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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 1O2 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.
Highlights
Sonodynamic therapy (SDT) first discovered by Yumita et al.[1], which utilizes low intensity ultrasound (US) to activate a group of photosensitive materials called sonosensitizer and to enhance their cytotoxic effects to targeted cells, is emerging as a promising cancer treatment therapy[2]
The results demonstrated that IR-780 plus US induced significant tumor cell apoptosis/necrosis compared with the control groups (Fig. 3B–F)
We found the remarkable toxicity of SDT using IR-780 as a sonosensitizer against 4T1 breast cancer in vitro and in vivo
Summary
Sonodynamic therapy (SDT) first discovered by Yumita et al.[1], which utilizes low intensity ultrasound (US) to activate a group of photosensitive materials called sonosensitizer and to enhance their cytotoxic effects to targeted cells, is emerging as a promising cancer treatment therapy[2]. The received energy by sonosensitizers would be released when they return to the ground state from the excited state Oxygen molecules, when they acquire the released energy, will change into excited-singlet-state oxygens (a highly reactive agent) and initiate a series of oxidization reactions which eventually lead to the irreparable cellular damage[9]; (iv) ultrasound-induced apoptosis, i.e., the programmed death pathway will be activated when enough reactive oxygen species (ROS) are generated in tumor cells by US irradiation[10,11,12,13]. It is the first report about the application of SDT using IR-780 as a sonosensitizer for treatment of breast cancer
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