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...

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Bibliographic Details
Published in:Biomaterials 2014-01, Vol.35 (2), p.771-778
Main Authors: Zhang, Erlong, Luo, Shenglin, Tan, Xu, Shi, Chunmeng
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
ATP-Binding Cassette Transporters - metabolism
Cell Line, Tumor
Cell Membrane - metabolism
Dentistry
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Endocytosis
Flow Cytometry
Fluorescent Dyes - chemistry
Fluorescent Dyes - pharmacokinetics
Glycolysis
Humans
Indoles - chemistry
Indoles - pharmacokinetics
Iodides - chemistry
Iodides - pharmacokinetics
IR-780 iodide
Mechlorethamine - chemistry
Mechlorethamine - pharmacokinetics
Membrane Potential, Mitochondrial
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Neoplasm Transplantation
Nitrogen mustard
OATP1B3
Organic Anion Transporters - metabolism
Plasma membrane potential
Rats
Rats, Sprague-Dawley
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.10.033