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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

21 Scopus citations

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 α-helical polypeptides were adsorbed for targeting HDL, LDL or folate receptors, respectively. These particles can be utilized for in situ loading of magnetite into cells for MRI monitored cell tracking or gene therapy.

Original languageEnglish (US)
Title of host publicationOxygen Transport to Tissue XXX
EditorsPer Liss, Peter Hansell, Duane Bruley, David Harrison
Pages227-239
Number of pages13
DOIs
StatePublished - 2009

Publication series

NameAdvances in Experimental Medicine and Biology
Volume645
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Glickson, J. D., Lund-Katz, S., Zhou, R., Choi, H., Chen, I. W., Li, H., Corbin, I., Popov, A. V., Cao, W., Song, L., Qi, C., Marotta, D., Nelson, D. S., Chen, J., Chance, B., & Zheng, G. (2009). Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents. In P. Liss, P. Hansell, D. Bruley, & D. Harrison (Eds.), Oxygen Transport to Tissue XXX (pp. 227-239). (Advances in Experimental Medicine and Biology; Vol. 645). https://doi.org/10.1007/978-0-387-85998-9_35