title: Low-density lipoprotein nanoparticles as magnetic resonance imaging contrast agents.
abstract: Low-density lipoproteins (LDLs) are a naturally occurring endogenous nanoplatform in mammalian systems. These nanoparticles (22 nm) specifically transport cholesterol to cells expressing the LDL receptor (LDLR). Several tumors overexpress LDLRs presumably to provide cholesterol to sustain a high rate of membrane synthesis. Amphiphilic gadolinium (Gd)-diethylenetriaminepentaacetic acid chelates have been incorporated into the LDL to produce a novel LDLR-targeted magnetic resonance imaging (MRI) contrast agent. The number of Gd chelates per LDL particle ranged between 150 and 496 Gd(III). In vitro studies demonstrated that Gd-labeled LDL retained a similar diameter and surface charge as the native LDL particle. In addition, Gd-labeled LDL retained selective cellular binding and uptake through LDLR-mediated endocytosis. Finally, Gd-labeled LDLs exhibited significant contrast enhancement 24 hours after administration in nude mice with human hepatoblastoma G2 xenografts. Thus, Gd-labeled LDL demonstrates potential use as a targeted MRI contrast agent for in vivo tumor detection.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Corbin
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Sissel
authors.initials: S
authors.lastname: Lund-Katz
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Glickson
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D004705:Endocytosis; D005260:Female; D019786:Gadolinium DTPA / Q000494:pharmacology; D018197:Hepatoblastoma / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009368:Neoplasm Transplantation
chemical_list: D003287:Contrast Media; D008077:Lipoproteins, LDL; D019786:Gadolinium DTPA