Massive hemorrhage caused by injuries and surgical procedures is a major challenge in emergency medical scenarios. Conventional means of hemostasis often fail to rapidly and efficiently control bleeding, especially in inaccessible locations. Herein, a type of smart nanoliposome with ultrasonic responsiveness, loaded with thrombin (thrombin@liposome, named TNL) was developed to serve as an efficient and rapid hemostatic agent. Firstly, the hydrophilic cavities of the liposomes were loaded onto the sono-sensitive agent protoporphyrin. Secondly, a singlet oxygen-sensitive chemical bond was connected with the hydrophobic and hydrophilic ends of liposomes in a chemical bond manner. Finally, based on the host guest effect between ultrasound and the sono-sensitizer, singlet oxygen is continuously generated, which breaks the hydrophobic and hydrophilic ends of liposome fragments, causing spatial collapse of the TNL structure, swiftly releases thrombin loaded in the hydrophilic capsule cavity, thereby achieving accurate and rapid local hemostasis (resulted in a reduction of approximately 67% in bleeding in the rat hemorrhage model). More importantly, after thorough assessments of biocompatibility and biodegradability, it has been confirmed that TNL possesses excellent biosafety, providing a new avenue for efficient and precise hemostasis.
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