Tricarbocyanine cholesteryl laurates labeled LDL: new near infrared fluorescent probes (NIRFs) for monitoring tumors and gene therapy of familial hypercholesterolemia

Zheng G, Li H, Yang K, Blessington D, Licha K, Lund-Katz S, Chance B, Glickson JD

Bioorganic & medicinal chemistry letters, 2002

DOI: 10.1016/s0960-894x(02)00193-2

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 G₂ (HepG₂), confirmed that this NIRF were internalized selectively by the tumor and detected with high sensitivity by a low-temperature 3-D redox scanner. The synthesis and selective internalization of a new NIRF by HepG₂ tumor overexpressing LDL receptors are reported.