title: Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents.
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 approximately 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 ofphospholipid to which Apo A1, Apo E or synthetic amphoteric alpha-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.
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6069, USA. glickson@mail.med.upenn.edu
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Glickson
authors.forename: Sissel
authors.initials: S
authors.lastname: Lund-Katz
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Hoon
authors.initials: H
authors.lastname: Choi
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ian
authors.initials: I
authors.lastname: Corbin
authors.forename: Anatoliy V
authors.initials: AV
authors.lastname: Popov
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cao
authors.forename: Liping
authors.initials: L
authors.lastname: Song
authors.forename: Chenze
authors.initials: C
authors.lastname: Qi
authors.forename: Diane
authors.initials: D
authors.lastname: Marotta
authors.forename: David S
authors.initials: DS
authors.lastname: Nelson
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Britton
authors.initials: B
authors.lastname: Chance
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry* / Q000494:pharmacology*; D016503:Drug Delivery Systems; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007501:Iron / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry* / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D010087:Oxides / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; D008074:Lipoproteins; D010087:Oxides; D011956:Receptors, Cell Surface; D007501:Iron