Fluorescent probes with fluorescence emission in the NIR-II window have been widely studied due to increased imaging depth. However, the currently reported NIR-II fluorescent probes present some disadvantages, such as complicated synthesis routes and low fluorescence quantum yields (QYs). The shielding strategy has been used in the development of NIR-II probes to improve their QYs. So far, this strategy has only been used for the symmetric NIR-II probes, especially those based on the benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBTD) skeleton. This work reports the synthesis of a series of asymmetric NIR-II probes based on shielding strategies accompanied by simple synthetic routes, high synthetic yields (above 90%), high QYs, and large Stoke shifts. Furthermore, the use of d-α-tocopheryl polyethylene glycol succinate (TPGS) as a surfactant for an NIR-II fluorescence probe (NT-4) improved its water solubility. In vivo studies showed that TPGS-NT-4 NPs with a high QY (3.46%) achieve high-resolution angiography and efficient local photothermal therapy, while displaying good biocompatibility. Hence, we combined angiography and local photothermal therapy to improve the tumor uptake of nanophotothermal agents while reducing their damage to normal tissues.