NIR laser-induced photothermal therapy (PTT) through near-infrared agents has demonstrated the great potential in solid tumor ablation. However, the nonuniform heat distribution over tumors from PTT makes it insufficient to kill all tumor cells, resulting in tumor recurrence and inferior outcomes. To improve the tumor treatment efficacy, it is highly desirable to develop the combinational treatment of PTT with other modalities, especially with chemotherapeutic agents. Here we report a smart DOX/IR-780-loaded temperature-sensitive-liposome (DITSL) which can achieve NIR-laser-controlled drug release for chemo-photothermal synergistic tumor therapy. In this system, the liposoluble IR-780 was incorporated into the temperature-sensitive lipid bilayer and the soluble chemotherapeutic doxorubicin (DOX) was encapsulated in the hydrophilic core. The resulting DITSL is proved to be physiologically stable and can provide a fast and laser irradiation-controllable DOX release in the PBS and cellular conditions. We further employed this nanoparticle for tumor treatment, demonstrating significantly higher tumor inhibition efficacy than that of DOX-loaded temperature-sensitive-liposome (DTSL) or IR780-loaded temperature-sensitive-liposome (ITSL) in the in vitro cells and in vivo animals. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of DITSL over DTSL or ITSL. Our study provides a promising strategy to realize chemo-photothermal synergistic combination therapy for breast tumors.
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.
Background:The effect of an early short-term home-based cardiac rehabilitation (CR) program on ventricular function in acute myocardial infarction (AMI) patients is not yet clear. The purpose of this study was to evaluate the efficacy of our CR program on the improvement of myocardial function using three-dimensional speckle tracking echocardiography (3D-STE) in AMI patients.Methods:Fifty-two AMI patients were randomly assigned to 2 groups after discharge: the rehabilitation group, which participated in an early, home-based CR program, and the control group, which received only usual care. All subjects in both groups underwent 3D-STE examinations of the left ventricle within 48 hours of percutaneous coronary intervention and again 4 weeks after discharge. Global longitudinal strain (GLS), global radial strain (GRS), global area strain (GAS), global circumferential strain (GCS), left ventricular ejection fraction (LVEF), and segmental strains were computed. The CR program was initially conducted with supervised inpatient training, followed by an unsupervised home-based training program during a 4-week follow-up.Results:We obtained segmental strains from 832 segments, of which 319 were defined as interventional segments, 179 as ischemic segments, and the remaining segments as normal segments. At the 4-week follow-up, when controlling for baseline values, the rehabilitation group showed significant improvements in GLS, GRS, GCS, GAS, LVEF, and in all of the segmental strains of the 3 subgroups compared with the control group (P <0.05).Conclusion:Our study suggests that an early, home-based CR program can greatly improve the ventricular function of AMI patients in a short period of time.
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