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Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents

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Oxygen Transport to Tissue XXX

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.

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Glickson, J.D. et al. (2009). Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents. In: Liss, P., Hansell, P., Bruley, D.F., Harrison, D.K. (eds) Oxygen Transport to Tissue XXX. Advances in Experimental Medicine and Biology, vol 645. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-85998-9_35

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