In the mouse caudal thrombosis model, Pkr(IR-Ca/Pda-uPA)-cRGD exhibited efficient targeting and penetration capacity to thrombus substrates to considerably eradicate tail venous thrombi (approximately 1.61 cm) and decreased the unintentional bleeding complications; additionally, the rat DVT model further confirmed that targeted thrombolysis was successfully visualized by NIR-II FLI in minutes, enabling real-time monitoring of thrombus ablation to avoid overtreatment and undertreatment risks. The gene discussed is PLAU; the disease is deep vein thrombosis.