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 visible or near-infrared fluorescent optical and magnetic resonance imaging (MRI) contrast agents and photodynamic therapy and chemotherapeutic agents to normal and neoplastic cells that overexpress low-density lipoprotein receptors (LDLRs). Extension to other lipoproteins ranging in diameter from about 10 nm (high-density lipoprotein [HDL]) to over a micron (chylomicrons) is feasible. Loading of contrast or therapeutic agents onto or into these particles has been achieved by protein loading (covalent attachment to protein side chains), surface loading (intercalation into the phospholipid monolayer), and core loading (extraction and reconstitution of the triglyceride/cholesterol ester core). Core and surface loading of LDL have been used for delivery of optical imaging agents to tumor cells in vivo and in culture. Surface loading was used for delivery of gadolinium-bis-stearylamide contrast agents for in vivo MRI detection in tumor-bearing mice. Chlorin and phthalocyanine near-infrared photodynamic therapy agents (< or = 400/LDL) have been attached by core loading. Protein loading was used to reroute the LDL from its natural receptor (LDLR) to folate receptors and could be used to target other receptors. A semisynthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles with carboxylated cholesterol and overlaying a monolayer of phospholipid to which apolipoprotein A1 or E was adsorbed for targeting HDL or adsorbing synthetic amphipathic helical peptides ltargeting LDL or folate receptors. These particles can be used for in situ loading of magnetite into cells for MRI-monitored cell tracking or gene expression.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA 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: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D005682:Gadolinium / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D011956:Receptors, Cell Surface / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D005682:Gadolinium