Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents.
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.
Glickson
Jerry D
JD
Molecular Imaging Laboratory, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6069, USA. glickson@mail.med.upenn.edu
Lund-Katz
Sissel
S
Zhou
Rong
R
Choi
Hoon
H
Chen
I-Wei
IW
Li
Hui
H
Corbin
Ian
I
Popov
Anatoliy V
AV
Cao
Weiguo
W
Song
Liping
L
Qi
Chenze
C
Marotta
Diane
D
Nelson
David S
DS
Chen
Juan
J
Chance
Britton
B
Zheng
Gang
G
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
D002352:Carrier Proteins; D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; D008074:Lipoproteins; D010087:Oxides; D011956:Receptors, Cell Surface; D007501:Iron