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Preferential accumulation of the near infrared heptamethine dye IR-780 in the mitochondria of drug-resistant lung cancer cells.

Abstract
Personalized oncology significantly relies on the development of theranostic agents to integrate cancer therapeutics and diagnostics. Current strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer specific ligands, contrast agents and therapeutic drugs. In this study, we reported a near infrared (NIR) heptamethine indocyanine dye, IR-780, which selectively accumulated in the mitochondria of drug-resistant human lung cancer cells (A549/DR) and significantly inhibited cell growth, self-renewal and migration without the need of any chemical conjugation. IR-780 was also able to induce A549/DR cell apoptosis by disrupting the mitochondrial function. Furthermore, IR-780 dye exhibited remarkable tumoricidal activity and inhibited tumor recurrence in mouse syngeneic Lewis lung carcinoma xenograft model. With the unique properties of targeting, near infrared imaging and inhibitive effect to the drug-resistant cancer cells both in vitro and in vivo, IR-780 may represent a potential theranostic agent for tumor recurrence.
AuthorsYang Wang, Tao Liu, Erlong Zhang, Shenglin Luo, Xu Tan, Chunmeng Shi
JournalBiomaterials (Biomaterials) Vol. 35 Issue 13 Pg. 4116-24 (Apr 2014) ISSN: 1878-5905 [Electronic] Netherlands
PMID24529902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • 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
  • Antineoplastic Agents
  • Indoles
Topics
  • Animals
  • Antineoplastic Agents (pharmacokinetics, therapeutic use)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Humans
  • Indoles (pharmacokinetics, therapeutic use)
  • Lung Neoplasms (drug therapy)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria (metabolism)
  • Xenograft Model Antitumor Assays

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