title: IR-780 Dye as a Sonosensitizer for Sonodynamic Therapy of Breast Tumor.
abstract: Sonodynamic therapy (SDT) has become a new modality for cancer therapy through activating certain chemical sensitizers by ultrasound (US). Discovery and development of novel sonosensitizers are attracting extensive attentions. Here, we introduce IR-780 iodide, a lipophilic heptamethine dye with a peak optical absorption of 780 nm wavelength, which can function as SDT agents for breast cancer treatment. The in vitro cellular uptake, cell viability, and the generation levels of reactive oxygen species (ROS) were examined by using 4T1 breast cancer cells incubated with various concentrations of IR-780 followed by US irradiation. Our results showed a dose- and time-dependent cellular uptake of IR-780 iodide in 4T1 cancer cells. Significant lower viabilities and more necrotic/apoptotic cells were found when these cancer cells were treated with IR-780 iodide with US irradiation. Further analyzing the generation of ROS demonstrated significant increase of (1)O2 level and H2O2, but not ⋅OH in the SDT-treated cells. The in vivo anti-tumor efficacy of SDT with IR-780 revealed significant tumor growth inhibition of xenografts of 4T1 cancer cells; it was further confirmed by histological analysis and TUNEL staining. Our results strongly suggest that SDT combined with IR-780 may provide a promising strategy for tumor treatment with minimal side effects.
authors.affiliation: Department of Ultrasound, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
authors.forename: Yekuo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Zhiting
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physics, University of Vermont, Burlington, VT 5405-0160, USA.
authors.forename: Junru
authors.initials: J
authors.lastname: Wu
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.|Shenzhen Key Laboratory of Nanobiomechanics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014464:Ultrasonic Therapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
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; D007211:Indoles; D017382:Reactive Oxygen Species