid-to-protein ratio.(2) Very low density lipoproteins (d = 0.95-1.006 g/mL) are also TAG-rich particles, however, they are synthesized by the liver. They are smaller than chylomicrons (30-80 nm in diameter) and contain relatively less TAG but more cholesterol and protein.(3) Low density lipoproteins (d = 1.020-1.063 g/mL) are particles formed from the intravascular catabolism of VLDLs. The LDL core is predominantly cholesterol ester molecules. Finally, (4) high density lipoproteins (d = 1.063-1.210 g/mL) These carriers are the smallest (6-12 nm in diameter) member of the lipoprotein family. Their core is mainly composed of cholesterol esters and they are composed of a relatively high proportion of protein (35-56% by weight).

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Mr and fluorescent imaging of low-density lipoprotein receptors1

Cited by 68 publications

References 43 publications

Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents

Lipoprotein‐Based Nanoplatforms for Cancer Molecular Imaging

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