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Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents

  • Jerry D. Glickson
  • Sissel Lund-Katz
  • Rong Zhou
  • Hoon Choi
  • I-Wei Chen
  • Hui Li
  • Ian Corbin
  • Anatoliy V. Popov
  • Weiguo Cao
  • Liping Song
  • Chenze Qi
  • Diane Marotta
  • David S. Nelson
  • Juan Chen
  • Britton Chance
  • Gang Zheng
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 645)

Abstract

Low-density lipoprotein (LDL) provides a highly versatile natural nanoplatform for delivery of optical and MRI contrast agents, photodynamic therapy agents and chemotherapeutic agents to normal and neoplastic cells that over express LDL receptors (LDLR). Extension to other lipoproteins ranging in diameter from ~5-10 nm (high density lipoprotein, HDL) to over a micron (chilomicrons) is feasible. Loading of contrast or therapeutic agents has been achieved by covalent attachment to protein side chains, intercalation into the phospholipid monolayer and extraction and reconstitution of the triglyceride/cholesterol ester core. Covalent attachment of folate to the lysine side chain amino groups was used to reroute the LDL from its natural receptor (LDLR) to folate receptors and could be utilized to target other receptors. A semi-synthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles (MIONs) with carboxylated cholesterol and overlaying a monolayer of phospholipid to which Apo A1, Apo E or synthetic amphoteric 〈-helical polypeptides were adsorbed for targeting HDL, LDL or folate receptors, respectively. These particles can be utilized for in situloading of magnetite into cells for MRI monitored cell tracking or gene therapy.

Keywords

HepG2 Hepatoma Cationic Amino Acid Cholesteryl Oleate Lysine Side Chain Phospholipid Monolayer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jerry D. Glickson
    • 1
  • Sissel Lund-Katz
    • 1
  • Rong Zhou
    • 1
  • Hoon Choi
    • 1
  • I-Wei Chen
    • 1
  • Hui Li
    • 1
  • Ian Corbin
    • 1
  • Anatoliy V. Popov
    • 1
  • Weiguo Cao
    • 1
  • Liping Song
    • 1
  • Chenze Qi
    • 1
  • Diane Marotta
    • 1
  • David S. Nelson
    • 1
  • Juan Chen
    • 1
  • Britton Chance
    • 1
  • Gang Zheng
    • 1
  1. 1.University of PennsylvaniaPhiladelphia

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