Low-density lipoprotein nanoparticles as magnetic resonance imaging contrast agents

Ian R. Corbin, Hui Li, Juan Chen, Sissel Lund-Katzy, Rong Zhou, Jerry D. Glickson, Gang Zheng

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

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)-diethylenetriamine pentaacetic 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 Gdlabeled 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.

Original languageEnglish (US)
Pages (from-to)488-498
Number of pages11
JournalNeoplasia
Volume8
Issue number6
DOIs
StatePublished - 2006

Keywords

  • Human hepatoblastoma G (HepG)
  • Low-density lipoprotein (LDL)
  • Low-density lipoprotein receptor
  • Magnetic resonance imaging (MRI)
  • Nanoparticle

ASJC Scopus subject areas

  • Cancer Research

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