Tricarbocyanine cholesteryl laurates labeled LDL: new near infrared fluorescent probes (NIRFs) for monitoring tumors and gene therapy of familial hypercholesterolemia.
For monitoring low-density lipoprotein receptors (LDLr) in tumors and in livers of patients with familial hypercholesterolemia (FH) treated with gene therapy, a series of tricarbocyanine cholesteryl laurates were synthesized with the cholesteryl laurate moiety serving as the lipid-chelating anchor for low-density lipoprotein (LDL). One of these conjugates, TCL17, was successfully used to label LDL to give a new NIRF, TCL17-LDL. Ex vivo biological studies on an LDLr overexpressing tumor model, human hepatoblastoma G(2) (HepG(2)), confirmed that this NIRF were internalized selectively by the tumor and detected with high sensitivity by a low-temperature 3-D redox scanner.
Zheng
Gang
G
Department of Radiology, University of Pennsylvania, Philadelphia 19104, USA. zheng@rad.upenn.edu
Li
Hui
H
Yang
Kathy
K
Blessington
Dana
D
Licha
Kai
K
Lund-Katz
Sissel
S
Chance
Britton
B
Glickson
Jerry D
JD
D000818:Animals; D002232:Carbocyanines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D002788:Cholesterol Esters / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D008078:Cholesterol, LDL / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D015316:Genetic Therapy; D018197:Hepatoblastoma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism* / Q000628:therapy; D021621:Imaging, Three-Dimensional; D007848:Laurates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000378:metabolism* / Q000628:therapy; D051379:Mice; D011973:Receptors, LDL / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared
D002232:Carbocyanines; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D005456:Fluorescent Dyes; D007848:Laurates; D011973:Receptors, LDL