title: Mechanistic study of IR-780 dye as a potential tumor targeting and drug delivery agent.
abstract: IR-780 iodide, a near-infrared fluorescent heptamethine dye, has been recently characterized to exhibit preferential accumulation property in the mitochondria of tumor cells. In this study, we investigated the possible mechanisms for its tumor selective activity and its potential as a drug delivery carrier. Results showed that the energy-dependent uptake of IR-780 iodide into the mitochondria of tumor cells was affected by glycolysis and plasma membrane potential. Moreover, OATP1B3 subtype of organic anion transporter peptides (OATPs) may play a dominant role in the transportation of IR-780 iodide into tumor cells, while cellular endocytosis, mitochondrial membrane potential and the ATP-binding cassette transporters did not show significant influence to its accumulation. We further evaluated the potential of IR-780 iodide as a drug delivery carrier by covalent conjugation of IR-780 with nitrogen mustard (IR-780NM). In vivo imaging showed that IR-780NM remained the tumor targeting property, indicating that IR-780 iodide could be potentially applied as a drug delivery agent for cancer targeted imaging and therapy.
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing 400038, China.
authors.forename: Erlong
authors.initials: E
authors.lastname: Zhang
authors.forename: Shenglin
authors.initials: S
authors.lastname: Luo
authors.forename: Xu
authors.initials: X
authors.lastname: Tan
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Shi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D004705:Endocytosis; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics*; D007454:Iodides / Q000737:chemistry / Q000493:pharmacokinetics*; D008466:Mechlorethamine / Q000737:chemistry / Q000493:pharmacokinetics; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D027361:Organic Anion Transporters / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D018528:ATP-Binding Cassette Transporters; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007211:Indoles; D007454:Iodides; D027361:Organic Anion Transporters; D008466:Mechlorethamine
keywords: Glycolysis; IR-780 iodide; Nitrogen mustard; OATP1B3; Plasma membrane potential